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Study reveals racial disparities in advanced HF therapies
A new study shows that Black Americans received ventricular assist devices (VADs) and heart transplants about half as often as White Americans, even when receiving care at an advanced heart failure (HF) center.
The analysis, drawn from 377 patients treated at one of 21 VAD centers in the United States as part of the RIVIVAL study, found that 22.3% of White adults received a heart transplant or VAD, compared with 11% of Black adults.
“That’s what is so concerning to us, that we’re seeing this pattern within this select population. I think it would be too reasonable to hypothesize that it very well could be worse in the general population,” study author Thomas Cascino, MD, MSc, University of Michigan, Ann Arbor, commented.
The study was published online in Circulation: Heart Failure, and it builds on previous work by the researchers, showing that patient preference for early VAD therapy is associated with higher New York Heart Association (NYHA) class and lower income level but not race.
In the present analysis, the number of Black and White participants who said they “definitely or probably” wanted VAD therapy was similar (27% vs. 29%), as was the number wanting “any and all life-sustaining therapies” (74% vs. 65%).
Two-thirds of the cohort was NYHA class III, the average EuroQoL visual analog scale (EQ-VAS) score was 64.6 among the 100 participants who identified as Black and 62.1 in the 277 White participants, and the average age was 58 and 61 years, respectively.
Death rates were also similar during the 2-year follow-up: 18% of Black patients and 13% of White patients.
After controlling for multiple clinical and social determinants of health, including age, Interagency Registry for Mechanically Assisted Circulator Support (INTERMACS) patient profile, EQ-VAS score, and level of education, Black participants had a 55% lower rate of VAD or transplant, compared with White participants (hazard ratio, 0.45; 95% confidence interval, 0.23-0.85). Adding VAD preference to the model did not affect the association.
“Our study suggests that we as providers may be making decisions differently,” Dr. Cascino said. “We can’t say for sure what the reasons are but certainly structural racism, discrimination, and provider biases are the things I worry about.”
“There’s an absolute need for us to look inwards, reflect, and acknowledge that we are likely playing a role in this and then start to be part of the change,” he added.
“The lives disabled or lost are simply too many,” coauthor Wendy Taddei-Peters, PhD, a clinical trials project official at the National Heart, Lung, and Blood Institute, said in an NIH statement. “An immediate step could be to require implicit bias training, particularly for transplant and VAD team members.”
Other suggestions are better tracking of underserved patients and the reasons why they do not receive VAD or become listed for transplant; inclusion of psychosocial components into decision-making about advanced therapy candidacy; and having “disparity experts” join in heart team meetings to help identify biases in real time.
Commenting on the study, Khadijah Breathett, MD, HF/transplant cardiologist and tenured associate professor of medicine, Indiana University Bloomington, said, “I’m glad there’s more push for awareness, because there’s still a population of people that don’t believe this is a real problem.”
Dr. Breathett, who is also a racial equity researcher, noted that the findings are similar to those of multiple studies suggesting racial disparities in HF care. In her own 2019 study of 400 providers shown identical clinical vignettes except for race, survey results and think-aloud interviews showed that decisions about advanced HF therapies are hierarchal and not democratic, social history and adherence are the most influential factors, and Black men are seen as not trustworthy and adherent, despite identical social histories, which ultimately led to White men being offered transplantation and Black men VAD implantation. The bias was particularly evident among older providers.
“This problem is real,” Dr. Breathett said. “The process of allocating life-saving therapies is not fair, and there is some level of discrimination that’s taking place towards persons of color, particularly Black patients. It’s time that we consider how we fix these issues.”
To see whether centers can move the needle and put systemic level changes into practice, Dr. Breathett and colleagues are launching the Seeking Objectivity in Allocation of Advanced Heart Failure (SOCIAL HF) Therapies Trial at 14 sites in the United States. It will measure the number of minority and female patients receiving advanced HF therapies at centers randomized to usual care or HF training, including evidence-based bias reduction training, use of objective measures of social support, and changes to facilitate group dynamics. The trial is set to start in January and be completed in September 2026.
“The main takeaway from this study is that it highlights and re-highlights the fact that racial disparities do exist in access to advanced therapy care,” Jaimin Trivedi, MD, MPH, associate professor of cardiothoracic surgery and director of clinical research and bioinformatics, University of Louisville, Ky., said in an interview.
He also called for education and training for all professionals, not just during residency or fellowship, to specifically identify issues with Black patients and encourage Black patients and their family members to get more involved in their HF care.
Dr. Trivedi said that further studies should examine why death rates were similar in the study despite the observed disparities in VAD implantation and transplantation.
He also pointed out that while patients in the study were treated from July 2015 to June 2016, a recent analysis by his team of the United Network for Organ Sharing (UNOS) database showed that 26% of transplants in 2019 were among Black patients, up from just 5% in 1987. “So, there are some encouraging signs as well.”
The study was funded by the National Institutes of Health/National Heart, Lung, and Blood Institute (NHLBI) and the National Center for Advancing Translational Sciences. Dr. Cascino reports having no relevant financial relationships. Four coauthors report financial relationships, including David Lanfear, who serves on the advisory board at Medscape. Dr. Breathett reported funding from multiple NHLBI grants.
A version of this article first appeared on Medscape.com.
A new study shows that Black Americans received ventricular assist devices (VADs) and heart transplants about half as often as White Americans, even when receiving care at an advanced heart failure (HF) center.
The analysis, drawn from 377 patients treated at one of 21 VAD centers in the United States as part of the RIVIVAL study, found that 22.3% of White adults received a heart transplant or VAD, compared with 11% of Black adults.
“That’s what is so concerning to us, that we’re seeing this pattern within this select population. I think it would be too reasonable to hypothesize that it very well could be worse in the general population,” study author Thomas Cascino, MD, MSc, University of Michigan, Ann Arbor, commented.
The study was published online in Circulation: Heart Failure, and it builds on previous work by the researchers, showing that patient preference for early VAD therapy is associated with higher New York Heart Association (NYHA) class and lower income level but not race.
In the present analysis, the number of Black and White participants who said they “definitely or probably” wanted VAD therapy was similar (27% vs. 29%), as was the number wanting “any and all life-sustaining therapies” (74% vs. 65%).
Two-thirds of the cohort was NYHA class III, the average EuroQoL visual analog scale (EQ-VAS) score was 64.6 among the 100 participants who identified as Black and 62.1 in the 277 White participants, and the average age was 58 and 61 years, respectively.
Death rates were also similar during the 2-year follow-up: 18% of Black patients and 13% of White patients.
After controlling for multiple clinical and social determinants of health, including age, Interagency Registry for Mechanically Assisted Circulator Support (INTERMACS) patient profile, EQ-VAS score, and level of education, Black participants had a 55% lower rate of VAD or transplant, compared with White participants (hazard ratio, 0.45; 95% confidence interval, 0.23-0.85). Adding VAD preference to the model did not affect the association.
“Our study suggests that we as providers may be making decisions differently,” Dr. Cascino said. “We can’t say for sure what the reasons are but certainly structural racism, discrimination, and provider biases are the things I worry about.”
“There’s an absolute need for us to look inwards, reflect, and acknowledge that we are likely playing a role in this and then start to be part of the change,” he added.
“The lives disabled or lost are simply too many,” coauthor Wendy Taddei-Peters, PhD, a clinical trials project official at the National Heart, Lung, and Blood Institute, said in an NIH statement. “An immediate step could be to require implicit bias training, particularly for transplant and VAD team members.”
Other suggestions are better tracking of underserved patients and the reasons why they do not receive VAD or become listed for transplant; inclusion of psychosocial components into decision-making about advanced therapy candidacy; and having “disparity experts” join in heart team meetings to help identify biases in real time.
Commenting on the study, Khadijah Breathett, MD, HF/transplant cardiologist and tenured associate professor of medicine, Indiana University Bloomington, said, “I’m glad there’s more push for awareness, because there’s still a population of people that don’t believe this is a real problem.”
Dr. Breathett, who is also a racial equity researcher, noted that the findings are similar to those of multiple studies suggesting racial disparities in HF care. In her own 2019 study of 400 providers shown identical clinical vignettes except for race, survey results and think-aloud interviews showed that decisions about advanced HF therapies are hierarchal and not democratic, social history and adherence are the most influential factors, and Black men are seen as not trustworthy and adherent, despite identical social histories, which ultimately led to White men being offered transplantation and Black men VAD implantation. The bias was particularly evident among older providers.
“This problem is real,” Dr. Breathett said. “The process of allocating life-saving therapies is not fair, and there is some level of discrimination that’s taking place towards persons of color, particularly Black patients. It’s time that we consider how we fix these issues.”
To see whether centers can move the needle and put systemic level changes into practice, Dr. Breathett and colleagues are launching the Seeking Objectivity in Allocation of Advanced Heart Failure (SOCIAL HF) Therapies Trial at 14 sites in the United States. It will measure the number of minority and female patients receiving advanced HF therapies at centers randomized to usual care or HF training, including evidence-based bias reduction training, use of objective measures of social support, and changes to facilitate group dynamics. The trial is set to start in January and be completed in September 2026.
“The main takeaway from this study is that it highlights and re-highlights the fact that racial disparities do exist in access to advanced therapy care,” Jaimin Trivedi, MD, MPH, associate professor of cardiothoracic surgery and director of clinical research and bioinformatics, University of Louisville, Ky., said in an interview.
He also called for education and training for all professionals, not just during residency or fellowship, to specifically identify issues with Black patients and encourage Black patients and their family members to get more involved in their HF care.
Dr. Trivedi said that further studies should examine why death rates were similar in the study despite the observed disparities in VAD implantation and transplantation.
He also pointed out that while patients in the study were treated from July 2015 to June 2016, a recent analysis by his team of the United Network for Organ Sharing (UNOS) database showed that 26% of transplants in 2019 were among Black patients, up from just 5% in 1987. “So, there are some encouraging signs as well.”
The study was funded by the National Institutes of Health/National Heart, Lung, and Blood Institute (NHLBI) and the National Center for Advancing Translational Sciences. Dr. Cascino reports having no relevant financial relationships. Four coauthors report financial relationships, including David Lanfear, who serves on the advisory board at Medscape. Dr. Breathett reported funding from multiple NHLBI grants.
A version of this article first appeared on Medscape.com.
A new study shows that Black Americans received ventricular assist devices (VADs) and heart transplants about half as often as White Americans, even when receiving care at an advanced heart failure (HF) center.
The analysis, drawn from 377 patients treated at one of 21 VAD centers in the United States as part of the RIVIVAL study, found that 22.3% of White adults received a heart transplant or VAD, compared with 11% of Black adults.
“That’s what is so concerning to us, that we’re seeing this pattern within this select population. I think it would be too reasonable to hypothesize that it very well could be worse in the general population,” study author Thomas Cascino, MD, MSc, University of Michigan, Ann Arbor, commented.
The study was published online in Circulation: Heart Failure, and it builds on previous work by the researchers, showing that patient preference for early VAD therapy is associated with higher New York Heart Association (NYHA) class and lower income level but not race.
In the present analysis, the number of Black and White participants who said they “definitely or probably” wanted VAD therapy was similar (27% vs. 29%), as was the number wanting “any and all life-sustaining therapies” (74% vs. 65%).
Two-thirds of the cohort was NYHA class III, the average EuroQoL visual analog scale (EQ-VAS) score was 64.6 among the 100 participants who identified as Black and 62.1 in the 277 White participants, and the average age was 58 and 61 years, respectively.
Death rates were also similar during the 2-year follow-up: 18% of Black patients and 13% of White patients.
After controlling for multiple clinical and social determinants of health, including age, Interagency Registry for Mechanically Assisted Circulator Support (INTERMACS) patient profile, EQ-VAS score, and level of education, Black participants had a 55% lower rate of VAD or transplant, compared with White participants (hazard ratio, 0.45; 95% confidence interval, 0.23-0.85). Adding VAD preference to the model did not affect the association.
“Our study suggests that we as providers may be making decisions differently,” Dr. Cascino said. “We can’t say for sure what the reasons are but certainly structural racism, discrimination, and provider biases are the things I worry about.”
“There’s an absolute need for us to look inwards, reflect, and acknowledge that we are likely playing a role in this and then start to be part of the change,” he added.
“The lives disabled or lost are simply too many,” coauthor Wendy Taddei-Peters, PhD, a clinical trials project official at the National Heart, Lung, and Blood Institute, said in an NIH statement. “An immediate step could be to require implicit bias training, particularly for transplant and VAD team members.”
Other suggestions are better tracking of underserved patients and the reasons why they do not receive VAD or become listed for transplant; inclusion of psychosocial components into decision-making about advanced therapy candidacy; and having “disparity experts” join in heart team meetings to help identify biases in real time.
Commenting on the study, Khadijah Breathett, MD, HF/transplant cardiologist and tenured associate professor of medicine, Indiana University Bloomington, said, “I’m glad there’s more push for awareness, because there’s still a population of people that don’t believe this is a real problem.”
Dr. Breathett, who is also a racial equity researcher, noted that the findings are similar to those of multiple studies suggesting racial disparities in HF care. In her own 2019 study of 400 providers shown identical clinical vignettes except for race, survey results and think-aloud interviews showed that decisions about advanced HF therapies are hierarchal and not democratic, social history and adherence are the most influential factors, and Black men are seen as not trustworthy and adherent, despite identical social histories, which ultimately led to White men being offered transplantation and Black men VAD implantation. The bias was particularly evident among older providers.
“This problem is real,” Dr. Breathett said. “The process of allocating life-saving therapies is not fair, and there is some level of discrimination that’s taking place towards persons of color, particularly Black patients. It’s time that we consider how we fix these issues.”
To see whether centers can move the needle and put systemic level changes into practice, Dr. Breathett and colleagues are launching the Seeking Objectivity in Allocation of Advanced Heart Failure (SOCIAL HF) Therapies Trial at 14 sites in the United States. It will measure the number of minority and female patients receiving advanced HF therapies at centers randomized to usual care or HF training, including evidence-based bias reduction training, use of objective measures of social support, and changes to facilitate group dynamics. The trial is set to start in January and be completed in September 2026.
“The main takeaway from this study is that it highlights and re-highlights the fact that racial disparities do exist in access to advanced therapy care,” Jaimin Trivedi, MD, MPH, associate professor of cardiothoracic surgery and director of clinical research and bioinformatics, University of Louisville, Ky., said in an interview.
He also called for education and training for all professionals, not just during residency or fellowship, to specifically identify issues with Black patients and encourage Black patients and their family members to get more involved in their HF care.
Dr. Trivedi said that further studies should examine why death rates were similar in the study despite the observed disparities in VAD implantation and transplantation.
He also pointed out that while patients in the study were treated from July 2015 to June 2016, a recent analysis by his team of the United Network for Organ Sharing (UNOS) database showed that 26% of transplants in 2019 were among Black patients, up from just 5% in 1987. “So, there are some encouraging signs as well.”
The study was funded by the National Institutes of Health/National Heart, Lung, and Blood Institute (NHLBI) and the National Center for Advancing Translational Sciences. Dr. Cascino reports having no relevant financial relationships. Four coauthors report financial relationships, including David Lanfear, who serves on the advisory board at Medscape. Dr. Breathett reported funding from multiple NHLBI grants.
A version of this article first appeared on Medscape.com.
New deep dive into Paxlovid interactions with CVD meds
Nirmatrelvir/ritonavir (Paxlovid) has been a game changer for high-risk patients with early COVID-19 symptoms but has significant interactions with commonly used cardiovascular medications, a new paper cautions.
COVID-19 patients with cardiovascular disease (CVD) or risk factors such as diabetes, hypertension, and chronic kidney disease are at high risk of severe disease and account for the lion’s share of those receiving Paxlovid. Data from the initial EPIC-HR trial and recent real-world data also suggest they’re among the most likely to benefit from the oral antiviral, regardless of their COVID-19 vaccination status.
“But at the same time, it unfortunately interacts with many very commonly prescribed cardiovascular medications and with many of them in a very clinically meaningful way, which may lead to serious adverse consequences,” senior author Sarju Ganatra, MD, said in an interview. “So, while it’s being prescribed with a good intention to help these people, we may actually end up doing more harm than good.
“We don’t want to deter people from getting their necessary COVID-19 treatment, which is excellent for the most part these days as an outpatient,” he added. “So, we felt the need to make a comprehensive list of cardiac medications and level of interactions with Paxlovid and also to help the clinicians and prescribers at the point of care to make the clinical decision of what modifications they may need to do.”
The paper, published online in the Journal of the American College of Cardiology, details drug-drug interactions with some 80 CV medications including statins, antihypertensive agents, heart failure therapies, and antiplatelet/anticoagulants.
It also includes a color-coded figure denoting whether a drug is safe to coadminister with Paxlovid, may potentially interact and require a dose adjustment or temporary discontinuation, or is contraindicated.
Among the commonly used blood thinners, for example, the paper notes that Paxlovid significantly increases drug levels of the direct oral anticoagulants (DOACs) apixaban, rivaroxaban, edoxaban, and dabigatran and, thus, increases the risk of bleeding.
“It can still be administered, if it’s necessary, but the dose of the DOAC either needs to be reduced or held depending on what they are getting it for, whether they’re getting it for pulmonary embolism or atrial fibrillation, and we adjust for all those things in the table in the paper,” said Dr. Ganatra, from Lahey Hospital and Medical Center, Burlington, Mass.
When the DOAC can’t be interrupted or dose adjusted, however, Paxlovid should not be given, the experts said. The antiviral is safe to use with enoxaparin, a low-molecular-weight heparin, but can increase or decrease levels of warfarin and should be used with close international normalized ratio monitoring.
For patients on antiplatelet agents, clinicians are advised to avoid prescribing nirmatrelvir/ritonavir to those on ticagrelor or clopidogrel unless the agents can be replaced by prasugrel.
Ritonavir – an inhibitor of cytochrome P 450 enzymes, particularly CYP3A4 – poses an increased risk of bleeding when given with ticagrelor, a CYP3A4 substrate, and decreases the active metabolite of clopidogrel, cutting its platelet inhibition by 20%. Although there’s a twofold decrease in the maximum concentration of prasugrel in patients on ritonavir, this does not affect its antiplatelet activity, the paper explains.
Among the lipid-lowering agents, experts suggested temporarily withholding atorvastatin, rosuvastatin, simvastatin, and lovastatin because of an increased risk for myopathy and liver toxicity but say that other statins, fibrates, ezetimibe, and the proprotein convertase subtilisin/kexin type 9 inhibitors evolocumab and alirocumab are safe to coadminister with Paxlovid.
While statins typically leave the body within hours, most of the antiarrhythmic drugs, except for sotalol, are not safe to give with Paxlovid, Dr. Ganatra said. It’s technically not feasible to hold these drugs because most have long half-lives, reaching about 100 days, for example, for amiodarone.
“It’s going to hang around in your system for a long time, so you don’t want to be falsely reassured that you’re holding the drug and it’s going to be fine to go back slowly,” he said. “You need to look for alternative therapies in those scenarios for COVID-19 treatment, which could be other antivirals, or a monoclonal antibody individualized to the patient’s risk.”
Although there’s limited clinical information regarding interaction-related adverse events with Paxlovid, the team used pharmacokinetics and pharmacodynamics data to provide the guidance. Serious adverse events are also well documented for ritonavir, which has been prescribed for years to treat HIV, Dr. Ganatra noted.
The Infectious Disease Society of America also published guidance on the management of potential drug interactions with Paxlovid in May and, earlier in October, the Food and Drug Administration updated its Paxlovid patient eligibility screening checklist.
Still, most prescribers are actually primary care physicians and even pharmacists, who may not be completely attuned, said Dr. Ganatra, who noted that some centers have started programs to help connect primary care physicians with their cardiology colleagues to check on CV drugs in their COVID-19 patients.
“We need to be thinking more broadly and at a system level where the hospital or health care system leverages the electronic health record systems,” he said. “Most of them are sophisticated enough to incorporate simple drug-drug interaction information, so if you try to prescribe someone Paxlovid and it’s a heart transplant patient who is on immunosuppressive therapy or a patient on a blood thinner, then it should give you a warning ... or at least give them a link to our paper or other valuable resources.
“If someone is on a blood thinner and the blood thinner level goes up by ninefold, we can only imagine what we would be dealing with,” Dr. Ganatra said. “So, these interactions should be taken very seriously and I think it’s worth the time and investment.”
The authors reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Nirmatrelvir/ritonavir (Paxlovid) has been a game changer for high-risk patients with early COVID-19 symptoms but has significant interactions with commonly used cardiovascular medications, a new paper cautions.
COVID-19 patients with cardiovascular disease (CVD) or risk factors such as diabetes, hypertension, and chronic kidney disease are at high risk of severe disease and account for the lion’s share of those receiving Paxlovid. Data from the initial EPIC-HR trial and recent real-world data also suggest they’re among the most likely to benefit from the oral antiviral, regardless of their COVID-19 vaccination status.
“But at the same time, it unfortunately interacts with many very commonly prescribed cardiovascular medications and with many of them in a very clinically meaningful way, which may lead to serious adverse consequences,” senior author Sarju Ganatra, MD, said in an interview. “So, while it’s being prescribed with a good intention to help these people, we may actually end up doing more harm than good.
“We don’t want to deter people from getting their necessary COVID-19 treatment, which is excellent for the most part these days as an outpatient,” he added. “So, we felt the need to make a comprehensive list of cardiac medications and level of interactions with Paxlovid and also to help the clinicians and prescribers at the point of care to make the clinical decision of what modifications they may need to do.”
The paper, published online in the Journal of the American College of Cardiology, details drug-drug interactions with some 80 CV medications including statins, antihypertensive agents, heart failure therapies, and antiplatelet/anticoagulants.
It also includes a color-coded figure denoting whether a drug is safe to coadminister with Paxlovid, may potentially interact and require a dose adjustment or temporary discontinuation, or is contraindicated.
Among the commonly used blood thinners, for example, the paper notes that Paxlovid significantly increases drug levels of the direct oral anticoagulants (DOACs) apixaban, rivaroxaban, edoxaban, and dabigatran and, thus, increases the risk of bleeding.
“It can still be administered, if it’s necessary, but the dose of the DOAC either needs to be reduced or held depending on what they are getting it for, whether they’re getting it for pulmonary embolism or atrial fibrillation, and we adjust for all those things in the table in the paper,” said Dr. Ganatra, from Lahey Hospital and Medical Center, Burlington, Mass.
When the DOAC can’t be interrupted or dose adjusted, however, Paxlovid should not be given, the experts said. The antiviral is safe to use with enoxaparin, a low-molecular-weight heparin, but can increase or decrease levels of warfarin and should be used with close international normalized ratio monitoring.
For patients on antiplatelet agents, clinicians are advised to avoid prescribing nirmatrelvir/ritonavir to those on ticagrelor or clopidogrel unless the agents can be replaced by prasugrel.
Ritonavir – an inhibitor of cytochrome P 450 enzymes, particularly CYP3A4 – poses an increased risk of bleeding when given with ticagrelor, a CYP3A4 substrate, and decreases the active metabolite of clopidogrel, cutting its platelet inhibition by 20%. Although there’s a twofold decrease in the maximum concentration of prasugrel in patients on ritonavir, this does not affect its antiplatelet activity, the paper explains.
Among the lipid-lowering agents, experts suggested temporarily withholding atorvastatin, rosuvastatin, simvastatin, and lovastatin because of an increased risk for myopathy and liver toxicity but say that other statins, fibrates, ezetimibe, and the proprotein convertase subtilisin/kexin type 9 inhibitors evolocumab and alirocumab are safe to coadminister with Paxlovid.
While statins typically leave the body within hours, most of the antiarrhythmic drugs, except for sotalol, are not safe to give with Paxlovid, Dr. Ganatra said. It’s technically not feasible to hold these drugs because most have long half-lives, reaching about 100 days, for example, for amiodarone.
“It’s going to hang around in your system for a long time, so you don’t want to be falsely reassured that you’re holding the drug and it’s going to be fine to go back slowly,” he said. “You need to look for alternative therapies in those scenarios for COVID-19 treatment, which could be other antivirals, or a monoclonal antibody individualized to the patient’s risk.”
Although there’s limited clinical information regarding interaction-related adverse events with Paxlovid, the team used pharmacokinetics and pharmacodynamics data to provide the guidance. Serious adverse events are also well documented for ritonavir, which has been prescribed for years to treat HIV, Dr. Ganatra noted.
The Infectious Disease Society of America also published guidance on the management of potential drug interactions with Paxlovid in May and, earlier in October, the Food and Drug Administration updated its Paxlovid patient eligibility screening checklist.
Still, most prescribers are actually primary care physicians and even pharmacists, who may not be completely attuned, said Dr. Ganatra, who noted that some centers have started programs to help connect primary care physicians with their cardiology colleagues to check on CV drugs in their COVID-19 patients.
“We need to be thinking more broadly and at a system level where the hospital or health care system leverages the electronic health record systems,” he said. “Most of them are sophisticated enough to incorporate simple drug-drug interaction information, so if you try to prescribe someone Paxlovid and it’s a heart transplant patient who is on immunosuppressive therapy or a patient on a blood thinner, then it should give you a warning ... or at least give them a link to our paper or other valuable resources.
“If someone is on a blood thinner and the blood thinner level goes up by ninefold, we can only imagine what we would be dealing with,” Dr. Ganatra said. “So, these interactions should be taken very seriously and I think it’s worth the time and investment.”
The authors reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Nirmatrelvir/ritonavir (Paxlovid) has been a game changer for high-risk patients with early COVID-19 symptoms but has significant interactions with commonly used cardiovascular medications, a new paper cautions.
COVID-19 patients with cardiovascular disease (CVD) or risk factors such as diabetes, hypertension, and chronic kidney disease are at high risk of severe disease and account for the lion’s share of those receiving Paxlovid. Data from the initial EPIC-HR trial and recent real-world data also suggest they’re among the most likely to benefit from the oral antiviral, regardless of their COVID-19 vaccination status.
“But at the same time, it unfortunately interacts with many very commonly prescribed cardiovascular medications and with many of them in a very clinically meaningful way, which may lead to serious adverse consequences,” senior author Sarju Ganatra, MD, said in an interview. “So, while it’s being prescribed with a good intention to help these people, we may actually end up doing more harm than good.
“We don’t want to deter people from getting their necessary COVID-19 treatment, which is excellent for the most part these days as an outpatient,” he added. “So, we felt the need to make a comprehensive list of cardiac medications and level of interactions with Paxlovid and also to help the clinicians and prescribers at the point of care to make the clinical decision of what modifications they may need to do.”
The paper, published online in the Journal of the American College of Cardiology, details drug-drug interactions with some 80 CV medications including statins, antihypertensive agents, heart failure therapies, and antiplatelet/anticoagulants.
It also includes a color-coded figure denoting whether a drug is safe to coadminister with Paxlovid, may potentially interact and require a dose adjustment or temporary discontinuation, or is contraindicated.
Among the commonly used blood thinners, for example, the paper notes that Paxlovid significantly increases drug levels of the direct oral anticoagulants (DOACs) apixaban, rivaroxaban, edoxaban, and dabigatran and, thus, increases the risk of bleeding.
“It can still be administered, if it’s necessary, but the dose of the DOAC either needs to be reduced or held depending on what they are getting it for, whether they’re getting it for pulmonary embolism or atrial fibrillation, and we adjust for all those things in the table in the paper,” said Dr. Ganatra, from Lahey Hospital and Medical Center, Burlington, Mass.
When the DOAC can’t be interrupted or dose adjusted, however, Paxlovid should not be given, the experts said. The antiviral is safe to use with enoxaparin, a low-molecular-weight heparin, but can increase or decrease levels of warfarin and should be used with close international normalized ratio monitoring.
For patients on antiplatelet agents, clinicians are advised to avoid prescribing nirmatrelvir/ritonavir to those on ticagrelor or clopidogrel unless the agents can be replaced by prasugrel.
Ritonavir – an inhibitor of cytochrome P 450 enzymes, particularly CYP3A4 – poses an increased risk of bleeding when given with ticagrelor, a CYP3A4 substrate, and decreases the active metabolite of clopidogrel, cutting its platelet inhibition by 20%. Although there’s a twofold decrease in the maximum concentration of prasugrel in patients on ritonavir, this does not affect its antiplatelet activity, the paper explains.
Among the lipid-lowering agents, experts suggested temporarily withholding atorvastatin, rosuvastatin, simvastatin, and lovastatin because of an increased risk for myopathy and liver toxicity but say that other statins, fibrates, ezetimibe, and the proprotein convertase subtilisin/kexin type 9 inhibitors evolocumab and alirocumab are safe to coadminister with Paxlovid.
While statins typically leave the body within hours, most of the antiarrhythmic drugs, except for sotalol, are not safe to give with Paxlovid, Dr. Ganatra said. It’s technically not feasible to hold these drugs because most have long half-lives, reaching about 100 days, for example, for amiodarone.
“It’s going to hang around in your system for a long time, so you don’t want to be falsely reassured that you’re holding the drug and it’s going to be fine to go back slowly,” he said. “You need to look for alternative therapies in those scenarios for COVID-19 treatment, which could be other antivirals, or a monoclonal antibody individualized to the patient’s risk.”
Although there’s limited clinical information regarding interaction-related adverse events with Paxlovid, the team used pharmacokinetics and pharmacodynamics data to provide the guidance. Serious adverse events are also well documented for ritonavir, which has been prescribed for years to treat HIV, Dr. Ganatra noted.
The Infectious Disease Society of America also published guidance on the management of potential drug interactions with Paxlovid in May and, earlier in October, the Food and Drug Administration updated its Paxlovid patient eligibility screening checklist.
Still, most prescribers are actually primary care physicians and even pharmacists, who may not be completely attuned, said Dr. Ganatra, who noted that some centers have started programs to help connect primary care physicians with their cardiology colleagues to check on CV drugs in their COVID-19 patients.
“We need to be thinking more broadly and at a system level where the hospital or health care system leverages the electronic health record systems,” he said. “Most of them are sophisticated enough to incorporate simple drug-drug interaction information, so if you try to prescribe someone Paxlovid and it’s a heart transplant patient who is on immunosuppressive therapy or a patient on a blood thinner, then it should give you a warning ... or at least give them a link to our paper or other valuable resources.
“If someone is on a blood thinner and the blood thinner level goes up by ninefold, we can only imagine what we would be dealing with,” Dr. Ganatra said. “So, these interactions should be taken very seriously and I think it’s worth the time and investment.”
The authors reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM THE JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
Cardiac biomarkers track with hormone therapy in transgender people
Cardiac biomarkers vary according to sex hormones in healthy transgender adults, just as in cisgender individuals, a new cross-sectional study suggests.
Previous research in the general population has shown that females have a lower 99th percentile upper reference limit for high-sensitivity cardiac troponin (hs-cTn) than males, whereas N-terminal prohormone brain natriuretic peptide (NT-proBNP) concentrations are higher in females than males across all ages after puberty.
“That trend is similar for people that have been on gender-affirming hormones, saying that sex hormones are playing a role in how cardiac turnover happens in a healthy state,” study author Dina M. Greene, PhD, University of Washington, Seattle, said in an interview.
Although the number of transgender people seeking gender-affirming care is increasing, studies are limited and largely retrospective cohorts, she noted. The scientific literature evaluating and defining cardiac biomarker concentrations is “currently absent.”
The American Heart Association’s recent scientific statement on the cardiovascular health of transgender and gender diverse (TGD) people says mounting evidence points to worse CV health in TGD people and that part of this excess risk is driven by significant psychosocial stressors across the lifespan. “In addition, the use of gender-affirming hormone therapy may be associated with cardiometabolic changes, but health research in this area remains limited and, at times, contradictory.”
For the present study, Dr. Greene and colleagues reached out to LGBTQ-oriented primary care and internal medicine clinics in Seattle and Iowa City to recruit 79 transgender men prescribed testosterone (mean age, 28.8 years) and 93 transgender women (mean age, 35.1 years) prescribed estradiol for at least 12 months. The mean duration of hormone therapy was 4.8 and 3.5 years, respectively.
The median estradiol concentration was 51 pg/mL in transgender men and 207 pg/mL in transgender women. Median testosterone concentrations were 4.6 ng/mL and 0.4 ng/mL, respectively.
The cardiac biomarkers were measured with the ARCHITECT STAT (Abbott Diagnostics) and ACCESS (Beckman Coulter) high-sensitivity troponin I assays, the Elecsys Troponin T Gen 5 STAT assay (Roche Diagnostics), and the Elecsys ProBNP II immunoassay (Roche Diagnostics).
As reported in JAMA Cardiology, the median hs-cTnI level on the ARCHITECT STAT assay was 0.9 ng/L (range, 0.6-1.7) in transgender men and 0.6 ng/L (range, 0.3-1.0) in transgender women. The pattern was consistent across the two other assays.
In contrast, the median NT-proBNP level was 17 ng/L (range, 13-27) in transgender men and 49 ng/L (range, 32-86) in transgender women.
“It seems that sex hormone concentration is a stronger driver of baseline cardiac troponin and NT-proBNP concentrations relative to sex assigned at birth,” Dr. Greene said.
The observed differences in hs-cTn concentrations “are likely physiological and not pathological,” given that concentrations between healthy cisgender people are also apparent and not thought to portend adverse events, the authors noted.
Teasing out the clinical implications of sex-specific hs-cTn upper reference limits for ruling in acute myocardial infarction (MI), however, is complicated by biological and social factors that contribute to poorer outcomes in women, despite lower baseline levels, they added. “Ultimately, the psychosocial benefits of gender-affirming hormones are substantial, and informed consent is likely the ideal method to balance the undetermined risks.”
Dr. Greene pointed out that the study wasn’t powered to accurately calculate gender-specific hs-cTn 99th percentiles or reference intervals for NT-proBNP and assessed the biomarkers at a single time point.
For the transgender person presenting with chest pain, she said, the clinical implications are not yet known, but the data suggest that when sex-specific 99th percentiles for hs-cTn are used, the numeric value associated with the affirmed gender, rather than the sex assigned at birth, may be the appropriate URL.
“It really depends on what the triage pathway is and if that pathway has differences for people of different sexes and how often people get serial measurements,” Dr. Greene said. “Within this population, it’s very important to look at those serial measurements because for people that are not cismen, those 99th percentiles when they’re non–sex specific, are going to favor in detection of a heart attack. So, you need to look at the second value to make sure there hasn’t been a change over time.”
The observed differences in the distribution of NT-proBNP concentrations is similar to that in the cisgender population, Dr. Greene noted. But these differences do not lead to sex-specific diagnostic thresholds because of the significant elevations present in overt heart failure and cardiovascular disease. “For NT-proBNP, it’s not as important. People don’t usually have a little bit of heart failure, they have heart failure, where people have small MIs.”
Dr. Greene said she would like to see larger trials looking at biomarker measurements and cardiac imaging before hormone therapy but that the biggest issue is the need for inclusion of transgender people in all cardiovascular trials.
“The sample sizes are never going to be as big as we get for cisgender people for a number of reasons but ensuring that it’s something that’s being asked on intake and monitored over time so we can understand how transgender people fit into the general population for cardiac disease,” Dr. Greene said. “And so, we can normalize that they exist. I keep driving this point home, but this is the biggest thing right now when it’s such a political issue.”
The study was supported in part by the department of laboratory medicine at the University of Washington, the department of pathology at the University of Iowa, and a grant from Abbott Diagnostics for in-kind high-sensitivity cardiac troponin I reagent. One coauthor reported financial relationships with Siemens Healthineers, Roche Diagnostics, Beckman Coulter, Becton, Dickinson, Abbott Diagnostics, Quidel Diagnostics, Sphingotech, and PixCell Medical. No other disclosures were reported.
A version of this article first appeared on Medscape.com.
Cardiac biomarkers vary according to sex hormones in healthy transgender adults, just as in cisgender individuals, a new cross-sectional study suggests.
Previous research in the general population has shown that females have a lower 99th percentile upper reference limit for high-sensitivity cardiac troponin (hs-cTn) than males, whereas N-terminal prohormone brain natriuretic peptide (NT-proBNP) concentrations are higher in females than males across all ages after puberty.
“That trend is similar for people that have been on gender-affirming hormones, saying that sex hormones are playing a role in how cardiac turnover happens in a healthy state,” study author Dina M. Greene, PhD, University of Washington, Seattle, said in an interview.
Although the number of transgender people seeking gender-affirming care is increasing, studies are limited and largely retrospective cohorts, she noted. The scientific literature evaluating and defining cardiac biomarker concentrations is “currently absent.”
The American Heart Association’s recent scientific statement on the cardiovascular health of transgender and gender diverse (TGD) people says mounting evidence points to worse CV health in TGD people and that part of this excess risk is driven by significant psychosocial stressors across the lifespan. “In addition, the use of gender-affirming hormone therapy may be associated with cardiometabolic changes, but health research in this area remains limited and, at times, contradictory.”
For the present study, Dr. Greene and colleagues reached out to LGBTQ-oriented primary care and internal medicine clinics in Seattle and Iowa City to recruit 79 transgender men prescribed testosterone (mean age, 28.8 years) and 93 transgender women (mean age, 35.1 years) prescribed estradiol for at least 12 months. The mean duration of hormone therapy was 4.8 and 3.5 years, respectively.
The median estradiol concentration was 51 pg/mL in transgender men and 207 pg/mL in transgender women. Median testosterone concentrations were 4.6 ng/mL and 0.4 ng/mL, respectively.
The cardiac biomarkers were measured with the ARCHITECT STAT (Abbott Diagnostics) and ACCESS (Beckman Coulter) high-sensitivity troponin I assays, the Elecsys Troponin T Gen 5 STAT assay (Roche Diagnostics), and the Elecsys ProBNP II immunoassay (Roche Diagnostics).
As reported in JAMA Cardiology, the median hs-cTnI level on the ARCHITECT STAT assay was 0.9 ng/L (range, 0.6-1.7) in transgender men and 0.6 ng/L (range, 0.3-1.0) in transgender women. The pattern was consistent across the two other assays.
In contrast, the median NT-proBNP level was 17 ng/L (range, 13-27) in transgender men and 49 ng/L (range, 32-86) in transgender women.
“It seems that sex hormone concentration is a stronger driver of baseline cardiac troponin and NT-proBNP concentrations relative to sex assigned at birth,” Dr. Greene said.
The observed differences in hs-cTn concentrations “are likely physiological and not pathological,” given that concentrations between healthy cisgender people are also apparent and not thought to portend adverse events, the authors noted.
Teasing out the clinical implications of sex-specific hs-cTn upper reference limits for ruling in acute myocardial infarction (MI), however, is complicated by biological and social factors that contribute to poorer outcomes in women, despite lower baseline levels, they added. “Ultimately, the psychosocial benefits of gender-affirming hormones are substantial, and informed consent is likely the ideal method to balance the undetermined risks.”
Dr. Greene pointed out that the study wasn’t powered to accurately calculate gender-specific hs-cTn 99th percentiles or reference intervals for NT-proBNP and assessed the biomarkers at a single time point.
For the transgender person presenting with chest pain, she said, the clinical implications are not yet known, but the data suggest that when sex-specific 99th percentiles for hs-cTn are used, the numeric value associated with the affirmed gender, rather than the sex assigned at birth, may be the appropriate URL.
“It really depends on what the triage pathway is and if that pathway has differences for people of different sexes and how often people get serial measurements,” Dr. Greene said. “Within this population, it’s very important to look at those serial measurements because for people that are not cismen, those 99th percentiles when they’re non–sex specific, are going to favor in detection of a heart attack. So, you need to look at the second value to make sure there hasn’t been a change over time.”
The observed differences in the distribution of NT-proBNP concentrations is similar to that in the cisgender population, Dr. Greene noted. But these differences do not lead to sex-specific diagnostic thresholds because of the significant elevations present in overt heart failure and cardiovascular disease. “For NT-proBNP, it’s not as important. People don’t usually have a little bit of heart failure, they have heart failure, where people have small MIs.”
Dr. Greene said she would like to see larger trials looking at biomarker measurements and cardiac imaging before hormone therapy but that the biggest issue is the need for inclusion of transgender people in all cardiovascular trials.
“The sample sizes are never going to be as big as we get for cisgender people for a number of reasons but ensuring that it’s something that’s being asked on intake and monitored over time so we can understand how transgender people fit into the general population for cardiac disease,” Dr. Greene said. “And so, we can normalize that they exist. I keep driving this point home, but this is the biggest thing right now when it’s such a political issue.”
The study was supported in part by the department of laboratory medicine at the University of Washington, the department of pathology at the University of Iowa, and a grant from Abbott Diagnostics for in-kind high-sensitivity cardiac troponin I reagent. One coauthor reported financial relationships with Siemens Healthineers, Roche Diagnostics, Beckman Coulter, Becton, Dickinson, Abbott Diagnostics, Quidel Diagnostics, Sphingotech, and PixCell Medical. No other disclosures were reported.
A version of this article first appeared on Medscape.com.
Cardiac biomarkers vary according to sex hormones in healthy transgender adults, just as in cisgender individuals, a new cross-sectional study suggests.
Previous research in the general population has shown that females have a lower 99th percentile upper reference limit for high-sensitivity cardiac troponin (hs-cTn) than males, whereas N-terminal prohormone brain natriuretic peptide (NT-proBNP) concentrations are higher in females than males across all ages after puberty.
“That trend is similar for people that have been on gender-affirming hormones, saying that sex hormones are playing a role in how cardiac turnover happens in a healthy state,” study author Dina M. Greene, PhD, University of Washington, Seattle, said in an interview.
Although the number of transgender people seeking gender-affirming care is increasing, studies are limited and largely retrospective cohorts, she noted. The scientific literature evaluating and defining cardiac biomarker concentrations is “currently absent.”
The American Heart Association’s recent scientific statement on the cardiovascular health of transgender and gender diverse (TGD) people says mounting evidence points to worse CV health in TGD people and that part of this excess risk is driven by significant psychosocial stressors across the lifespan. “In addition, the use of gender-affirming hormone therapy may be associated with cardiometabolic changes, but health research in this area remains limited and, at times, contradictory.”
For the present study, Dr. Greene and colleagues reached out to LGBTQ-oriented primary care and internal medicine clinics in Seattle and Iowa City to recruit 79 transgender men prescribed testosterone (mean age, 28.8 years) and 93 transgender women (mean age, 35.1 years) prescribed estradiol for at least 12 months. The mean duration of hormone therapy was 4.8 and 3.5 years, respectively.
The median estradiol concentration was 51 pg/mL in transgender men and 207 pg/mL in transgender women. Median testosterone concentrations were 4.6 ng/mL and 0.4 ng/mL, respectively.
The cardiac biomarkers were measured with the ARCHITECT STAT (Abbott Diagnostics) and ACCESS (Beckman Coulter) high-sensitivity troponin I assays, the Elecsys Troponin T Gen 5 STAT assay (Roche Diagnostics), and the Elecsys ProBNP II immunoassay (Roche Diagnostics).
As reported in JAMA Cardiology, the median hs-cTnI level on the ARCHITECT STAT assay was 0.9 ng/L (range, 0.6-1.7) in transgender men and 0.6 ng/L (range, 0.3-1.0) in transgender women. The pattern was consistent across the two other assays.
In contrast, the median NT-proBNP level was 17 ng/L (range, 13-27) in transgender men and 49 ng/L (range, 32-86) in transgender women.
“It seems that sex hormone concentration is a stronger driver of baseline cardiac troponin and NT-proBNP concentrations relative to sex assigned at birth,” Dr. Greene said.
The observed differences in hs-cTn concentrations “are likely physiological and not pathological,” given that concentrations between healthy cisgender people are also apparent and not thought to portend adverse events, the authors noted.
Teasing out the clinical implications of sex-specific hs-cTn upper reference limits for ruling in acute myocardial infarction (MI), however, is complicated by biological and social factors that contribute to poorer outcomes in women, despite lower baseline levels, they added. “Ultimately, the psychosocial benefits of gender-affirming hormones are substantial, and informed consent is likely the ideal method to balance the undetermined risks.”
Dr. Greene pointed out that the study wasn’t powered to accurately calculate gender-specific hs-cTn 99th percentiles or reference intervals for NT-proBNP and assessed the biomarkers at a single time point.
For the transgender person presenting with chest pain, she said, the clinical implications are not yet known, but the data suggest that when sex-specific 99th percentiles for hs-cTn are used, the numeric value associated with the affirmed gender, rather than the sex assigned at birth, may be the appropriate URL.
“It really depends on what the triage pathway is and if that pathway has differences for people of different sexes and how often people get serial measurements,” Dr. Greene said. “Within this population, it’s very important to look at those serial measurements because for people that are not cismen, those 99th percentiles when they’re non–sex specific, are going to favor in detection of a heart attack. So, you need to look at the second value to make sure there hasn’t been a change over time.”
The observed differences in the distribution of NT-proBNP concentrations is similar to that in the cisgender population, Dr. Greene noted. But these differences do not lead to sex-specific diagnostic thresholds because of the significant elevations present in overt heart failure and cardiovascular disease. “For NT-proBNP, it’s not as important. People don’t usually have a little bit of heart failure, they have heart failure, where people have small MIs.”
Dr. Greene said she would like to see larger trials looking at biomarker measurements and cardiac imaging before hormone therapy but that the biggest issue is the need for inclusion of transgender people in all cardiovascular trials.
“The sample sizes are never going to be as big as we get for cisgender people for a number of reasons but ensuring that it’s something that’s being asked on intake and monitored over time so we can understand how transgender people fit into the general population for cardiac disease,” Dr. Greene said. “And so, we can normalize that they exist. I keep driving this point home, but this is the biggest thing right now when it’s such a political issue.”
The study was supported in part by the department of laboratory medicine at the University of Washington, the department of pathology at the University of Iowa, and a grant from Abbott Diagnostics for in-kind high-sensitivity cardiac troponin I reagent. One coauthor reported financial relationships with Siemens Healthineers, Roche Diagnostics, Beckman Coulter, Becton, Dickinson, Abbott Diagnostics, Quidel Diagnostics, Sphingotech, and PixCell Medical. No other disclosures were reported.
A version of this article first appeared on Medscape.com.
FROM JAMA CARDIOLOGY
Cre8 EVO stent loses sweet spot in diabetes at 2 years: SUGAR
BOSTON – Despite a promising start, extended follow-up from the SUGAR trial found that the Cre8 EVO drug-eluting stent could not maintain superiority over the Resolute Onyx DES at 2 years in patients with diabetes undergoing revascularization for coronary artery disease.
The Cre8 EVO stent (Alvimedica) is not available in the United States but, as previously reported, caused a stir last year after demonstrating a 35% relative risk reduction in the primary endpoint of target lesion failure (TLF) at 1 year in a prespecified superiority analysis.
At 2 years, however, the TLF rate was 10.4% with the polymer-free Cre8 EVO amphilimus-eluting stent and 12.1% with the durable polymer Resolute Onyx (Medtronic) zotarolimus-eluting stent, which did not achieve superiority (hazard ratio, 0.84; 95% confidence interval, 0.60-1.19).
Rates were numerically lower with the Cre8 EVO stent for the endpoint’s individual components of cardiac death (3.1% vs. 3.4%), target vessel MI (6.6% vs. 7.6%), and target lesion revascularization (4.3% vs. 4.6%).
Results were also similar between the Cre8 EVO and Resolute Onyx stents for all-cause mortality (7.1% vs. 6.8%), any MI (9.0% vs. 9.2%), target vessel revascularization (5.5% vs. 5.1%), all new revascularizations (7.6% vs. 9.4%), definite stent thrombosis (1.0% vs. 1.2%), and major adverse cardiac events (18.3% vs. 20.8%), Pablo Salinas, MD, PhD, of Hospital Clinico San Carlos, Madrid, reported at the Transcatheter Cardiovascular Therapeutics annual meeting.
He noted that all-cause mortality was 7% in just 2 years in the diabetic cohort, or twice the number of cardiac deaths. “In other words, these patients had the same chance of dying from cardiac causes and noncardiac causes, so we need a more comprehensive approach to the disease. Also, if you look at all new revascularizations, roughly 50% were off target, so there is disease progression at 2 years in this population.”
Among the 586 Cre8 EVO and 589 Resolute Onyx patients who underwent percutaneous coronary intervention (PCI), roughly half had multivessel coronary artery disease, 83% had hypertension, 81% had dyslipidemia, and 21% were current smokers. Nearly all patients had diabetes type 2 for an average of 10.6 years for Cre8 EVO and 11.4 years for Resolute Onyx, with hemoglobin A1c levels of 7.4% and 7.5%, respectively.
Although there is “insufficient evidence” the Cre8 EVO stent is superior to the Resolute Onyx stent with regard to TLF, Dr. Salinas concluded extended follow-up until 5 years is warranted.
During a discussion of the results, Dr. Salinas said he expects the 5-year results will “probably go parallel” but that it’s worth following this very valuable cohort. “There are not so many trials with 1,000 diabetic patients. We always speak about how complex they are, the results are bad, but we don’t use the diabetic population in trials,” he said at the meeting sponsored by the Cardiovascular Research Foundation.
Asked during a TCT press conference what could have caused the catch-up in TLF at 2 years, Dr. Salinas said there were only 25 primary events from years 1 to 2, driven primarily by periprocedural MI, but that the timing of restenosis was different. Events accrued “drop by drop” with the Cre8 EVO, whereas with the Resolute Onyx there was a “bump in restenosis” after 6 months “but then it is very nice to see it is flat, which means that durable polymers are also safe because we have not seen late events.”
Press conference discussant Carlo Di Mario, MD, from Careggi University Hospital, Florence, Italy, who was not involved in the study, said the reversal of superiority for the Cre8 EVO might be a “bitter note” for the investigators but “maybe it is not bitter for us because overall, the percentage of figures are so low that it’s very difficult to find a difference” between the two stents.
Roxana Mehran, MD, of Icahn School of Medicine at Mount Sinai, New York, who previously described the 1-year results as “almost too good to be true,” commented to this news organization, “We just saw in this trial, no benefit whatsoever at 2 years in terms of target lesion failure. So it’s very important for us to evaluate this going forward.”
She continued, “We’ve always been talking about these biodegradable polymers and then going back to the bare metal stent – oh that’s great because polymers aren’t so good – but now we’re seeing durable polymers may be okay, especially with the current technology.”
Asked whether Cre8 EVO, which is CE mark certified in Europe, remains an option in light of the new results, Dr. Mehran said, “I don’t think it kills it. It’s not worse; it’s another stent that’s available.”
Nevertheless, “what we’re looking for is some efficacious benefit for diabetic patients. We don’t have one yet,” observed Dr. Mehran, who is leading the ABILITY Diabetes Global trial, which just finished enrolling 3,000 patients with diabetes and is testing PCI with the Abluminus DES+ sirolimus-eluting stent system vs. the Xience everolimus-eluting stent. The study is estimated to be complete in August 2024.
The study was funded by the Spanish Society of Cardiology. Dr. Salinas reported consulting fees/honoraria from Boston Scientific, Abbott Vascular, Biomenco, and Medtronic.
A version of this article first appeared on Medscape.com.
BOSTON – Despite a promising start, extended follow-up from the SUGAR trial found that the Cre8 EVO drug-eluting stent could not maintain superiority over the Resolute Onyx DES at 2 years in patients with diabetes undergoing revascularization for coronary artery disease.
The Cre8 EVO stent (Alvimedica) is not available in the United States but, as previously reported, caused a stir last year after demonstrating a 35% relative risk reduction in the primary endpoint of target lesion failure (TLF) at 1 year in a prespecified superiority analysis.
At 2 years, however, the TLF rate was 10.4% with the polymer-free Cre8 EVO amphilimus-eluting stent and 12.1% with the durable polymer Resolute Onyx (Medtronic) zotarolimus-eluting stent, which did not achieve superiority (hazard ratio, 0.84; 95% confidence interval, 0.60-1.19).
Rates were numerically lower with the Cre8 EVO stent for the endpoint’s individual components of cardiac death (3.1% vs. 3.4%), target vessel MI (6.6% vs. 7.6%), and target lesion revascularization (4.3% vs. 4.6%).
Results were also similar between the Cre8 EVO and Resolute Onyx stents for all-cause mortality (7.1% vs. 6.8%), any MI (9.0% vs. 9.2%), target vessel revascularization (5.5% vs. 5.1%), all new revascularizations (7.6% vs. 9.4%), definite stent thrombosis (1.0% vs. 1.2%), and major adverse cardiac events (18.3% vs. 20.8%), Pablo Salinas, MD, PhD, of Hospital Clinico San Carlos, Madrid, reported at the Transcatheter Cardiovascular Therapeutics annual meeting.
He noted that all-cause mortality was 7% in just 2 years in the diabetic cohort, or twice the number of cardiac deaths. “In other words, these patients had the same chance of dying from cardiac causes and noncardiac causes, so we need a more comprehensive approach to the disease. Also, if you look at all new revascularizations, roughly 50% were off target, so there is disease progression at 2 years in this population.”
Among the 586 Cre8 EVO and 589 Resolute Onyx patients who underwent percutaneous coronary intervention (PCI), roughly half had multivessel coronary artery disease, 83% had hypertension, 81% had dyslipidemia, and 21% were current smokers. Nearly all patients had diabetes type 2 for an average of 10.6 years for Cre8 EVO and 11.4 years for Resolute Onyx, with hemoglobin A1c levels of 7.4% and 7.5%, respectively.
Although there is “insufficient evidence” the Cre8 EVO stent is superior to the Resolute Onyx stent with regard to TLF, Dr. Salinas concluded extended follow-up until 5 years is warranted.
During a discussion of the results, Dr. Salinas said he expects the 5-year results will “probably go parallel” but that it’s worth following this very valuable cohort. “There are not so many trials with 1,000 diabetic patients. We always speak about how complex they are, the results are bad, but we don’t use the diabetic population in trials,” he said at the meeting sponsored by the Cardiovascular Research Foundation.
Asked during a TCT press conference what could have caused the catch-up in TLF at 2 years, Dr. Salinas said there were only 25 primary events from years 1 to 2, driven primarily by periprocedural MI, but that the timing of restenosis was different. Events accrued “drop by drop” with the Cre8 EVO, whereas with the Resolute Onyx there was a “bump in restenosis” after 6 months “but then it is very nice to see it is flat, which means that durable polymers are also safe because we have not seen late events.”
Press conference discussant Carlo Di Mario, MD, from Careggi University Hospital, Florence, Italy, who was not involved in the study, said the reversal of superiority for the Cre8 EVO might be a “bitter note” for the investigators but “maybe it is not bitter for us because overall, the percentage of figures are so low that it’s very difficult to find a difference” between the two stents.
Roxana Mehran, MD, of Icahn School of Medicine at Mount Sinai, New York, who previously described the 1-year results as “almost too good to be true,” commented to this news organization, “We just saw in this trial, no benefit whatsoever at 2 years in terms of target lesion failure. So it’s very important for us to evaluate this going forward.”
She continued, “We’ve always been talking about these biodegradable polymers and then going back to the bare metal stent – oh that’s great because polymers aren’t so good – but now we’re seeing durable polymers may be okay, especially with the current technology.”
Asked whether Cre8 EVO, which is CE mark certified in Europe, remains an option in light of the new results, Dr. Mehran said, “I don’t think it kills it. It’s not worse; it’s another stent that’s available.”
Nevertheless, “what we’re looking for is some efficacious benefit for diabetic patients. We don’t have one yet,” observed Dr. Mehran, who is leading the ABILITY Diabetes Global trial, which just finished enrolling 3,000 patients with diabetes and is testing PCI with the Abluminus DES+ sirolimus-eluting stent system vs. the Xience everolimus-eluting stent. The study is estimated to be complete in August 2024.
The study was funded by the Spanish Society of Cardiology. Dr. Salinas reported consulting fees/honoraria from Boston Scientific, Abbott Vascular, Biomenco, and Medtronic.
A version of this article first appeared on Medscape.com.
BOSTON – Despite a promising start, extended follow-up from the SUGAR trial found that the Cre8 EVO drug-eluting stent could not maintain superiority over the Resolute Onyx DES at 2 years in patients with diabetes undergoing revascularization for coronary artery disease.
The Cre8 EVO stent (Alvimedica) is not available in the United States but, as previously reported, caused a stir last year after demonstrating a 35% relative risk reduction in the primary endpoint of target lesion failure (TLF) at 1 year in a prespecified superiority analysis.
At 2 years, however, the TLF rate was 10.4% with the polymer-free Cre8 EVO amphilimus-eluting stent and 12.1% with the durable polymer Resolute Onyx (Medtronic) zotarolimus-eluting stent, which did not achieve superiority (hazard ratio, 0.84; 95% confidence interval, 0.60-1.19).
Rates were numerically lower with the Cre8 EVO stent for the endpoint’s individual components of cardiac death (3.1% vs. 3.4%), target vessel MI (6.6% vs. 7.6%), and target lesion revascularization (4.3% vs. 4.6%).
Results were also similar between the Cre8 EVO and Resolute Onyx stents for all-cause mortality (7.1% vs. 6.8%), any MI (9.0% vs. 9.2%), target vessel revascularization (5.5% vs. 5.1%), all new revascularizations (7.6% vs. 9.4%), definite stent thrombosis (1.0% vs. 1.2%), and major adverse cardiac events (18.3% vs. 20.8%), Pablo Salinas, MD, PhD, of Hospital Clinico San Carlos, Madrid, reported at the Transcatheter Cardiovascular Therapeutics annual meeting.
He noted that all-cause mortality was 7% in just 2 years in the diabetic cohort, or twice the number of cardiac deaths. “In other words, these patients had the same chance of dying from cardiac causes and noncardiac causes, so we need a more comprehensive approach to the disease. Also, if you look at all new revascularizations, roughly 50% were off target, so there is disease progression at 2 years in this population.”
Among the 586 Cre8 EVO and 589 Resolute Onyx patients who underwent percutaneous coronary intervention (PCI), roughly half had multivessel coronary artery disease, 83% had hypertension, 81% had dyslipidemia, and 21% were current smokers. Nearly all patients had diabetes type 2 for an average of 10.6 years for Cre8 EVO and 11.4 years for Resolute Onyx, with hemoglobin A1c levels of 7.4% and 7.5%, respectively.
Although there is “insufficient evidence” the Cre8 EVO stent is superior to the Resolute Onyx stent with regard to TLF, Dr. Salinas concluded extended follow-up until 5 years is warranted.
During a discussion of the results, Dr. Salinas said he expects the 5-year results will “probably go parallel” but that it’s worth following this very valuable cohort. “There are not so many trials with 1,000 diabetic patients. We always speak about how complex they are, the results are bad, but we don’t use the diabetic population in trials,” he said at the meeting sponsored by the Cardiovascular Research Foundation.
Asked during a TCT press conference what could have caused the catch-up in TLF at 2 years, Dr. Salinas said there were only 25 primary events from years 1 to 2, driven primarily by periprocedural MI, but that the timing of restenosis was different. Events accrued “drop by drop” with the Cre8 EVO, whereas with the Resolute Onyx there was a “bump in restenosis” after 6 months “but then it is very nice to see it is flat, which means that durable polymers are also safe because we have not seen late events.”
Press conference discussant Carlo Di Mario, MD, from Careggi University Hospital, Florence, Italy, who was not involved in the study, said the reversal of superiority for the Cre8 EVO might be a “bitter note” for the investigators but “maybe it is not bitter for us because overall, the percentage of figures are so low that it’s very difficult to find a difference” between the two stents.
Roxana Mehran, MD, of Icahn School of Medicine at Mount Sinai, New York, who previously described the 1-year results as “almost too good to be true,” commented to this news organization, “We just saw in this trial, no benefit whatsoever at 2 years in terms of target lesion failure. So it’s very important for us to evaluate this going forward.”
She continued, “We’ve always been talking about these biodegradable polymers and then going back to the bare metal stent – oh that’s great because polymers aren’t so good – but now we’re seeing durable polymers may be okay, especially with the current technology.”
Asked whether Cre8 EVO, which is CE mark certified in Europe, remains an option in light of the new results, Dr. Mehran said, “I don’t think it kills it. It’s not worse; it’s another stent that’s available.”
Nevertheless, “what we’re looking for is some efficacious benefit for diabetic patients. We don’t have one yet,” observed Dr. Mehran, who is leading the ABILITY Diabetes Global trial, which just finished enrolling 3,000 patients with diabetes and is testing PCI with the Abluminus DES+ sirolimus-eluting stent system vs. the Xience everolimus-eluting stent. The study is estimated to be complete in August 2024.
The study was funded by the Spanish Society of Cardiology. Dr. Salinas reported consulting fees/honoraria from Boston Scientific, Abbott Vascular, Biomenco, and Medtronic.
A version of this article first appeared on Medscape.com.
AT TCT 2022
Amulet, Watchman 2.5 LAAO outcomes neck and neck at 3 years
The Amplatzer Amulet (Abbott) and first-generation Watchman 2.5 (Boston Scientific) devices provide relatively comparable results out to 3 years after left atrial appendage occlusion (LAAO), longer follow-up from the Amplatzer Amulet Left Atrial Appendage Occluder Versus Watchman Device for Stroke Prophylaxis (Amulet IDE) trial shows.
“The dual-seal Amplatzer Amulet left atrial appendage occluder continued to demonstrate safety and effectiveness through 3 years,” principal investigator Dhanunjaya Lakkireddy, MD, said in a late-breaking session at the recent Transcatheter Cardiovascular Therapeutics annual meeting.
Preliminary results, reported last year, showed that procedural complications were higher with the Amplatzer but that it provided superior closure of the left atrial appendage (LAA) at 45 days and was noninferior with respect to safety at 12 months and efficacy at 18 months.
Amulet IDE is the largest head-to-head comparison of the two devices, enrolling 1,878 high-risk patients with nonvalvular atrial fibrillation undergoing LAA closure to reduce the risk of stroke.
Three-year follow-up was higher with the Amulet device than with the Watchman, at 721 vs. 659 patients, driven by increased deaths (85 vs. 63) and withdrawals (50 vs. 23) in the Watchman group within 18 months, noted Dr. Lakkireddy, Kansas City Heart Rhythm Institute and Research Foundation, Overland Park, Kan.
Use of oral anticoagulation was higher in the Watchman group at 6 months (2.8% vs. 4.7%; P = .04), 18 months (3.1% vs. 5.6%; P = .01), and 3 years (3.7% vs. 7.3%; P < .01).
This was primarily driven by more late device-related thrombus (DRT) after 6 months with the Watchman device than with the Amulet occluder (23 vs. 10). “Perhaps the dual-closure mechanism of the Amulet explains this fundamental difference, where you have a nice smooth disc that covers the ostium,” he posited.
At 3 years, rates of cardiovascular death trended lower with Amulet than with Watchman (6.6% vs. 8.5%; P = .14), as did all-cause deaths (14.6% vs. 17.9%; P = .07).
Most cardiovascular deaths in the Amulet group were not preceded by a device factor, whereas DRT (1 vs. 4) and peridevice leak 3 mm or more (5 vs. 15) frequently preceded these deaths in the Watchman group, Dr. Lakkireddy observed. No pericardial effusion-related deaths occurred in either group.
Major bleeding, however, trended higher for the Amulet, at 16.1%, compared with 14.7% for the Watchman (P = .46). Ischemic stroke and systemic embolic rates also trended higher for Amulet, at 5%, and 4.6% for Watchman.
The protocol recommended aspirin only for both groups after 6 months. None of the 29 Amulet and 3 of the 29 Watchman patients with an ischemic stroke were on oral anticoagulation at the time of the stroke.
Device factors, however, frequently preceded ischemic strokes in the Watchman group, Dr. Lakkireddy said. DRT occurred in 1 patient with Amulet and 2 patients with Watchman and peridevice leak in 3 with Amulet and 15 with Watchman. “Again, the peridevice leak issue really stands out as an important factor,” he said at the meeting, which was sponsored by the Cardiovascular Research Foundation.
Based on “data from the large trials, it’s clearly evident that the presence of peridevice leak significantly raises the risk of stroke in follow-up,” he said. “So, attention has to be paid to the choice of the device and how we can mitigate the risk of peridevice leaks in these patients.”
The composite of stroke, systemic embolism, and cardiovascular death occurred in 11.1% of patients with Amulet and 12.7% with Watchman (P = .31).
Asked following the formal presentation whether the results justify use of one device over the other for LAA occlusion, Dr. Lakkireddy said he likes the dual closure mechanism of the Amulet and is more likely to use it in patients with proximal lobes, very large appendages, or a relatively shallow appendage. “In the rest of the cases, I think it’s a toss-up.”
As for how generalizable the results are, he noted that the study tested the Amulet against the legacy Watchman 2.5 but that the second-generation Watchman FLX is available in a larger size and has shown improved performance.
The Amplatzer Amulet does not require oral anticoagulants at discharge. However, the indication for the Watchman FLX was recently expanded to include 45-day dual antiplatelet therapy as a postprocedure alternative to oral anticoagulation plus aspirin.
Going forward, the “next evolution” is to test the Watchman FLX and Amulet on either single antiplatelet or a dual antiplatelet regimen without oral anticoagulation, he suggested.
Results from SWISS APERO, the first randomized trial to compare the Amulet and Watchman FLX (and a handful of 2.5 devices) in 221 patients, showed that the devices are not interchangeable for rates of complications or leaks.
During a press conference prior to the presentation, discussant Federico Asch, MD, MedStar Health Research Institute, Washington, said, “the most exciting thing here is that we have good options. We now can start to tease out which patients will benefit best from one or the other because we actually have two options.”
The Amulet IDE trial was funded by Abbott. Dr. Lakkireddy reports that he or his spouse/partner have received grant/research support from Abbott, AtriCure, Alta Thera, Medtronic, Biosense Webster, Biotronik, and Boston Scientific; and speaker honoraria from Abbott, Medtronic, Biotronik, and Boston Scientific.
A version of this article first appeared on Medscape.com.
The Amplatzer Amulet (Abbott) and first-generation Watchman 2.5 (Boston Scientific) devices provide relatively comparable results out to 3 years after left atrial appendage occlusion (LAAO), longer follow-up from the Amplatzer Amulet Left Atrial Appendage Occluder Versus Watchman Device for Stroke Prophylaxis (Amulet IDE) trial shows.
“The dual-seal Amplatzer Amulet left atrial appendage occluder continued to demonstrate safety and effectiveness through 3 years,” principal investigator Dhanunjaya Lakkireddy, MD, said in a late-breaking session at the recent Transcatheter Cardiovascular Therapeutics annual meeting.
Preliminary results, reported last year, showed that procedural complications were higher with the Amplatzer but that it provided superior closure of the left atrial appendage (LAA) at 45 days and was noninferior with respect to safety at 12 months and efficacy at 18 months.
Amulet IDE is the largest head-to-head comparison of the two devices, enrolling 1,878 high-risk patients with nonvalvular atrial fibrillation undergoing LAA closure to reduce the risk of stroke.
Three-year follow-up was higher with the Amulet device than with the Watchman, at 721 vs. 659 patients, driven by increased deaths (85 vs. 63) and withdrawals (50 vs. 23) in the Watchman group within 18 months, noted Dr. Lakkireddy, Kansas City Heart Rhythm Institute and Research Foundation, Overland Park, Kan.
Use of oral anticoagulation was higher in the Watchman group at 6 months (2.8% vs. 4.7%; P = .04), 18 months (3.1% vs. 5.6%; P = .01), and 3 years (3.7% vs. 7.3%; P < .01).
This was primarily driven by more late device-related thrombus (DRT) after 6 months with the Watchman device than with the Amulet occluder (23 vs. 10). “Perhaps the dual-closure mechanism of the Amulet explains this fundamental difference, where you have a nice smooth disc that covers the ostium,” he posited.
At 3 years, rates of cardiovascular death trended lower with Amulet than with Watchman (6.6% vs. 8.5%; P = .14), as did all-cause deaths (14.6% vs. 17.9%; P = .07).
Most cardiovascular deaths in the Amulet group were not preceded by a device factor, whereas DRT (1 vs. 4) and peridevice leak 3 mm or more (5 vs. 15) frequently preceded these deaths in the Watchman group, Dr. Lakkireddy observed. No pericardial effusion-related deaths occurred in either group.
Major bleeding, however, trended higher for the Amulet, at 16.1%, compared with 14.7% for the Watchman (P = .46). Ischemic stroke and systemic embolic rates also trended higher for Amulet, at 5%, and 4.6% for Watchman.
The protocol recommended aspirin only for both groups after 6 months. None of the 29 Amulet and 3 of the 29 Watchman patients with an ischemic stroke were on oral anticoagulation at the time of the stroke.
Device factors, however, frequently preceded ischemic strokes in the Watchman group, Dr. Lakkireddy said. DRT occurred in 1 patient with Amulet and 2 patients with Watchman and peridevice leak in 3 with Amulet and 15 with Watchman. “Again, the peridevice leak issue really stands out as an important factor,” he said at the meeting, which was sponsored by the Cardiovascular Research Foundation.
Based on “data from the large trials, it’s clearly evident that the presence of peridevice leak significantly raises the risk of stroke in follow-up,” he said. “So, attention has to be paid to the choice of the device and how we can mitigate the risk of peridevice leaks in these patients.”
The composite of stroke, systemic embolism, and cardiovascular death occurred in 11.1% of patients with Amulet and 12.7% with Watchman (P = .31).
Asked following the formal presentation whether the results justify use of one device over the other for LAA occlusion, Dr. Lakkireddy said he likes the dual closure mechanism of the Amulet and is more likely to use it in patients with proximal lobes, very large appendages, or a relatively shallow appendage. “In the rest of the cases, I think it’s a toss-up.”
As for how generalizable the results are, he noted that the study tested the Amulet against the legacy Watchman 2.5 but that the second-generation Watchman FLX is available in a larger size and has shown improved performance.
The Amplatzer Amulet does not require oral anticoagulants at discharge. However, the indication for the Watchman FLX was recently expanded to include 45-day dual antiplatelet therapy as a postprocedure alternative to oral anticoagulation plus aspirin.
Going forward, the “next evolution” is to test the Watchman FLX and Amulet on either single antiplatelet or a dual antiplatelet regimen without oral anticoagulation, he suggested.
Results from SWISS APERO, the first randomized trial to compare the Amulet and Watchman FLX (and a handful of 2.5 devices) in 221 patients, showed that the devices are not interchangeable for rates of complications or leaks.
During a press conference prior to the presentation, discussant Federico Asch, MD, MedStar Health Research Institute, Washington, said, “the most exciting thing here is that we have good options. We now can start to tease out which patients will benefit best from one or the other because we actually have two options.”
The Amulet IDE trial was funded by Abbott. Dr. Lakkireddy reports that he or his spouse/partner have received grant/research support from Abbott, AtriCure, Alta Thera, Medtronic, Biosense Webster, Biotronik, and Boston Scientific; and speaker honoraria from Abbott, Medtronic, Biotronik, and Boston Scientific.
A version of this article first appeared on Medscape.com.
The Amplatzer Amulet (Abbott) and first-generation Watchman 2.5 (Boston Scientific) devices provide relatively comparable results out to 3 years after left atrial appendage occlusion (LAAO), longer follow-up from the Amplatzer Amulet Left Atrial Appendage Occluder Versus Watchman Device for Stroke Prophylaxis (Amulet IDE) trial shows.
“The dual-seal Amplatzer Amulet left atrial appendage occluder continued to demonstrate safety and effectiveness through 3 years,” principal investigator Dhanunjaya Lakkireddy, MD, said in a late-breaking session at the recent Transcatheter Cardiovascular Therapeutics annual meeting.
Preliminary results, reported last year, showed that procedural complications were higher with the Amplatzer but that it provided superior closure of the left atrial appendage (LAA) at 45 days and was noninferior with respect to safety at 12 months and efficacy at 18 months.
Amulet IDE is the largest head-to-head comparison of the two devices, enrolling 1,878 high-risk patients with nonvalvular atrial fibrillation undergoing LAA closure to reduce the risk of stroke.
Three-year follow-up was higher with the Amulet device than with the Watchman, at 721 vs. 659 patients, driven by increased deaths (85 vs. 63) and withdrawals (50 vs. 23) in the Watchman group within 18 months, noted Dr. Lakkireddy, Kansas City Heart Rhythm Institute and Research Foundation, Overland Park, Kan.
Use of oral anticoagulation was higher in the Watchman group at 6 months (2.8% vs. 4.7%; P = .04), 18 months (3.1% vs. 5.6%; P = .01), and 3 years (3.7% vs. 7.3%; P < .01).
This was primarily driven by more late device-related thrombus (DRT) after 6 months with the Watchman device than with the Amulet occluder (23 vs. 10). “Perhaps the dual-closure mechanism of the Amulet explains this fundamental difference, where you have a nice smooth disc that covers the ostium,” he posited.
At 3 years, rates of cardiovascular death trended lower with Amulet than with Watchman (6.6% vs. 8.5%; P = .14), as did all-cause deaths (14.6% vs. 17.9%; P = .07).
Most cardiovascular deaths in the Amulet group were not preceded by a device factor, whereas DRT (1 vs. 4) and peridevice leak 3 mm or more (5 vs. 15) frequently preceded these deaths in the Watchman group, Dr. Lakkireddy observed. No pericardial effusion-related deaths occurred in either group.
Major bleeding, however, trended higher for the Amulet, at 16.1%, compared with 14.7% for the Watchman (P = .46). Ischemic stroke and systemic embolic rates also trended higher for Amulet, at 5%, and 4.6% for Watchman.
The protocol recommended aspirin only for both groups after 6 months. None of the 29 Amulet and 3 of the 29 Watchman patients with an ischemic stroke were on oral anticoagulation at the time of the stroke.
Device factors, however, frequently preceded ischemic strokes in the Watchman group, Dr. Lakkireddy said. DRT occurred in 1 patient with Amulet and 2 patients with Watchman and peridevice leak in 3 with Amulet and 15 with Watchman. “Again, the peridevice leak issue really stands out as an important factor,” he said at the meeting, which was sponsored by the Cardiovascular Research Foundation.
Based on “data from the large trials, it’s clearly evident that the presence of peridevice leak significantly raises the risk of stroke in follow-up,” he said. “So, attention has to be paid to the choice of the device and how we can mitigate the risk of peridevice leaks in these patients.”
The composite of stroke, systemic embolism, and cardiovascular death occurred in 11.1% of patients with Amulet and 12.7% with Watchman (P = .31).
Asked following the formal presentation whether the results justify use of one device over the other for LAA occlusion, Dr. Lakkireddy said he likes the dual closure mechanism of the Amulet and is more likely to use it in patients with proximal lobes, very large appendages, or a relatively shallow appendage. “In the rest of the cases, I think it’s a toss-up.”
As for how generalizable the results are, he noted that the study tested the Amulet against the legacy Watchman 2.5 but that the second-generation Watchman FLX is available in a larger size and has shown improved performance.
The Amplatzer Amulet does not require oral anticoagulants at discharge. However, the indication for the Watchman FLX was recently expanded to include 45-day dual antiplatelet therapy as a postprocedure alternative to oral anticoagulation plus aspirin.
Going forward, the “next evolution” is to test the Watchman FLX and Amulet on either single antiplatelet or a dual antiplatelet regimen without oral anticoagulation, he suggested.
Results from SWISS APERO, the first randomized trial to compare the Amulet and Watchman FLX (and a handful of 2.5 devices) in 221 patients, showed that the devices are not interchangeable for rates of complications or leaks.
During a press conference prior to the presentation, discussant Federico Asch, MD, MedStar Health Research Institute, Washington, said, “the most exciting thing here is that we have good options. We now can start to tease out which patients will benefit best from one or the other because we actually have two options.”
The Amulet IDE trial was funded by Abbott. Dr. Lakkireddy reports that he or his spouse/partner have received grant/research support from Abbott, AtriCure, Alta Thera, Medtronic, Biosense Webster, Biotronik, and Boston Scientific; and speaker honoraria from Abbott, Medtronic, Biotronik, and Boston Scientific.
A version of this article first appeared on Medscape.com.
FROM TCT 2022
Autoimmune diseases linked to spike in post-MI events
, in a large propensity-matched analysis.
At a median of 2 years after their MI, Medicare beneficiaries with an IMID had adjusted risks that were:
- 15% higher for all-cause death (hazard ratio, 1.15);
- 12% higher for heart failure (HR, 1.12);
- 8% higher for recurrent MI (HR, 1.08); and
- 6% higher risk for coronary reintervention (HR, 1.06; P < .05 for all).
In addition, interventions known to improve outcomes in this context, such as coronary revascularization, were less common in patients with IMID.
“This could be because they usually are sicker and have more risk factors when they present, like kidney disease, so maybe they’re not eligible for the therapy. But by itself, it was surprising they’re not offered these interventions as common[ly] as people who don’t have the disease,” Amgad Mentias, MD, a clinical cardiologist at the Cleveland Clinic, said in an interview.
The study was published Sept. 14 in the Journal of the American Heart Association, with Dr. Mentias as senior author and Heba Wassif, MD, MPH, also with Cleveland Clinic, as first author.
IMIDs, such as rheumatoid arthritis, psoriasis, lupus, and inflammatory bowel disease, are known to be associated with significantly higher cardiovascular disease (CVD) risk due to a greater prevalence of traditional CVD risk factors and chronic systemic inflammation.
Certain disease-modifying agents may also increase patients’ cardiovascular risk. This has been a long-simmering issue for the arthritis and ulcerative colitis drug tofacitinib (Xeljanz, Xeljanz XR), resulting in an updated boxed warning in 2021.
Many of these patients also have joint disease, pain, and fatigue, which can limit physical activity, Dr. Mentias said. “So these small nuances of how to manage these patients, or balance between controlling the inflammation but also improv[ing] cardiac risk factors, is not an easy task.”
Evidence regarding post-MI events has been inconsistent and limited to smaller single-center studies, he said. After propensity-score matching, the present study included 59,820 patients with and 178,547 patients without rheumatic IMIDs followed for a maximum of 6 years.
They were drawn from a cohort of 1.6 million persons aged 65 or older in the Medicare Provider Analysis and Review (MedPAR) file who had been admitted for an MI between 2014 and 2019. Of these, 60,072 had a prior history of rheumatic IMIDs, most commonly rheumatoid arthritis (77.8%), followed by systemic lupus erythematosus (12.2%), psoriasis (5.1%), systemic sclerosis (2.8%), and myositis/dermatomyositis (1.8%).
Patients with an IMID were more often women; had a higher prevalence of valve disease, pulmonary hypertension, hypothyroidism, and anemia; and were more likely to present with non–ST-segment MI (NSTEMI).
Rates of coronary angiography (46.1% vs. 51.5%), percutaneous coronary intervention (31.6% vs. 33.6%), and coronary artery bypass grafting (7.7% vs. 10.7%) were significantly lower in patients with IMIDs who had NSTEMI, compared with patients without an IMID who had NSTEMI. Rates of these interventions were also lower in patients with IMIDs who presented with STEMI versus their peers without an IMID, at 78.2% vs. 80.7%, 70.2% vs. 71.5%, and 4.9% vs. 6.4%, respectively.
Dr. Mentias pointed out that the emerging subspecialty of cardiorheumatology is gaining traction, especially at large hospitals and academic centers, but that less than one-third of persons in the United States with an IMID are likely to be under the care of such specialists.
“It’s important before developing an MI to try and control the different risk factors and improve the risk profile for these patients as much as possible by both specialties, and then, after an unfortunate event like MI happens, it’s important to make sure we offer therapies and treatments that are known to improve outcomes,” he said.
Commenting for this article, Jon Tyler Giles, MD, a clinical researcher who focuses on cardiovascular diseases in rheumatology at Columbia University Vagelos College of Physicians and Surgeons, New York, said that “at least for rheumatoid arthritis, this is something that we already knew. People with rheumatic arthritis, when they have a heart attack, are less likely to get the standard kind of treatments and have worse outcomes. This is a little larger sample, but it’s not a surprise, not a surprise at all.”
He noted that the study could have answered questions regarding potential drivers, but “they didn’t dig down into any of the factors that were associated with the poorer outcomes in the patients with rheumatoid arthritis and lupus and scleroderma.”
Indeed, the investigators acknowledge that the study lacked information on coronary anatomy, duration and severity of the autoimmune disease, imaging data, and medications such as anti-inflammatory or immune-targeted therapies.
Dr. Giles highlighted several factors that can contribute to a poorer post-MI prognosis in patients with rheumatic diseases; these include frailty, being more hypercoaguable, increased rates of myocardial dysfunction and other heart and blood vessel diseases, and chronic treatment with steroids and nonsteroidal anti-inflammatory drugs that often interferes with anticoagulation after a MI or when putting in a stent. “So, there’s lot of moving parts, and not one single thing that is likely the answer.”
In addition, he said, “there’s always going to be a portion of these patients who, despite doing the best that we can with treatment, are going to have very severe disease. That may or may not be the subset of patients that did the worst, but likely they’re overrepresented in those patients.”
Finally, the inability to move the needle may lie with the lack of evidence-based screening and management guidelines for cardiovascular disease in any rheumatic disease, Dr. Giles observed. “There’s no guideline for us to use to decide who needs screening over and above what’s recommended for the general population, and then, even if you do screen, what do you do other than what you would normally?”
Rheumatologists are often reluctant to take up the cardiovascular screening side of things because visits are short, and a lot of that time is spent trying to manage the inflammatory components of a patient’s disease, he said. There’s also a barrier in getting some patients to add a cardiologist to the mix of physicians they already see, especially if they don’t have any symptoms.
“If someone has had an event, it’s a lot easier for people to be convinced to go see the cardiologist, obviously, but prior to having an event, the preventative side of things is something that often gets missed or goes to the wayside,” Dr. Giles said.
The study was partly funded by philanthropic gifts by the Haslam family, Bailey family, and Khouri family to the Cleveland Clinic for coauthor Dr. Milind Desai’s research. Dr. Desai is a consultant for Medtronic and Bristol Myers Squibb and serves on an executive steering committee of a BMS-sponsored trial. The remaining authors report having no relevant disclosures. Dr. Giles is a consultant on drug cardiovascular safety for Pfizer, AbbVie, and Eli Lilly.
A version of this article first appeared on Medscape.com.
, in a large propensity-matched analysis.
At a median of 2 years after their MI, Medicare beneficiaries with an IMID had adjusted risks that were:
- 15% higher for all-cause death (hazard ratio, 1.15);
- 12% higher for heart failure (HR, 1.12);
- 8% higher for recurrent MI (HR, 1.08); and
- 6% higher risk for coronary reintervention (HR, 1.06; P < .05 for all).
In addition, interventions known to improve outcomes in this context, such as coronary revascularization, were less common in patients with IMID.
“This could be because they usually are sicker and have more risk factors when they present, like kidney disease, so maybe they’re not eligible for the therapy. But by itself, it was surprising they’re not offered these interventions as common[ly] as people who don’t have the disease,” Amgad Mentias, MD, a clinical cardiologist at the Cleveland Clinic, said in an interview.
The study was published Sept. 14 in the Journal of the American Heart Association, with Dr. Mentias as senior author and Heba Wassif, MD, MPH, also with Cleveland Clinic, as first author.
IMIDs, such as rheumatoid arthritis, psoriasis, lupus, and inflammatory bowel disease, are known to be associated with significantly higher cardiovascular disease (CVD) risk due to a greater prevalence of traditional CVD risk factors and chronic systemic inflammation.
Certain disease-modifying agents may also increase patients’ cardiovascular risk. This has been a long-simmering issue for the arthritis and ulcerative colitis drug tofacitinib (Xeljanz, Xeljanz XR), resulting in an updated boxed warning in 2021.
Many of these patients also have joint disease, pain, and fatigue, which can limit physical activity, Dr. Mentias said. “So these small nuances of how to manage these patients, or balance between controlling the inflammation but also improv[ing] cardiac risk factors, is not an easy task.”
Evidence regarding post-MI events has been inconsistent and limited to smaller single-center studies, he said. After propensity-score matching, the present study included 59,820 patients with and 178,547 patients without rheumatic IMIDs followed for a maximum of 6 years.
They were drawn from a cohort of 1.6 million persons aged 65 or older in the Medicare Provider Analysis and Review (MedPAR) file who had been admitted for an MI between 2014 and 2019. Of these, 60,072 had a prior history of rheumatic IMIDs, most commonly rheumatoid arthritis (77.8%), followed by systemic lupus erythematosus (12.2%), psoriasis (5.1%), systemic sclerosis (2.8%), and myositis/dermatomyositis (1.8%).
Patients with an IMID were more often women; had a higher prevalence of valve disease, pulmonary hypertension, hypothyroidism, and anemia; and were more likely to present with non–ST-segment MI (NSTEMI).
Rates of coronary angiography (46.1% vs. 51.5%), percutaneous coronary intervention (31.6% vs. 33.6%), and coronary artery bypass grafting (7.7% vs. 10.7%) were significantly lower in patients with IMIDs who had NSTEMI, compared with patients without an IMID who had NSTEMI. Rates of these interventions were also lower in patients with IMIDs who presented with STEMI versus their peers without an IMID, at 78.2% vs. 80.7%, 70.2% vs. 71.5%, and 4.9% vs. 6.4%, respectively.
Dr. Mentias pointed out that the emerging subspecialty of cardiorheumatology is gaining traction, especially at large hospitals and academic centers, but that less than one-third of persons in the United States with an IMID are likely to be under the care of such specialists.
“It’s important before developing an MI to try and control the different risk factors and improve the risk profile for these patients as much as possible by both specialties, and then, after an unfortunate event like MI happens, it’s important to make sure we offer therapies and treatments that are known to improve outcomes,” he said.
Commenting for this article, Jon Tyler Giles, MD, a clinical researcher who focuses on cardiovascular diseases in rheumatology at Columbia University Vagelos College of Physicians and Surgeons, New York, said that “at least for rheumatoid arthritis, this is something that we already knew. People with rheumatic arthritis, when they have a heart attack, are less likely to get the standard kind of treatments and have worse outcomes. This is a little larger sample, but it’s not a surprise, not a surprise at all.”
He noted that the study could have answered questions regarding potential drivers, but “they didn’t dig down into any of the factors that were associated with the poorer outcomes in the patients with rheumatoid arthritis and lupus and scleroderma.”
Indeed, the investigators acknowledge that the study lacked information on coronary anatomy, duration and severity of the autoimmune disease, imaging data, and medications such as anti-inflammatory or immune-targeted therapies.
Dr. Giles highlighted several factors that can contribute to a poorer post-MI prognosis in patients with rheumatic diseases; these include frailty, being more hypercoaguable, increased rates of myocardial dysfunction and other heart and blood vessel diseases, and chronic treatment with steroids and nonsteroidal anti-inflammatory drugs that often interferes with anticoagulation after a MI or when putting in a stent. “So, there’s lot of moving parts, and not one single thing that is likely the answer.”
In addition, he said, “there’s always going to be a portion of these patients who, despite doing the best that we can with treatment, are going to have very severe disease. That may or may not be the subset of patients that did the worst, but likely they’re overrepresented in those patients.”
Finally, the inability to move the needle may lie with the lack of evidence-based screening and management guidelines for cardiovascular disease in any rheumatic disease, Dr. Giles observed. “There’s no guideline for us to use to decide who needs screening over and above what’s recommended for the general population, and then, even if you do screen, what do you do other than what you would normally?”
Rheumatologists are often reluctant to take up the cardiovascular screening side of things because visits are short, and a lot of that time is spent trying to manage the inflammatory components of a patient’s disease, he said. There’s also a barrier in getting some patients to add a cardiologist to the mix of physicians they already see, especially if they don’t have any symptoms.
“If someone has had an event, it’s a lot easier for people to be convinced to go see the cardiologist, obviously, but prior to having an event, the preventative side of things is something that often gets missed or goes to the wayside,” Dr. Giles said.
The study was partly funded by philanthropic gifts by the Haslam family, Bailey family, and Khouri family to the Cleveland Clinic for coauthor Dr. Milind Desai’s research. Dr. Desai is a consultant for Medtronic and Bristol Myers Squibb and serves on an executive steering committee of a BMS-sponsored trial. The remaining authors report having no relevant disclosures. Dr. Giles is a consultant on drug cardiovascular safety for Pfizer, AbbVie, and Eli Lilly.
A version of this article first appeared on Medscape.com.
, in a large propensity-matched analysis.
At a median of 2 years after their MI, Medicare beneficiaries with an IMID had adjusted risks that were:
- 15% higher for all-cause death (hazard ratio, 1.15);
- 12% higher for heart failure (HR, 1.12);
- 8% higher for recurrent MI (HR, 1.08); and
- 6% higher risk for coronary reintervention (HR, 1.06; P < .05 for all).
In addition, interventions known to improve outcomes in this context, such as coronary revascularization, were less common in patients with IMID.
“This could be because they usually are sicker and have more risk factors when they present, like kidney disease, so maybe they’re not eligible for the therapy. But by itself, it was surprising they’re not offered these interventions as common[ly] as people who don’t have the disease,” Amgad Mentias, MD, a clinical cardiologist at the Cleveland Clinic, said in an interview.
The study was published Sept. 14 in the Journal of the American Heart Association, with Dr. Mentias as senior author and Heba Wassif, MD, MPH, also with Cleveland Clinic, as first author.
IMIDs, such as rheumatoid arthritis, psoriasis, lupus, and inflammatory bowel disease, are known to be associated with significantly higher cardiovascular disease (CVD) risk due to a greater prevalence of traditional CVD risk factors and chronic systemic inflammation.
Certain disease-modifying agents may also increase patients’ cardiovascular risk. This has been a long-simmering issue for the arthritis and ulcerative colitis drug tofacitinib (Xeljanz, Xeljanz XR), resulting in an updated boxed warning in 2021.
Many of these patients also have joint disease, pain, and fatigue, which can limit physical activity, Dr. Mentias said. “So these small nuances of how to manage these patients, or balance between controlling the inflammation but also improv[ing] cardiac risk factors, is not an easy task.”
Evidence regarding post-MI events has been inconsistent and limited to smaller single-center studies, he said. After propensity-score matching, the present study included 59,820 patients with and 178,547 patients without rheumatic IMIDs followed for a maximum of 6 years.
They were drawn from a cohort of 1.6 million persons aged 65 or older in the Medicare Provider Analysis and Review (MedPAR) file who had been admitted for an MI between 2014 and 2019. Of these, 60,072 had a prior history of rheumatic IMIDs, most commonly rheumatoid arthritis (77.8%), followed by systemic lupus erythematosus (12.2%), psoriasis (5.1%), systemic sclerosis (2.8%), and myositis/dermatomyositis (1.8%).
Patients with an IMID were more often women; had a higher prevalence of valve disease, pulmonary hypertension, hypothyroidism, and anemia; and were more likely to present with non–ST-segment MI (NSTEMI).
Rates of coronary angiography (46.1% vs. 51.5%), percutaneous coronary intervention (31.6% vs. 33.6%), and coronary artery bypass grafting (7.7% vs. 10.7%) were significantly lower in patients with IMIDs who had NSTEMI, compared with patients without an IMID who had NSTEMI. Rates of these interventions were also lower in patients with IMIDs who presented with STEMI versus their peers without an IMID, at 78.2% vs. 80.7%, 70.2% vs. 71.5%, and 4.9% vs. 6.4%, respectively.
Dr. Mentias pointed out that the emerging subspecialty of cardiorheumatology is gaining traction, especially at large hospitals and academic centers, but that less than one-third of persons in the United States with an IMID are likely to be under the care of such specialists.
“It’s important before developing an MI to try and control the different risk factors and improve the risk profile for these patients as much as possible by both specialties, and then, after an unfortunate event like MI happens, it’s important to make sure we offer therapies and treatments that are known to improve outcomes,” he said.
Commenting for this article, Jon Tyler Giles, MD, a clinical researcher who focuses on cardiovascular diseases in rheumatology at Columbia University Vagelos College of Physicians and Surgeons, New York, said that “at least for rheumatoid arthritis, this is something that we already knew. People with rheumatic arthritis, when they have a heart attack, are less likely to get the standard kind of treatments and have worse outcomes. This is a little larger sample, but it’s not a surprise, not a surprise at all.”
He noted that the study could have answered questions regarding potential drivers, but “they didn’t dig down into any of the factors that were associated with the poorer outcomes in the patients with rheumatoid arthritis and lupus and scleroderma.”
Indeed, the investigators acknowledge that the study lacked information on coronary anatomy, duration and severity of the autoimmune disease, imaging data, and medications such as anti-inflammatory or immune-targeted therapies.
Dr. Giles highlighted several factors that can contribute to a poorer post-MI prognosis in patients with rheumatic diseases; these include frailty, being more hypercoaguable, increased rates of myocardial dysfunction and other heart and blood vessel diseases, and chronic treatment with steroids and nonsteroidal anti-inflammatory drugs that often interferes with anticoagulation after a MI or when putting in a stent. “So, there’s lot of moving parts, and not one single thing that is likely the answer.”
In addition, he said, “there’s always going to be a portion of these patients who, despite doing the best that we can with treatment, are going to have very severe disease. That may or may not be the subset of patients that did the worst, but likely they’re overrepresented in those patients.”
Finally, the inability to move the needle may lie with the lack of evidence-based screening and management guidelines for cardiovascular disease in any rheumatic disease, Dr. Giles observed. “There’s no guideline for us to use to decide who needs screening over and above what’s recommended for the general population, and then, even if you do screen, what do you do other than what you would normally?”
Rheumatologists are often reluctant to take up the cardiovascular screening side of things because visits are short, and a lot of that time is spent trying to manage the inflammatory components of a patient’s disease, he said. There’s also a barrier in getting some patients to add a cardiologist to the mix of physicians they already see, especially if they don’t have any symptoms.
“If someone has had an event, it’s a lot easier for people to be convinced to go see the cardiologist, obviously, but prior to having an event, the preventative side of things is something that often gets missed or goes to the wayside,” Dr. Giles said.
The study was partly funded by philanthropic gifts by the Haslam family, Bailey family, and Khouri family to the Cleveland Clinic for coauthor Dr. Milind Desai’s research. Dr. Desai is a consultant for Medtronic and Bristol Myers Squibb and serves on an executive steering committee of a BMS-sponsored trial. The remaining authors report having no relevant disclosures. Dr. Giles is a consultant on drug cardiovascular safety for Pfizer, AbbVie, and Eli Lilly.
A version of this article first appeared on Medscape.com.
FROM JOURNAL OF THE AMERICAN HEART ASSOCIATION
FDA warns of clip lock malfunctions with MitraClip devices
The Food and Drug Administration is alerting health care providers about the potential for clip lock malfunctions with Abbott’s MitraClip’s delivery system.
“These events appear to occur in approximately 1.3% of MitraClip procedures and have been observed with all device models,” the FDA says in a letter posted on its website.
The MitraClip device was approved in 2013 for patients with symptomatic, degenerative mitral regurgitation (MR) deemed high risk for mitral-valve surgery.
In its own “urgent medical device correction letter” to providers, Abbott reports a recent increase in reports of the clips failing to “establish final arm angle (EFAA)” and of “clip opening while locked (COWL)” events.
During device preparation and prior to clip deployment, the operator intentionally attempts to open a locked clip to verify that the locking mechanism is engaged.
COWL describes when the clip arm angle increases postdeployment. “In these cases, users observe a slippage in the lock, resulting in an arm angle greater than 10 degrees from the angle observed at deployment,” which can be identified through fluoroscopy, Abbott says.
From February 2021 to January 2022, the EFAA failure rate was 0.51% and COWL rate 0.28%, increasing to 0.80% and 0.50%, respectively, from February 2022 to July 2022, according to the company.
Despite the increase in reports, the acute procedural success rate remains consistent with historical data, according to Abbott. “Further, EFAA failure or COWL most often results in no adverse patient outcomes. COWL may lead to less MR reduction, which is often treated with the use of one or more additional clips.”
Abbott says there is also a “low incidence” of required additional interventions. No immediate open surgical conversions have occurred as a result of EFAA/COWL events, whereas 0.53% of such events have resulted in nonurgent surgical conversions.
“In any case where significant residual MR is observed after clip deployment, a second clip should be considered and implanted in accordance with the IFU [instructions for use],” it advises.
Abbott says that a “change in the material properties of one of the clip locking components” has been identified as a contributing cause of EFAA/COWL events. It is working on producing new lots with updated manufacturing processing and raw material to mitigate the risk.
Certain use conditions can also contribute to EFAA/COWL events, and are referenced in the IFU, Appendix A, it notes.
The FDA is working with Abbott and recommends that health care providers do the following:
- Review the recall notice from Abbott for all MitraClip Clip Delivery Systems.
- Be aware of the potential for clip lock malfunctions before or after deployment with this device.
- Read and carefully follow the instructions for use and the recommendations provided in the recall notice to help minimize the chance of the clip failing to lock. These include recommendations about procedural steps for implant positioning, locking sequences, establishing clip arm angle, preparation for clip release, and avoiding excessive force and manipulation when unlocking the clip during device preparation and during the procedure.
Health care professionals can also report adverse reactions or quality problems they experience using these devices to the FDA’s MedWatch program.
A version of this article first appeared on Medscape.com.
The Food and Drug Administration is alerting health care providers about the potential for clip lock malfunctions with Abbott’s MitraClip’s delivery system.
“These events appear to occur in approximately 1.3% of MitraClip procedures and have been observed with all device models,” the FDA says in a letter posted on its website.
The MitraClip device was approved in 2013 for patients with symptomatic, degenerative mitral regurgitation (MR) deemed high risk for mitral-valve surgery.
In its own “urgent medical device correction letter” to providers, Abbott reports a recent increase in reports of the clips failing to “establish final arm angle (EFAA)” and of “clip opening while locked (COWL)” events.
During device preparation and prior to clip deployment, the operator intentionally attempts to open a locked clip to verify that the locking mechanism is engaged.
COWL describes when the clip arm angle increases postdeployment. “In these cases, users observe a slippage in the lock, resulting in an arm angle greater than 10 degrees from the angle observed at deployment,” which can be identified through fluoroscopy, Abbott says.
From February 2021 to January 2022, the EFAA failure rate was 0.51% and COWL rate 0.28%, increasing to 0.80% and 0.50%, respectively, from February 2022 to July 2022, according to the company.
Despite the increase in reports, the acute procedural success rate remains consistent with historical data, according to Abbott. “Further, EFAA failure or COWL most often results in no adverse patient outcomes. COWL may lead to less MR reduction, which is often treated with the use of one or more additional clips.”
Abbott says there is also a “low incidence” of required additional interventions. No immediate open surgical conversions have occurred as a result of EFAA/COWL events, whereas 0.53% of such events have resulted in nonurgent surgical conversions.
“In any case where significant residual MR is observed after clip deployment, a second clip should be considered and implanted in accordance with the IFU [instructions for use],” it advises.
Abbott says that a “change in the material properties of one of the clip locking components” has been identified as a contributing cause of EFAA/COWL events. It is working on producing new lots with updated manufacturing processing and raw material to mitigate the risk.
Certain use conditions can also contribute to EFAA/COWL events, and are referenced in the IFU, Appendix A, it notes.
The FDA is working with Abbott and recommends that health care providers do the following:
- Review the recall notice from Abbott for all MitraClip Clip Delivery Systems.
- Be aware of the potential for clip lock malfunctions before or after deployment with this device.
- Read and carefully follow the instructions for use and the recommendations provided in the recall notice to help minimize the chance of the clip failing to lock. These include recommendations about procedural steps for implant positioning, locking sequences, establishing clip arm angle, preparation for clip release, and avoiding excessive force and manipulation when unlocking the clip during device preparation and during the procedure.
Health care professionals can also report adverse reactions or quality problems they experience using these devices to the FDA’s MedWatch program.
A version of this article first appeared on Medscape.com.
The Food and Drug Administration is alerting health care providers about the potential for clip lock malfunctions with Abbott’s MitraClip’s delivery system.
“These events appear to occur in approximately 1.3% of MitraClip procedures and have been observed with all device models,” the FDA says in a letter posted on its website.
The MitraClip device was approved in 2013 for patients with symptomatic, degenerative mitral regurgitation (MR) deemed high risk for mitral-valve surgery.
In its own “urgent medical device correction letter” to providers, Abbott reports a recent increase in reports of the clips failing to “establish final arm angle (EFAA)” and of “clip opening while locked (COWL)” events.
During device preparation and prior to clip deployment, the operator intentionally attempts to open a locked clip to verify that the locking mechanism is engaged.
COWL describes when the clip arm angle increases postdeployment. “In these cases, users observe a slippage in the lock, resulting in an arm angle greater than 10 degrees from the angle observed at deployment,” which can be identified through fluoroscopy, Abbott says.
From February 2021 to January 2022, the EFAA failure rate was 0.51% and COWL rate 0.28%, increasing to 0.80% and 0.50%, respectively, from February 2022 to July 2022, according to the company.
Despite the increase in reports, the acute procedural success rate remains consistent with historical data, according to Abbott. “Further, EFAA failure or COWL most often results in no adverse patient outcomes. COWL may lead to less MR reduction, which is often treated with the use of one or more additional clips.”
Abbott says there is also a “low incidence” of required additional interventions. No immediate open surgical conversions have occurred as a result of EFAA/COWL events, whereas 0.53% of such events have resulted in nonurgent surgical conversions.
“In any case where significant residual MR is observed after clip deployment, a second clip should be considered and implanted in accordance with the IFU [instructions for use],” it advises.
Abbott says that a “change in the material properties of one of the clip locking components” has been identified as a contributing cause of EFAA/COWL events. It is working on producing new lots with updated manufacturing processing and raw material to mitigate the risk.
Certain use conditions can also contribute to EFAA/COWL events, and are referenced in the IFU, Appendix A, it notes.
The FDA is working with Abbott and recommends that health care providers do the following:
- Review the recall notice from Abbott for all MitraClip Clip Delivery Systems.
- Be aware of the potential for clip lock malfunctions before or after deployment with this device.
- Read and carefully follow the instructions for use and the recommendations provided in the recall notice to help minimize the chance of the clip failing to lock. These include recommendations about procedural steps for implant positioning, locking sequences, establishing clip arm angle, preparation for clip release, and avoiding excessive force and manipulation when unlocking the clip during device preparation and during the procedure.
Health care professionals can also report adverse reactions or quality problems they experience using these devices to the FDA’s MedWatch program.
A version of this article first appeared on Medscape.com.
Evolocumab benefits accrue with longer follow-up: FOURIER OLE
Long-term lipid lowering with evolocumab (Repatha) further reduces cardiovascular events, including CV death, without a safety signal, according to results from the FOURIER open-label extension (OLE) study.
In the parent FOURIER trial, treatment with the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor over a median of 2.2 years reduced the primary efficacy endpoint by 15% but showed no CV mortality signal, compared with placebo, in patients with atherosclerotic disease on background statin therapy.
Now with follow-up out to 8.4 years – the longest to date in any PCSK9 study – cardiovascular mortality was cut by 23% in patients who remained on evolocumab, compared with those originally assigned to placebo (3.32% vs. 4.45%; hazard ratio, 0.77; 95% confidence interval, 0.60-0.99).
The Kaplan-Meier curves during FOURIER were “essentially superimposed and it was not until the open-label extension period had begun with longer-term follow up that the benefit in terms of cardiovascular mortality reduction became apparent,” said principal investigator Michelle O’Donoghue, MD, MPH, of Brigham and Women’s Hospital, Boston.
The results were reported at the annual congress of the European Society of Cardiology and published simultaneously in Circulation.
Pivotal statin trials have median follow-up times of 4-5 years and demonstrated both a lag effect, meaning clinical benefit grew over time, and a legacy effect, where clinical benefit persisted in extended follow-up after the parent study, Dr. O’Donoghue observed.
With shorter follow-up in the parent FOURIER trial, there was evidence of a lag effect with the risk reduction in CV death, MI, and stroke increasing from 16% in the first year to 25% over time with evolocumab.
FOURIER-OLE enrolled 6,635 patients (3355 randomly assigned to evolocumab and 3280 to placebo), who completed the parent study and self-injected evolocumab subcutaneously with the choice of 140 mg every 2 weeks or 420 mg monthly. Study visits were at week 12 and then every 24 weeks. Median follow-up was 5 years.
Their mean age was 62 years, three-fourths were men, a third had diabetes. Three-fourths were on a high-intensity statin at the time of enrollment in FOURIER, and median LDL cholesterol at randomization was 91 mg/dL (2.4 mmol/L).
At week 12, the median LDL cholesterol was 30 mg/dL (0.78 mmol/L), and this was sustained throughout follow-up, Dr. O’Donoghue reported. Most patients achieved very low LDL cholesterol levels, with 63.2% achieving levels less than 40 mg/dL (1.04 mmol/L) and 26.6% less than 20 mg/dL (0.52 mmol/L).
Patients randomly assigned in the parent trial to evolocumab versus placebo had a 15% lower risk of the primary outcome of CV death, MI, stroke, hospitalization for unstable angina, or coronary revascularization (15.4% vs. 17.5%; HR, 0.85; 95% CI, 0.75-0.96).
Their risk of CV death, MI, or stroke was 20% lower (9.7% vs. 11.9%; HR, 0.80; 95% CI, 0.68-0.93), and, as noted previously, 23% lower for CV death.
When major adverse cardiovascular events data were parsed out by year, the largest LDL cholesterol reduction was in years 1 and 2 of the parent study (delta, 62 mg/dL between treatment arms), “highlighting that lag of benefit that continued to accrue with time,” Dr. O’Donoghue said.
“There was then carryover into the extension period, such that there was legacy effect from the LDL [cholesterol] delta that was seen during the parent study,” she said. “This benefit was most apparent early on during open-label extension and then, as one might expect when all patients were being treated with the same therapy, it began to attenuate somewhat with time.”
Although early studies raised concerns that very low LDL cholesterol may be associated with an increased risk of hemorrhagic stroke and neurocognitive effects, the frequency of adverse events did not increase over time with evolocumab exposure.
Annualized incidence rates for patients initially randomized to evolocumab did not exceed those for placebo-treated patients for any of the following events of interest: serious safety events (10% vs. 13%), hemorrhagic stroke (0.04% vs. 0.05%), new-onset diabetes (1.2% vs. 2.3%), muscle-related events (1.2% vs. 1.9%), injection-site reactions (0.4% vs. 0.7%), and drug-related allergic reactions (0.6% vs. 1.1%).
“Long-term use of evolocumab with a median follow-up of more than 7 years appears both safe and well tolerated,” Dr. O’Donoghue said.
Taken together with the continued accrual of cardiovascular benefit, including CV mortality, “these findings argue for early initiation of a marked and sustained LDL cholesterol reduction to maximize benefit,” she concluded.
Translating the benefits
Ulrich Laufs, MD, Leipzig (Germany) University Hospital, Germany, and invited commentator for the session, said the trial addresses two key issues: the long-term safety of low LDL cholesterol lowering and the long-term safety of inhibiting PCSK9, which is highly expressed not only in the liver but also in the brain, small intestine, and kidneys. Indeed, an LDL cholesterol level below 30 mg/dL is lower than the ESC treatment recommendation for very-high-risk patients and is, in fact, lower than most assays are reliable to interpret.
“So it is very important that we have these very clear data showing us that there were no adverse events, also including cataracts and hemorrhagic stroke, and these were on the level of placebo and did not increase over time,” he said.
The question of efficacy is triggered by observations of another PCSK9, the humanized monoclonal antibody bococizumab, which was associated in the SPIRE trial with an increase in LDL cholesterol over time because of neutralizing antibodies. Reassuringly, there was “completely sustained LDL [cholesterol] reduction” with no neutralizing antibodies with the fully human antibody evolocumab in FOURIER-OLE and in recent data from the OSLER-1 study, Dr. Laufs observed.
Acknowledging the potential for selection bias with an OLE program, Dr. Laufs said there are two important open questions: “Can the safety data observed for extracellular PCSK9 inhibition using an antibody be transferred to other mechanisms of PCSK9 inhibition? And obviously, from the perspective of patient care, how can we implement these important data into patient care and improve access to PCSK9 inhibitors?”
With regard to the latter point, he said physicians should be cautious in using the term “plaque regression,” opting instead for prevention and stabilization of atherosclerosis, and when using the term “legacy,” which may be misinterpreted by patients to imply there was cessation of therapy.
“From my perspective, [what] the open-label extension really shows is that earlier treatment is better,” Dr. Laufs said. “This should be our message.”
In a press conference prior to the presentation, ESC commentator Johann Bauersachs, MD, Hannover (Germany) Medical School, said “this is extremely important data because it confirms that it’s safe, and the criticism of the FOURIER study that mortality, cardiovascular mortality, was not reduced is now also reduced.”
Dr. Bauersachs said it would have been unethical to wait 7 years for a placebo-controlled trial and questioned whether data are available and suggestive of a legacy effect among patients who did not participate in the open-label extension.
Dr. O’Donoghue said unfortunately those data aren’t available but that Kaplan-Meier curves for the primary endpoint in the parent trial continued to diverge over time and that there was somewhat of a lag in terms of that divergence. “So, a median follow-up of 2 years may have been insufficient, especially for the emerging cardiovascular mortality that took longer to appear.”
The study was funded by Amgen. Dr. O’Donoghue reported receiving research grants from Amgen, AstraZeneca, Janssen, Intarcia, and Novartis, and consulting fees from Amgen, Novartis, AstraZeneca, and Janssen. Dr. Laufs reported receiving honoraria/reimbursement for lecture, study participation, and scientific cooperation with Saarland or Leipzig University, as well as relationships with multiple pharmaceutical and device makers.
A version of this article first appeared on Medscape.com.
Long-term lipid lowering with evolocumab (Repatha) further reduces cardiovascular events, including CV death, without a safety signal, according to results from the FOURIER open-label extension (OLE) study.
In the parent FOURIER trial, treatment with the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor over a median of 2.2 years reduced the primary efficacy endpoint by 15% but showed no CV mortality signal, compared with placebo, in patients with atherosclerotic disease on background statin therapy.
Now with follow-up out to 8.4 years – the longest to date in any PCSK9 study – cardiovascular mortality was cut by 23% in patients who remained on evolocumab, compared with those originally assigned to placebo (3.32% vs. 4.45%; hazard ratio, 0.77; 95% confidence interval, 0.60-0.99).
The Kaplan-Meier curves during FOURIER were “essentially superimposed and it was not until the open-label extension period had begun with longer-term follow up that the benefit in terms of cardiovascular mortality reduction became apparent,” said principal investigator Michelle O’Donoghue, MD, MPH, of Brigham and Women’s Hospital, Boston.
The results were reported at the annual congress of the European Society of Cardiology and published simultaneously in Circulation.
Pivotal statin trials have median follow-up times of 4-5 years and demonstrated both a lag effect, meaning clinical benefit grew over time, and a legacy effect, where clinical benefit persisted in extended follow-up after the parent study, Dr. O’Donoghue observed.
With shorter follow-up in the parent FOURIER trial, there was evidence of a lag effect with the risk reduction in CV death, MI, and stroke increasing from 16% in the first year to 25% over time with evolocumab.
FOURIER-OLE enrolled 6,635 patients (3355 randomly assigned to evolocumab and 3280 to placebo), who completed the parent study and self-injected evolocumab subcutaneously with the choice of 140 mg every 2 weeks or 420 mg monthly. Study visits were at week 12 and then every 24 weeks. Median follow-up was 5 years.
Their mean age was 62 years, three-fourths were men, a third had diabetes. Three-fourths were on a high-intensity statin at the time of enrollment in FOURIER, and median LDL cholesterol at randomization was 91 mg/dL (2.4 mmol/L).
At week 12, the median LDL cholesterol was 30 mg/dL (0.78 mmol/L), and this was sustained throughout follow-up, Dr. O’Donoghue reported. Most patients achieved very low LDL cholesterol levels, with 63.2% achieving levels less than 40 mg/dL (1.04 mmol/L) and 26.6% less than 20 mg/dL (0.52 mmol/L).
Patients randomly assigned in the parent trial to evolocumab versus placebo had a 15% lower risk of the primary outcome of CV death, MI, stroke, hospitalization for unstable angina, or coronary revascularization (15.4% vs. 17.5%; HR, 0.85; 95% CI, 0.75-0.96).
Their risk of CV death, MI, or stroke was 20% lower (9.7% vs. 11.9%; HR, 0.80; 95% CI, 0.68-0.93), and, as noted previously, 23% lower for CV death.
When major adverse cardiovascular events data were parsed out by year, the largest LDL cholesterol reduction was in years 1 and 2 of the parent study (delta, 62 mg/dL between treatment arms), “highlighting that lag of benefit that continued to accrue with time,” Dr. O’Donoghue said.
“There was then carryover into the extension period, such that there was legacy effect from the LDL [cholesterol] delta that was seen during the parent study,” she said. “This benefit was most apparent early on during open-label extension and then, as one might expect when all patients were being treated with the same therapy, it began to attenuate somewhat with time.”
Although early studies raised concerns that very low LDL cholesterol may be associated with an increased risk of hemorrhagic stroke and neurocognitive effects, the frequency of adverse events did not increase over time with evolocumab exposure.
Annualized incidence rates for patients initially randomized to evolocumab did not exceed those for placebo-treated patients for any of the following events of interest: serious safety events (10% vs. 13%), hemorrhagic stroke (0.04% vs. 0.05%), new-onset diabetes (1.2% vs. 2.3%), muscle-related events (1.2% vs. 1.9%), injection-site reactions (0.4% vs. 0.7%), and drug-related allergic reactions (0.6% vs. 1.1%).
“Long-term use of evolocumab with a median follow-up of more than 7 years appears both safe and well tolerated,” Dr. O’Donoghue said.
Taken together with the continued accrual of cardiovascular benefit, including CV mortality, “these findings argue for early initiation of a marked and sustained LDL cholesterol reduction to maximize benefit,” she concluded.
Translating the benefits
Ulrich Laufs, MD, Leipzig (Germany) University Hospital, Germany, and invited commentator for the session, said the trial addresses two key issues: the long-term safety of low LDL cholesterol lowering and the long-term safety of inhibiting PCSK9, which is highly expressed not only in the liver but also in the brain, small intestine, and kidneys. Indeed, an LDL cholesterol level below 30 mg/dL is lower than the ESC treatment recommendation for very-high-risk patients and is, in fact, lower than most assays are reliable to interpret.
“So it is very important that we have these very clear data showing us that there were no adverse events, also including cataracts and hemorrhagic stroke, and these were on the level of placebo and did not increase over time,” he said.
The question of efficacy is triggered by observations of another PCSK9, the humanized monoclonal antibody bococizumab, which was associated in the SPIRE trial with an increase in LDL cholesterol over time because of neutralizing antibodies. Reassuringly, there was “completely sustained LDL [cholesterol] reduction” with no neutralizing antibodies with the fully human antibody evolocumab in FOURIER-OLE and in recent data from the OSLER-1 study, Dr. Laufs observed.
Acknowledging the potential for selection bias with an OLE program, Dr. Laufs said there are two important open questions: “Can the safety data observed for extracellular PCSK9 inhibition using an antibody be transferred to other mechanisms of PCSK9 inhibition? And obviously, from the perspective of patient care, how can we implement these important data into patient care and improve access to PCSK9 inhibitors?”
With regard to the latter point, he said physicians should be cautious in using the term “plaque regression,” opting instead for prevention and stabilization of atherosclerosis, and when using the term “legacy,” which may be misinterpreted by patients to imply there was cessation of therapy.
“From my perspective, [what] the open-label extension really shows is that earlier treatment is better,” Dr. Laufs said. “This should be our message.”
In a press conference prior to the presentation, ESC commentator Johann Bauersachs, MD, Hannover (Germany) Medical School, said “this is extremely important data because it confirms that it’s safe, and the criticism of the FOURIER study that mortality, cardiovascular mortality, was not reduced is now also reduced.”
Dr. Bauersachs said it would have been unethical to wait 7 years for a placebo-controlled trial and questioned whether data are available and suggestive of a legacy effect among patients who did not participate in the open-label extension.
Dr. O’Donoghue said unfortunately those data aren’t available but that Kaplan-Meier curves for the primary endpoint in the parent trial continued to diverge over time and that there was somewhat of a lag in terms of that divergence. “So, a median follow-up of 2 years may have been insufficient, especially for the emerging cardiovascular mortality that took longer to appear.”
The study was funded by Amgen. Dr. O’Donoghue reported receiving research grants from Amgen, AstraZeneca, Janssen, Intarcia, and Novartis, and consulting fees from Amgen, Novartis, AstraZeneca, and Janssen. Dr. Laufs reported receiving honoraria/reimbursement for lecture, study participation, and scientific cooperation with Saarland or Leipzig University, as well as relationships with multiple pharmaceutical and device makers.
A version of this article first appeared on Medscape.com.
Long-term lipid lowering with evolocumab (Repatha) further reduces cardiovascular events, including CV death, without a safety signal, according to results from the FOURIER open-label extension (OLE) study.
In the parent FOURIER trial, treatment with the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor over a median of 2.2 years reduced the primary efficacy endpoint by 15% but showed no CV mortality signal, compared with placebo, in patients with atherosclerotic disease on background statin therapy.
Now with follow-up out to 8.4 years – the longest to date in any PCSK9 study – cardiovascular mortality was cut by 23% in patients who remained on evolocumab, compared with those originally assigned to placebo (3.32% vs. 4.45%; hazard ratio, 0.77; 95% confidence interval, 0.60-0.99).
The Kaplan-Meier curves during FOURIER were “essentially superimposed and it was not until the open-label extension period had begun with longer-term follow up that the benefit in terms of cardiovascular mortality reduction became apparent,” said principal investigator Michelle O’Donoghue, MD, MPH, of Brigham and Women’s Hospital, Boston.
The results were reported at the annual congress of the European Society of Cardiology and published simultaneously in Circulation.
Pivotal statin trials have median follow-up times of 4-5 years and demonstrated both a lag effect, meaning clinical benefit grew over time, and a legacy effect, where clinical benefit persisted in extended follow-up after the parent study, Dr. O’Donoghue observed.
With shorter follow-up in the parent FOURIER trial, there was evidence of a lag effect with the risk reduction in CV death, MI, and stroke increasing from 16% in the first year to 25% over time with evolocumab.
FOURIER-OLE enrolled 6,635 patients (3355 randomly assigned to evolocumab and 3280 to placebo), who completed the parent study and self-injected evolocumab subcutaneously with the choice of 140 mg every 2 weeks or 420 mg monthly. Study visits were at week 12 and then every 24 weeks. Median follow-up was 5 years.
Their mean age was 62 years, three-fourths were men, a third had diabetes. Three-fourths were on a high-intensity statin at the time of enrollment in FOURIER, and median LDL cholesterol at randomization was 91 mg/dL (2.4 mmol/L).
At week 12, the median LDL cholesterol was 30 mg/dL (0.78 mmol/L), and this was sustained throughout follow-up, Dr. O’Donoghue reported. Most patients achieved very low LDL cholesterol levels, with 63.2% achieving levels less than 40 mg/dL (1.04 mmol/L) and 26.6% less than 20 mg/dL (0.52 mmol/L).
Patients randomly assigned in the parent trial to evolocumab versus placebo had a 15% lower risk of the primary outcome of CV death, MI, stroke, hospitalization for unstable angina, or coronary revascularization (15.4% vs. 17.5%; HR, 0.85; 95% CI, 0.75-0.96).
Their risk of CV death, MI, or stroke was 20% lower (9.7% vs. 11.9%; HR, 0.80; 95% CI, 0.68-0.93), and, as noted previously, 23% lower for CV death.
When major adverse cardiovascular events data were parsed out by year, the largest LDL cholesterol reduction was in years 1 and 2 of the parent study (delta, 62 mg/dL between treatment arms), “highlighting that lag of benefit that continued to accrue with time,” Dr. O’Donoghue said.
“There was then carryover into the extension period, such that there was legacy effect from the LDL [cholesterol] delta that was seen during the parent study,” she said. “This benefit was most apparent early on during open-label extension and then, as one might expect when all patients were being treated with the same therapy, it began to attenuate somewhat with time.”
Although early studies raised concerns that very low LDL cholesterol may be associated with an increased risk of hemorrhagic stroke and neurocognitive effects, the frequency of adverse events did not increase over time with evolocumab exposure.
Annualized incidence rates for patients initially randomized to evolocumab did not exceed those for placebo-treated patients for any of the following events of interest: serious safety events (10% vs. 13%), hemorrhagic stroke (0.04% vs. 0.05%), new-onset diabetes (1.2% vs. 2.3%), muscle-related events (1.2% vs. 1.9%), injection-site reactions (0.4% vs. 0.7%), and drug-related allergic reactions (0.6% vs. 1.1%).
“Long-term use of evolocumab with a median follow-up of more than 7 years appears both safe and well tolerated,” Dr. O’Donoghue said.
Taken together with the continued accrual of cardiovascular benefit, including CV mortality, “these findings argue for early initiation of a marked and sustained LDL cholesterol reduction to maximize benefit,” she concluded.
Translating the benefits
Ulrich Laufs, MD, Leipzig (Germany) University Hospital, Germany, and invited commentator for the session, said the trial addresses two key issues: the long-term safety of low LDL cholesterol lowering and the long-term safety of inhibiting PCSK9, which is highly expressed not only in the liver but also in the brain, small intestine, and kidneys. Indeed, an LDL cholesterol level below 30 mg/dL is lower than the ESC treatment recommendation for very-high-risk patients and is, in fact, lower than most assays are reliable to interpret.
“So it is very important that we have these very clear data showing us that there were no adverse events, also including cataracts and hemorrhagic stroke, and these were on the level of placebo and did not increase over time,” he said.
The question of efficacy is triggered by observations of another PCSK9, the humanized monoclonal antibody bococizumab, which was associated in the SPIRE trial with an increase in LDL cholesterol over time because of neutralizing antibodies. Reassuringly, there was “completely sustained LDL [cholesterol] reduction” with no neutralizing antibodies with the fully human antibody evolocumab in FOURIER-OLE and in recent data from the OSLER-1 study, Dr. Laufs observed.
Acknowledging the potential for selection bias with an OLE program, Dr. Laufs said there are two important open questions: “Can the safety data observed for extracellular PCSK9 inhibition using an antibody be transferred to other mechanisms of PCSK9 inhibition? And obviously, from the perspective of patient care, how can we implement these important data into patient care and improve access to PCSK9 inhibitors?”
With regard to the latter point, he said physicians should be cautious in using the term “plaque regression,” opting instead for prevention and stabilization of atherosclerosis, and when using the term “legacy,” which may be misinterpreted by patients to imply there was cessation of therapy.
“From my perspective, [what] the open-label extension really shows is that earlier treatment is better,” Dr. Laufs said. “This should be our message.”
In a press conference prior to the presentation, ESC commentator Johann Bauersachs, MD, Hannover (Germany) Medical School, said “this is extremely important data because it confirms that it’s safe, and the criticism of the FOURIER study that mortality, cardiovascular mortality, was not reduced is now also reduced.”
Dr. Bauersachs said it would have been unethical to wait 7 years for a placebo-controlled trial and questioned whether data are available and suggestive of a legacy effect among patients who did not participate in the open-label extension.
Dr. O’Donoghue said unfortunately those data aren’t available but that Kaplan-Meier curves for the primary endpoint in the parent trial continued to diverge over time and that there was somewhat of a lag in terms of that divergence. “So, a median follow-up of 2 years may have been insufficient, especially for the emerging cardiovascular mortality that took longer to appear.”
The study was funded by Amgen. Dr. O’Donoghue reported receiving research grants from Amgen, AstraZeneca, Janssen, Intarcia, and Novartis, and consulting fees from Amgen, Novartis, AstraZeneca, and Janssen. Dr. Laufs reported receiving honoraria/reimbursement for lecture, study participation, and scientific cooperation with Saarland or Leipzig University, as well as relationships with multiple pharmaceutical and device makers.
A version of this article first appeared on Medscape.com.
FROM ESC CONGRESS 2022
Rivaroxaban outmatched by VKAs for AFib in rheumatic heart disease
Contrary to expectations, vitamin K antagonists (VKAs) reduced the risk for ischemic stroke and death, compared with the factor Xa inhibitor rivaroxaban, (Xarelto, Janssen) in patients with rheumatic heart disease and atrial fibrillation (AFib), in the INVICTUS trial.
Patients receiving a VKA, typically warfarin, had a 25% lower risk for the primary outcome – a composite of stroke, systemic embolism, myocardial infarction, or death from vascular or unknown causes outcome – than receiving rivaroxaban (hazard ratio, 1.25; 95% confidence interval, 1.10-1.41).
This difference was driven primarily by a significant reduction in the risk for death in the VKA group, and without a significant increase in major bleeding, reported Ganesan Karthikeyan, MD, from the All India Institute of Medical Sciences in New Delhi.
“VKA should remain the standard of care for patients with rheumatic heart disease and atrial fibrillation,” he concluded in a hotline session at the annual congress of the European Society of Cardiology.
The study, simultaneously published in the New England Journal of Medicine, is the first randomized controlled trial to assess anticoagulant therapy in patients with rheumatic heart disease and AFib.
“Who could have possibly guessed these results? Certainly not me,” said invited discussant Renato D. Lopes, MD, MHS, PhD, Duke Clinical Research Institute, Durham, N.C. “To me, this is one more classical example of why we need to do randomized trials, since they are the only reliable way to determine treatment effects and drive clinical practice.”
Evidence gap
Rheumatic heart disease affects over 40 million people, mainly living in low- and low- to middle-income countries. About 20% of symptomatic patients have AF and an elevated stroke risk, but previous AFib trials excluded these patients, Dr. Karthikeyan noted.
INVICTUS was led by the Population Health Research Institute in Hamilton, Ont., and enrolled 4,565 patients from 24 countries in Africa, Asia, and Latin America who had rheumatic heart disease, AFib or atrial flutter, and an increased stroke risk caused by any of the following: CHA2DS2VASc score of 2 or more, moderate to severe mitral stenosis (valve area ≤ 2.0 cm2), left atrial spontaneous echo contrast, or left atrial thrombus.
Participants were randomly assigned to receive rivaroxaban, 20 mg once daily (15 mg/d if creatinine clearance was 15-49 mL/min), or a VKA titrated to an international normalized ratio (INR) of 2.0-3.0.
Warfarin was used in 79%-85% of patients assigned to VKA, with the percentage varying between visits. The INR was in therapeutic range in 33.2% of patients at baseline, 65.1% at 3 years, and 64.1% at 4 years.
During an average follow-up of 3.1 years, the primary outcome occurred in 446 patients in the VKA group (6.49% per year) and 560 patients in the rivaroxaban group (8.21% per year). The restricted mean survival time for the primary outcome was 1,675 vs. 1,599 days, respectively (difference, –76 days; 95% CI, –121 to –31 days; P for superiority < .001).
The rate of stroke or systemic embolism was similar between the VKA and rivaroxaban groups (75 vs. 94 events), although ischemic strokes were significantly lower with VKA (48 vs. 74 events).
No easy explanation
Deaths were significantly lower with VKA than rivaroxaban, at 442 versus 552 (restricted mean survival time for death, 1,608 vs. 1,587 days; difference, −72 days; 95% CI, –117 to –28 days).
“This reduction is not easily explained,” Dr. Karthikeyan acknowledged. “We cannot explain this reduction by the reduction in stroke that we saw because the number of deaths that are prevented by VKA are far larger than the number of strokes that are prevented. Moreover, the number of deaths were mainly heart failure or sudden deaths.”
Numbers of patients with major bleeding were also similar in the VKA and rivaroxaban groups (56 vs. 40 patients; P = .18), although numbers with fatal bleeding were lower with rivaroxaban (15 vs. 4, respectively).
By design, there were more physician interactions for monthly monitoring of INR in the VKA group, “but we do not believe such a large reduction can be explained entirely by increased health care contact,” he said. Moreover, there was no significant between-group difference in heart failure medications or hospitalizations or the need for valve replacement.
Almost a quarter (23%) of patients in the rivaroxaban group permanently discontinued the study drug versus just 6% in the VKA group.
Importantly, the mortality benefit emerged much later than in other trials and coincided with the time when the INR became therapeutic at about 3 years, Dr. Karthikeyan said. But it is unknown whether this is because of the INR or an unrelated effect.
More physician contact
Following the presentation, session cochair C. Michael Gibson, MD, Baim Institute for Clinical Research, Harvard Medical School, Boston, questioned the 23% discontinuation rate for rivaroxaban. “Is this really a superiority of warfarin or is this superiority of having someone come in and see their physician for a lot of checks on their INR?”
In response, Dr. Karthikeyan said that permanent discontinuation rates were about 20%-25% in shorter-duration direct oral anticoagulant trials, such as RELY, ROCKET-AF, and ARISTOLE, and exceeded 30% in ENGAGE-AF with 2.8 years’ follow-up.
“So, this is not new,” he said, adding that 31.4% of rivaroxaban patients did so for valve replacement surgery and subsequently received nonstudy VKA.
Dr. Lopes said it is important to keep in mind that INVICTUS enrolled a “very different population” that was younger (mean age, 50.5 years), was much more often female (72.3%), and had fewer comorbidities than patients with AFib who did not have rheumatic heart disease in the pivotal trials.
“It will be interesting to see the treatment effect according to mitral stenosis severity, since we had about 30% with mild mitral stenosis and additionally 18% of patients without mitral stenosis,” he added.
Co–principal investigator Stuart J. Connolly, MD, from the Population Health Research Institute, said physician contacts may be a factor but that the mortality difference was clear, highly significant, and sufficiently powered.
“What’s amazing is that what we’re seeing here is something that hasn’t been previously described with VKA or warfarin, which is that it reduces mortality,” he said in an interview.
Rivaroxaban has never been shown to reduce mortality in any particular condition, and a meta-analysis of other novel oral anticoagulants shows only a small reduction in mortality, caused almost completely by less intracranial hemorrhage than warfarin, he added. “So, we don’t think this is a problem with rivaroxaban. In some ways, rivaroxaban is an innocent bystander to a trial of warfarin in patients with rheumatic heart disease and atrial fibrillation.”
Dr. Connolly said more work is needed to explain the findings and analyses are planned to see which patients are at highest risk for death as well as looking at the relationship between INR control and outcomes.
“We need to do more research on what it is about VKA that could explain this,” he said. “Is it affecting the myocardium in some way, is it preventing fibrosis, is there some off target effect, not on the anticoagulation system, that could explain this?”
Athena Poppas, MD, chief of cardiology at Brown University, Providence, R.I., and past president of the American College of Cardiology, said “INVICTUS is an incredibly important study that needed to be done.”
“The results – though disappointing and surprising in some ways – I don’t think we can explain them away and change what we are doing right now,” she said in an interview.
Although warfarin is a cheap drug, Dr. Poppas said, it would be tremendously helpful to have an alternative treatment for these patients. Mechanistic studies are needed to understand the observed mortality advantage and low bleeding rates but that trials of other novel anticoagulants are also needed.
“But I’m not sure that will happen,” she added. “It’s unlikely to be industry sponsored, so it would be a very expensive lift with a low likelihood of success.”
In an editorial accompanying the paper, Gregory Y.H. Lip, MD, University of Liverpool (England), pointed out that observational data show similar or even higher risks for major bleeding with rivaroxaban than with warfarin. “To improve outcomes in these patients, we therefore need to look beyond anticoagulation alone or beyond a type of anticoagulation drug per se. Indeed, a one-size-fits-all approach may not be appropriate.”
The study was funded by an unrestricted grant from Bayer. Dr. Karthikeyan and Dr. Poppas reported no relevant conflicts of interest.
A version of this article first appeared on Medscape.com.
Contrary to expectations, vitamin K antagonists (VKAs) reduced the risk for ischemic stroke and death, compared with the factor Xa inhibitor rivaroxaban, (Xarelto, Janssen) in patients with rheumatic heart disease and atrial fibrillation (AFib), in the INVICTUS trial.
Patients receiving a VKA, typically warfarin, had a 25% lower risk for the primary outcome – a composite of stroke, systemic embolism, myocardial infarction, or death from vascular or unknown causes outcome – than receiving rivaroxaban (hazard ratio, 1.25; 95% confidence interval, 1.10-1.41).
This difference was driven primarily by a significant reduction in the risk for death in the VKA group, and without a significant increase in major bleeding, reported Ganesan Karthikeyan, MD, from the All India Institute of Medical Sciences in New Delhi.
“VKA should remain the standard of care for patients with rheumatic heart disease and atrial fibrillation,” he concluded in a hotline session at the annual congress of the European Society of Cardiology.
The study, simultaneously published in the New England Journal of Medicine, is the first randomized controlled trial to assess anticoagulant therapy in patients with rheumatic heart disease and AFib.
“Who could have possibly guessed these results? Certainly not me,” said invited discussant Renato D. Lopes, MD, MHS, PhD, Duke Clinical Research Institute, Durham, N.C. “To me, this is one more classical example of why we need to do randomized trials, since they are the only reliable way to determine treatment effects and drive clinical practice.”
Evidence gap
Rheumatic heart disease affects over 40 million people, mainly living in low- and low- to middle-income countries. About 20% of symptomatic patients have AF and an elevated stroke risk, but previous AFib trials excluded these patients, Dr. Karthikeyan noted.
INVICTUS was led by the Population Health Research Institute in Hamilton, Ont., and enrolled 4,565 patients from 24 countries in Africa, Asia, and Latin America who had rheumatic heart disease, AFib or atrial flutter, and an increased stroke risk caused by any of the following: CHA2DS2VASc score of 2 or more, moderate to severe mitral stenosis (valve area ≤ 2.0 cm2), left atrial spontaneous echo contrast, or left atrial thrombus.
Participants were randomly assigned to receive rivaroxaban, 20 mg once daily (15 mg/d if creatinine clearance was 15-49 mL/min), or a VKA titrated to an international normalized ratio (INR) of 2.0-3.0.
Warfarin was used in 79%-85% of patients assigned to VKA, with the percentage varying between visits. The INR was in therapeutic range in 33.2% of patients at baseline, 65.1% at 3 years, and 64.1% at 4 years.
During an average follow-up of 3.1 years, the primary outcome occurred in 446 patients in the VKA group (6.49% per year) and 560 patients in the rivaroxaban group (8.21% per year). The restricted mean survival time for the primary outcome was 1,675 vs. 1,599 days, respectively (difference, –76 days; 95% CI, –121 to –31 days; P for superiority < .001).
The rate of stroke or systemic embolism was similar between the VKA and rivaroxaban groups (75 vs. 94 events), although ischemic strokes were significantly lower with VKA (48 vs. 74 events).
No easy explanation
Deaths were significantly lower with VKA than rivaroxaban, at 442 versus 552 (restricted mean survival time for death, 1,608 vs. 1,587 days; difference, −72 days; 95% CI, –117 to –28 days).
“This reduction is not easily explained,” Dr. Karthikeyan acknowledged. “We cannot explain this reduction by the reduction in stroke that we saw because the number of deaths that are prevented by VKA are far larger than the number of strokes that are prevented. Moreover, the number of deaths were mainly heart failure or sudden deaths.”
Numbers of patients with major bleeding were also similar in the VKA and rivaroxaban groups (56 vs. 40 patients; P = .18), although numbers with fatal bleeding were lower with rivaroxaban (15 vs. 4, respectively).
By design, there were more physician interactions for monthly monitoring of INR in the VKA group, “but we do not believe such a large reduction can be explained entirely by increased health care contact,” he said. Moreover, there was no significant between-group difference in heart failure medications or hospitalizations or the need for valve replacement.
Almost a quarter (23%) of patients in the rivaroxaban group permanently discontinued the study drug versus just 6% in the VKA group.
Importantly, the mortality benefit emerged much later than in other trials and coincided with the time when the INR became therapeutic at about 3 years, Dr. Karthikeyan said. But it is unknown whether this is because of the INR or an unrelated effect.
More physician contact
Following the presentation, session cochair C. Michael Gibson, MD, Baim Institute for Clinical Research, Harvard Medical School, Boston, questioned the 23% discontinuation rate for rivaroxaban. “Is this really a superiority of warfarin or is this superiority of having someone come in and see their physician for a lot of checks on their INR?”
In response, Dr. Karthikeyan said that permanent discontinuation rates were about 20%-25% in shorter-duration direct oral anticoagulant trials, such as RELY, ROCKET-AF, and ARISTOLE, and exceeded 30% in ENGAGE-AF with 2.8 years’ follow-up.
“So, this is not new,” he said, adding that 31.4% of rivaroxaban patients did so for valve replacement surgery and subsequently received nonstudy VKA.
Dr. Lopes said it is important to keep in mind that INVICTUS enrolled a “very different population” that was younger (mean age, 50.5 years), was much more often female (72.3%), and had fewer comorbidities than patients with AFib who did not have rheumatic heart disease in the pivotal trials.
“It will be interesting to see the treatment effect according to mitral stenosis severity, since we had about 30% with mild mitral stenosis and additionally 18% of patients without mitral stenosis,” he added.
Co–principal investigator Stuart J. Connolly, MD, from the Population Health Research Institute, said physician contacts may be a factor but that the mortality difference was clear, highly significant, and sufficiently powered.
“What’s amazing is that what we’re seeing here is something that hasn’t been previously described with VKA or warfarin, which is that it reduces mortality,” he said in an interview.
Rivaroxaban has never been shown to reduce mortality in any particular condition, and a meta-analysis of other novel oral anticoagulants shows only a small reduction in mortality, caused almost completely by less intracranial hemorrhage than warfarin, he added. “So, we don’t think this is a problem with rivaroxaban. In some ways, rivaroxaban is an innocent bystander to a trial of warfarin in patients with rheumatic heart disease and atrial fibrillation.”
Dr. Connolly said more work is needed to explain the findings and analyses are planned to see which patients are at highest risk for death as well as looking at the relationship between INR control and outcomes.
“We need to do more research on what it is about VKA that could explain this,” he said. “Is it affecting the myocardium in some way, is it preventing fibrosis, is there some off target effect, not on the anticoagulation system, that could explain this?”
Athena Poppas, MD, chief of cardiology at Brown University, Providence, R.I., and past president of the American College of Cardiology, said “INVICTUS is an incredibly important study that needed to be done.”
“The results – though disappointing and surprising in some ways – I don’t think we can explain them away and change what we are doing right now,” she said in an interview.
Although warfarin is a cheap drug, Dr. Poppas said, it would be tremendously helpful to have an alternative treatment for these patients. Mechanistic studies are needed to understand the observed mortality advantage and low bleeding rates but that trials of other novel anticoagulants are also needed.
“But I’m not sure that will happen,” she added. “It’s unlikely to be industry sponsored, so it would be a very expensive lift with a low likelihood of success.”
In an editorial accompanying the paper, Gregory Y.H. Lip, MD, University of Liverpool (England), pointed out that observational data show similar or even higher risks for major bleeding with rivaroxaban than with warfarin. “To improve outcomes in these patients, we therefore need to look beyond anticoagulation alone or beyond a type of anticoagulation drug per se. Indeed, a one-size-fits-all approach may not be appropriate.”
The study was funded by an unrestricted grant from Bayer. Dr. Karthikeyan and Dr. Poppas reported no relevant conflicts of interest.
A version of this article first appeared on Medscape.com.
Contrary to expectations, vitamin K antagonists (VKAs) reduced the risk for ischemic stroke and death, compared with the factor Xa inhibitor rivaroxaban, (Xarelto, Janssen) in patients with rheumatic heart disease and atrial fibrillation (AFib), in the INVICTUS trial.
Patients receiving a VKA, typically warfarin, had a 25% lower risk for the primary outcome – a composite of stroke, systemic embolism, myocardial infarction, or death from vascular or unknown causes outcome – than receiving rivaroxaban (hazard ratio, 1.25; 95% confidence interval, 1.10-1.41).
This difference was driven primarily by a significant reduction in the risk for death in the VKA group, and without a significant increase in major bleeding, reported Ganesan Karthikeyan, MD, from the All India Institute of Medical Sciences in New Delhi.
“VKA should remain the standard of care for patients with rheumatic heart disease and atrial fibrillation,” he concluded in a hotline session at the annual congress of the European Society of Cardiology.
The study, simultaneously published in the New England Journal of Medicine, is the first randomized controlled trial to assess anticoagulant therapy in patients with rheumatic heart disease and AFib.
“Who could have possibly guessed these results? Certainly not me,” said invited discussant Renato D. Lopes, MD, MHS, PhD, Duke Clinical Research Institute, Durham, N.C. “To me, this is one more classical example of why we need to do randomized trials, since they are the only reliable way to determine treatment effects and drive clinical practice.”
Evidence gap
Rheumatic heart disease affects over 40 million people, mainly living in low- and low- to middle-income countries. About 20% of symptomatic patients have AF and an elevated stroke risk, but previous AFib trials excluded these patients, Dr. Karthikeyan noted.
INVICTUS was led by the Population Health Research Institute in Hamilton, Ont., and enrolled 4,565 patients from 24 countries in Africa, Asia, and Latin America who had rheumatic heart disease, AFib or atrial flutter, and an increased stroke risk caused by any of the following: CHA2DS2VASc score of 2 or more, moderate to severe mitral stenosis (valve area ≤ 2.0 cm2), left atrial spontaneous echo contrast, or left atrial thrombus.
Participants were randomly assigned to receive rivaroxaban, 20 mg once daily (15 mg/d if creatinine clearance was 15-49 mL/min), or a VKA titrated to an international normalized ratio (INR) of 2.0-3.0.
Warfarin was used in 79%-85% of patients assigned to VKA, with the percentage varying between visits. The INR was in therapeutic range in 33.2% of patients at baseline, 65.1% at 3 years, and 64.1% at 4 years.
During an average follow-up of 3.1 years, the primary outcome occurred in 446 patients in the VKA group (6.49% per year) and 560 patients in the rivaroxaban group (8.21% per year). The restricted mean survival time for the primary outcome was 1,675 vs. 1,599 days, respectively (difference, –76 days; 95% CI, –121 to –31 days; P for superiority < .001).
The rate of stroke or systemic embolism was similar between the VKA and rivaroxaban groups (75 vs. 94 events), although ischemic strokes were significantly lower with VKA (48 vs. 74 events).
No easy explanation
Deaths were significantly lower with VKA than rivaroxaban, at 442 versus 552 (restricted mean survival time for death, 1,608 vs. 1,587 days; difference, −72 days; 95% CI, –117 to –28 days).
“This reduction is not easily explained,” Dr. Karthikeyan acknowledged. “We cannot explain this reduction by the reduction in stroke that we saw because the number of deaths that are prevented by VKA are far larger than the number of strokes that are prevented. Moreover, the number of deaths were mainly heart failure or sudden deaths.”
Numbers of patients with major bleeding were also similar in the VKA and rivaroxaban groups (56 vs. 40 patients; P = .18), although numbers with fatal bleeding were lower with rivaroxaban (15 vs. 4, respectively).
By design, there were more physician interactions for monthly monitoring of INR in the VKA group, “but we do not believe such a large reduction can be explained entirely by increased health care contact,” he said. Moreover, there was no significant between-group difference in heart failure medications or hospitalizations or the need for valve replacement.
Almost a quarter (23%) of patients in the rivaroxaban group permanently discontinued the study drug versus just 6% in the VKA group.
Importantly, the mortality benefit emerged much later than in other trials and coincided with the time when the INR became therapeutic at about 3 years, Dr. Karthikeyan said. But it is unknown whether this is because of the INR or an unrelated effect.
More physician contact
Following the presentation, session cochair C. Michael Gibson, MD, Baim Institute for Clinical Research, Harvard Medical School, Boston, questioned the 23% discontinuation rate for rivaroxaban. “Is this really a superiority of warfarin or is this superiority of having someone come in and see their physician for a lot of checks on their INR?”
In response, Dr. Karthikeyan said that permanent discontinuation rates were about 20%-25% in shorter-duration direct oral anticoagulant trials, such as RELY, ROCKET-AF, and ARISTOLE, and exceeded 30% in ENGAGE-AF with 2.8 years’ follow-up.
“So, this is not new,” he said, adding that 31.4% of rivaroxaban patients did so for valve replacement surgery and subsequently received nonstudy VKA.
Dr. Lopes said it is important to keep in mind that INVICTUS enrolled a “very different population” that was younger (mean age, 50.5 years), was much more often female (72.3%), and had fewer comorbidities than patients with AFib who did not have rheumatic heart disease in the pivotal trials.
“It will be interesting to see the treatment effect according to mitral stenosis severity, since we had about 30% with mild mitral stenosis and additionally 18% of patients without mitral stenosis,” he added.
Co–principal investigator Stuart J. Connolly, MD, from the Population Health Research Institute, said physician contacts may be a factor but that the mortality difference was clear, highly significant, and sufficiently powered.
“What’s amazing is that what we’re seeing here is something that hasn’t been previously described with VKA or warfarin, which is that it reduces mortality,” he said in an interview.
Rivaroxaban has never been shown to reduce mortality in any particular condition, and a meta-analysis of other novel oral anticoagulants shows only a small reduction in mortality, caused almost completely by less intracranial hemorrhage than warfarin, he added. “So, we don’t think this is a problem with rivaroxaban. In some ways, rivaroxaban is an innocent bystander to a trial of warfarin in patients with rheumatic heart disease and atrial fibrillation.”
Dr. Connolly said more work is needed to explain the findings and analyses are planned to see which patients are at highest risk for death as well as looking at the relationship between INR control and outcomes.
“We need to do more research on what it is about VKA that could explain this,” he said. “Is it affecting the myocardium in some way, is it preventing fibrosis, is there some off target effect, not on the anticoagulation system, that could explain this?”
Athena Poppas, MD, chief of cardiology at Brown University, Providence, R.I., and past president of the American College of Cardiology, said “INVICTUS is an incredibly important study that needed to be done.”
“The results – though disappointing and surprising in some ways – I don’t think we can explain them away and change what we are doing right now,” she said in an interview.
Although warfarin is a cheap drug, Dr. Poppas said, it would be tremendously helpful to have an alternative treatment for these patients. Mechanistic studies are needed to understand the observed mortality advantage and low bleeding rates but that trials of other novel anticoagulants are also needed.
“But I’m not sure that will happen,” she added. “It’s unlikely to be industry sponsored, so it would be a very expensive lift with a low likelihood of success.”
In an editorial accompanying the paper, Gregory Y.H. Lip, MD, University of Liverpool (England), pointed out that observational data show similar or even higher risks for major bleeding with rivaroxaban than with warfarin. “To improve outcomes in these patients, we therefore need to look beyond anticoagulation alone or beyond a type of anticoagulation drug per se. Indeed, a one-size-fits-all approach may not be appropriate.”
The study was funded by an unrestricted grant from Bayer. Dr. Karthikeyan and Dr. Poppas reported no relevant conflicts of interest.
A version of this article first appeared on Medscape.com.
FROM ESC CONGRESS 2022
PCI fails to beat OMT in ischemic cardiomyopathy: REVIVED-BCIS2
Percutaneous coronary intervention (PCI) with optimal medical therapy (OMT) does not prolong survival or improve ventricular function, compared with OMT alone, in patients with severe ischemic cardiomyopathy, according to results from the REVIVED-BCIS2 trial.
The primary composite outcome of all-cause death or heart failure hospitalization occurred in 37.2% of the PCI group and 38% of the OMT group (hazard ratio, 0.99; P = .96) over a median of 3.4 years follow-up. The treatment effect was consistent across all subgroups.
There were no significant differences in left ventricular ejection fraction (LVEF) at 6 and 12 months.
Quality of life scores favored PCI early on, but there was catch-up over time with medical therapy, and this advantage disappeared by 2 years, principal investigator Divaka Perera, MD, King’s College London, reported at the annual congress of the European Society of Cardiology.
“The takeaway is that we should not be offering PCI to patients who have stable, well-medicated left ventricular dysfunction,” Dr. Perera told this news organization. “But we should still consider revascularization in patients presenting with acute coronary syndromes or who have lots of angina, because they were not included in the trial.”
The study, published simultaneously in the New England Journal of Medicine, provides the first randomized evidence on PCI for ischemic cardiomyopathy.
Revascularization guidelines in the United States make no recommendation for PCI, whereas those in Europe recommend coronary artery bypass grafting (CABG) first for patients with multivessel disease (class 1); they have a class 2a, level of evidence C indication for PCI in select patients. U.S. and European heart failure guidelines also support guideline directed therapy and CABG in select patients with ejection fractions of 35% or less.
This guidance is based on consensus opinion and the STICH trial, in which CABG plus OMT failed to provide a mortality benefit over OMT alone at 5 years but improved survival at 10 years in the extension STICHES study.
“Medical therapy for heart failure works, and this trial’s results are another important reminder of that,” said Eric Velazquez, MD, who led STICH and was invited to comment on the findings.
Mortality will only get better with the use of SGLT2 inhibitors, he noted, which were not included in the trial. Utilization of ACE inhibitors/ARBs/ARNIs and beta-blockers was similar to STICH and excellent in REVIVED. “They did do a better job in utilization of ICD and CRTs than the STICH trial, and I think that needs to be explored further about the impact of those changes.”
Nevertheless, ischemic cardiomyopathy patients have “unacceptably high mortality,” with the observed mortality about 20% at 3 years and about 35% at 5 years, said Dr. Velazquez, with Yale University, New Haven, Conn.
In most heart failure trials, HF hospitalization drives the primary composite endpoint, but the opposite was true here and in STICH, he observed. “You had twice the risk of dying during the 3.4 years than you did of being hospitalized for heart failure, and ... that is [an important] distinction we must realize is evident in our ischemic cardiomyopathy patients.”
The findings will likely not lead to a change in the guidelines, he added. “I think we continue as status quo for now and get more data.”
Despite the lack of randomized evidence, he cautioned that PCI is increasingly performed in patients with ischemic cardiomyopathy, with registry data suggesting nearly 60% of patients received the procedure.
Reached for comment, Clyde Yancy, MD, chief of cardiology and vice dean of diversity & inclusion at Northwestern University Feinberg School of Medicine, Chicago, said, “For now, the current guidelines are correct. Best application of guideline-directed medical and device therapy is the gold standard for heart failure, and that includes heart failure due to ischemic etiologies.
“Do these data resolve the question of revascularization in the setting of coronary disease and reduced EF heart failure? Hardly,” he added. “Clinical judgment must prevail, and where appropriate, coronary revascularization remains a consideration. But it is not a panacea.”
Detailed results
Between August 2013 and March 2020, REVIVED-BCIS2 enrolled 700 patients at 40 U.K. centers who had an LVEF of 35% or less, extensive CAD (defined by a British Cardiovascular Intervention Society myocardial Jeopardy Score [BCIS-JS] of at least 6), and viability in at least four myocardial segments amenable to PCI. Patients were evenly randomly assigned to individually adjusted pharmacologic and device therapy for heart failure alone or with PCI.
The average age was about 70, only 12.3% women, 344 patients had 2-vessel CAD, and 281 had 3-vessel CAD. The mean LVEF was 27% and median BCIS-JS score 10.
During follow-up, which reached 8.5 years in some patients due to the long enrollment, 31.7% of patients in the PCI group and 32.6% patients in the OMT group died from any cause and 14.7% and 15.3%, respectively, were admitted for heart failure.
LVEF improved by 1.8% at 6 months and 2% at 12 months in the PCI group and by 3.4% and 1.1%, respectively, in the OMT group. The mean between-group difference was –1.6% at 6 months and 0.9% at 12 months.
With regard to quality of life, the Kansas City Cardiomyopathy Questionnaire overall summary score favored the PCI group by 6.5 points at 6 months and by 4.5 points at 12 months, but by 24 months the between-group difference was 2.6 points (95% confidence interval, –0.7 to 5.8). Scores on the EuroQol Group 5-Dimensions 5-Level Questionnaire followed a similar pattern.
Unplanned revascularization was more common in the OMT group (HR, 0.27; 95% CI, 0.13-0.53). Acute myocardial infarction rates were similar in the two groups (HR, 1.01, 95% CI, 0.64-1.60), with the PCI group having more periprocedural infarcts and slightly fewer spontaneous infarcts.
Possible reasons for the discordant results between STICH and REVIVED are the threefold excess mortality within 30 days of CABG, whereas no such early hit occurred with PCI, lead investigator Dr. Perera said in an interview. Medical therapy has also evolved over time and REVIVED enrolled a more “real-world” population, with a median age close to 70 years versus 59 in STICH.
‘Modest’ degree of CAD?
An accompanying editorial, however, points out that despite considerable ventricular dysfunction, about half the patients in REVIVED had only 2-vessel disease and a median of two lesions treated.
“This relatively modest degree of coronary artery disease seems unusual for patients selected to undergo revascularization with the hope of restoring or normalizing ventricular function,” writes Ajay Kirtane, MD, from Columbia University Irving Medical Center, NewYork-Presbyterian Hospital.
He said more details are needed on completeness of the revascularization, severity of stenosis, physiologic assessment of the lesion and, “most importantly, the correlation of stenosis with previous ischemic or viability testing.”
Asked about the editorial, Dr. Perera agreed that information on the type of revascularization and myocardial viability are important and said they hope to share analyses of the only recently unblinded data at the American College of Cardiology meeting next spring. Importantly, about 71% of viability testing was done by cardiac MR and the rest largely by dobutamine stress echocardiogram.
He disagreed, however, that participants had relatively modest CAD based on the 2- or 3-vessel classification and said the median score on the more granular BCIS-JS was 10, with maximum 12 indicating the entire myocardium is supplied by diseased vessels.
The trial also included almost 100 patients with left main disease, a group not included in previous medical therapy trials, including STICH and ISCHEMIA, Dr. Perera noted. “So, I think it was pretty, pretty severe coronary disease but a cohort that was better treated medically.”
George Dangas, MD, PhD, a professor of medicine at Icahn School of Medicine at Mount Sinai, New York, said the study provides valuable information but also expressed concerns that the chronic heart failure in the trial was much more advanced than the CAD.
“Symptoms are low level, and this is predominantly related to CHF, and if you manage the CHF the best way with advanced therapies, assist device or transplant or any other way, that might take priority over the CAD lesions,” said Dr. Dangas, who was not associated with REVIVED. “I would expect CAD lesions would have more importance if we move into the class 3 or higher of symptomatology, and, again in this study, that was not [present] in over 70% of the patients.”
The study was funded by the National Institute for Health and Care Research’s Health Technology Assessment Program. Dr. Perera, Dr. Velazquez, and Dr. Dangas report no relevant financial relationships.
Dr. Kirtane reports grants, nonfinancial support and other from Medtronic, Abbott Vascular, Boston Scientific, Abiomed, CathWorks, Siemens, Philips, ReCor Medical, Cardiovascular Systems, Amgen, and Chiesi. He reports grants and other from Neurotronic, Magental Medical, Canon, SoniVie, Shockwave Medical, and Merck. He also reports nonfinancial support from Opsens, Zoll, Regeneron, Biotronik, and Bolt Medical, and personal fees from IMDS.
A version of this article first appeared on Medscape.com.
Percutaneous coronary intervention (PCI) with optimal medical therapy (OMT) does not prolong survival or improve ventricular function, compared with OMT alone, in patients with severe ischemic cardiomyopathy, according to results from the REVIVED-BCIS2 trial.
The primary composite outcome of all-cause death or heart failure hospitalization occurred in 37.2% of the PCI group and 38% of the OMT group (hazard ratio, 0.99; P = .96) over a median of 3.4 years follow-up. The treatment effect was consistent across all subgroups.
There were no significant differences in left ventricular ejection fraction (LVEF) at 6 and 12 months.
Quality of life scores favored PCI early on, but there was catch-up over time with medical therapy, and this advantage disappeared by 2 years, principal investigator Divaka Perera, MD, King’s College London, reported at the annual congress of the European Society of Cardiology.
“The takeaway is that we should not be offering PCI to patients who have stable, well-medicated left ventricular dysfunction,” Dr. Perera told this news organization. “But we should still consider revascularization in patients presenting with acute coronary syndromes or who have lots of angina, because they were not included in the trial.”
The study, published simultaneously in the New England Journal of Medicine, provides the first randomized evidence on PCI for ischemic cardiomyopathy.
Revascularization guidelines in the United States make no recommendation for PCI, whereas those in Europe recommend coronary artery bypass grafting (CABG) first for patients with multivessel disease (class 1); they have a class 2a, level of evidence C indication for PCI in select patients. U.S. and European heart failure guidelines also support guideline directed therapy and CABG in select patients with ejection fractions of 35% or less.
This guidance is based on consensus opinion and the STICH trial, in which CABG plus OMT failed to provide a mortality benefit over OMT alone at 5 years but improved survival at 10 years in the extension STICHES study.
“Medical therapy for heart failure works, and this trial’s results are another important reminder of that,” said Eric Velazquez, MD, who led STICH and was invited to comment on the findings.
Mortality will only get better with the use of SGLT2 inhibitors, he noted, which were not included in the trial. Utilization of ACE inhibitors/ARBs/ARNIs and beta-blockers was similar to STICH and excellent in REVIVED. “They did do a better job in utilization of ICD and CRTs than the STICH trial, and I think that needs to be explored further about the impact of those changes.”
Nevertheless, ischemic cardiomyopathy patients have “unacceptably high mortality,” with the observed mortality about 20% at 3 years and about 35% at 5 years, said Dr. Velazquez, with Yale University, New Haven, Conn.
In most heart failure trials, HF hospitalization drives the primary composite endpoint, but the opposite was true here and in STICH, he observed. “You had twice the risk of dying during the 3.4 years than you did of being hospitalized for heart failure, and ... that is [an important] distinction we must realize is evident in our ischemic cardiomyopathy patients.”
The findings will likely not lead to a change in the guidelines, he added. “I think we continue as status quo for now and get more data.”
Despite the lack of randomized evidence, he cautioned that PCI is increasingly performed in patients with ischemic cardiomyopathy, with registry data suggesting nearly 60% of patients received the procedure.
Reached for comment, Clyde Yancy, MD, chief of cardiology and vice dean of diversity & inclusion at Northwestern University Feinberg School of Medicine, Chicago, said, “For now, the current guidelines are correct. Best application of guideline-directed medical and device therapy is the gold standard for heart failure, and that includes heart failure due to ischemic etiologies.
“Do these data resolve the question of revascularization in the setting of coronary disease and reduced EF heart failure? Hardly,” he added. “Clinical judgment must prevail, and where appropriate, coronary revascularization remains a consideration. But it is not a panacea.”
Detailed results
Between August 2013 and March 2020, REVIVED-BCIS2 enrolled 700 patients at 40 U.K. centers who had an LVEF of 35% or less, extensive CAD (defined by a British Cardiovascular Intervention Society myocardial Jeopardy Score [BCIS-JS] of at least 6), and viability in at least four myocardial segments amenable to PCI. Patients were evenly randomly assigned to individually adjusted pharmacologic and device therapy for heart failure alone or with PCI.
The average age was about 70, only 12.3% women, 344 patients had 2-vessel CAD, and 281 had 3-vessel CAD. The mean LVEF was 27% and median BCIS-JS score 10.
During follow-up, which reached 8.5 years in some patients due to the long enrollment, 31.7% of patients in the PCI group and 32.6% patients in the OMT group died from any cause and 14.7% and 15.3%, respectively, were admitted for heart failure.
LVEF improved by 1.8% at 6 months and 2% at 12 months in the PCI group and by 3.4% and 1.1%, respectively, in the OMT group. The mean between-group difference was –1.6% at 6 months and 0.9% at 12 months.
With regard to quality of life, the Kansas City Cardiomyopathy Questionnaire overall summary score favored the PCI group by 6.5 points at 6 months and by 4.5 points at 12 months, but by 24 months the between-group difference was 2.6 points (95% confidence interval, –0.7 to 5.8). Scores on the EuroQol Group 5-Dimensions 5-Level Questionnaire followed a similar pattern.
Unplanned revascularization was more common in the OMT group (HR, 0.27; 95% CI, 0.13-0.53). Acute myocardial infarction rates were similar in the two groups (HR, 1.01, 95% CI, 0.64-1.60), with the PCI group having more periprocedural infarcts and slightly fewer spontaneous infarcts.
Possible reasons for the discordant results between STICH and REVIVED are the threefold excess mortality within 30 days of CABG, whereas no such early hit occurred with PCI, lead investigator Dr. Perera said in an interview. Medical therapy has also evolved over time and REVIVED enrolled a more “real-world” population, with a median age close to 70 years versus 59 in STICH.
‘Modest’ degree of CAD?
An accompanying editorial, however, points out that despite considerable ventricular dysfunction, about half the patients in REVIVED had only 2-vessel disease and a median of two lesions treated.
“This relatively modest degree of coronary artery disease seems unusual for patients selected to undergo revascularization with the hope of restoring or normalizing ventricular function,” writes Ajay Kirtane, MD, from Columbia University Irving Medical Center, NewYork-Presbyterian Hospital.
He said more details are needed on completeness of the revascularization, severity of stenosis, physiologic assessment of the lesion and, “most importantly, the correlation of stenosis with previous ischemic or viability testing.”
Asked about the editorial, Dr. Perera agreed that information on the type of revascularization and myocardial viability are important and said they hope to share analyses of the only recently unblinded data at the American College of Cardiology meeting next spring. Importantly, about 71% of viability testing was done by cardiac MR and the rest largely by dobutamine stress echocardiogram.
He disagreed, however, that participants had relatively modest CAD based on the 2- or 3-vessel classification and said the median score on the more granular BCIS-JS was 10, with maximum 12 indicating the entire myocardium is supplied by diseased vessels.
The trial also included almost 100 patients with left main disease, a group not included in previous medical therapy trials, including STICH and ISCHEMIA, Dr. Perera noted. “So, I think it was pretty, pretty severe coronary disease but a cohort that was better treated medically.”
George Dangas, MD, PhD, a professor of medicine at Icahn School of Medicine at Mount Sinai, New York, said the study provides valuable information but also expressed concerns that the chronic heart failure in the trial was much more advanced than the CAD.
“Symptoms are low level, and this is predominantly related to CHF, and if you manage the CHF the best way with advanced therapies, assist device or transplant or any other way, that might take priority over the CAD lesions,” said Dr. Dangas, who was not associated with REVIVED. “I would expect CAD lesions would have more importance if we move into the class 3 or higher of symptomatology, and, again in this study, that was not [present] in over 70% of the patients.”
The study was funded by the National Institute for Health and Care Research’s Health Technology Assessment Program. Dr. Perera, Dr. Velazquez, and Dr. Dangas report no relevant financial relationships.
Dr. Kirtane reports grants, nonfinancial support and other from Medtronic, Abbott Vascular, Boston Scientific, Abiomed, CathWorks, Siemens, Philips, ReCor Medical, Cardiovascular Systems, Amgen, and Chiesi. He reports grants and other from Neurotronic, Magental Medical, Canon, SoniVie, Shockwave Medical, and Merck. He also reports nonfinancial support from Opsens, Zoll, Regeneron, Biotronik, and Bolt Medical, and personal fees from IMDS.
A version of this article first appeared on Medscape.com.
Percutaneous coronary intervention (PCI) with optimal medical therapy (OMT) does not prolong survival or improve ventricular function, compared with OMT alone, in patients with severe ischemic cardiomyopathy, according to results from the REVIVED-BCIS2 trial.
The primary composite outcome of all-cause death or heart failure hospitalization occurred in 37.2% of the PCI group and 38% of the OMT group (hazard ratio, 0.99; P = .96) over a median of 3.4 years follow-up. The treatment effect was consistent across all subgroups.
There were no significant differences in left ventricular ejection fraction (LVEF) at 6 and 12 months.
Quality of life scores favored PCI early on, but there was catch-up over time with medical therapy, and this advantage disappeared by 2 years, principal investigator Divaka Perera, MD, King’s College London, reported at the annual congress of the European Society of Cardiology.
“The takeaway is that we should not be offering PCI to patients who have stable, well-medicated left ventricular dysfunction,” Dr. Perera told this news organization. “But we should still consider revascularization in patients presenting with acute coronary syndromes or who have lots of angina, because they were not included in the trial.”
The study, published simultaneously in the New England Journal of Medicine, provides the first randomized evidence on PCI for ischemic cardiomyopathy.
Revascularization guidelines in the United States make no recommendation for PCI, whereas those in Europe recommend coronary artery bypass grafting (CABG) first for patients with multivessel disease (class 1); they have a class 2a, level of evidence C indication for PCI in select patients. U.S. and European heart failure guidelines also support guideline directed therapy and CABG in select patients with ejection fractions of 35% or less.
This guidance is based on consensus opinion and the STICH trial, in which CABG plus OMT failed to provide a mortality benefit over OMT alone at 5 years but improved survival at 10 years in the extension STICHES study.
“Medical therapy for heart failure works, and this trial’s results are another important reminder of that,” said Eric Velazquez, MD, who led STICH and was invited to comment on the findings.
Mortality will only get better with the use of SGLT2 inhibitors, he noted, which were not included in the trial. Utilization of ACE inhibitors/ARBs/ARNIs and beta-blockers was similar to STICH and excellent in REVIVED. “They did do a better job in utilization of ICD and CRTs than the STICH trial, and I think that needs to be explored further about the impact of those changes.”
Nevertheless, ischemic cardiomyopathy patients have “unacceptably high mortality,” with the observed mortality about 20% at 3 years and about 35% at 5 years, said Dr. Velazquez, with Yale University, New Haven, Conn.
In most heart failure trials, HF hospitalization drives the primary composite endpoint, but the opposite was true here and in STICH, he observed. “You had twice the risk of dying during the 3.4 years than you did of being hospitalized for heart failure, and ... that is [an important] distinction we must realize is evident in our ischemic cardiomyopathy patients.”
The findings will likely not lead to a change in the guidelines, he added. “I think we continue as status quo for now and get more data.”
Despite the lack of randomized evidence, he cautioned that PCI is increasingly performed in patients with ischemic cardiomyopathy, with registry data suggesting nearly 60% of patients received the procedure.
Reached for comment, Clyde Yancy, MD, chief of cardiology and vice dean of diversity & inclusion at Northwestern University Feinberg School of Medicine, Chicago, said, “For now, the current guidelines are correct. Best application of guideline-directed medical and device therapy is the gold standard for heart failure, and that includes heart failure due to ischemic etiologies.
“Do these data resolve the question of revascularization in the setting of coronary disease and reduced EF heart failure? Hardly,” he added. “Clinical judgment must prevail, and where appropriate, coronary revascularization remains a consideration. But it is not a panacea.”
Detailed results
Between August 2013 and March 2020, REVIVED-BCIS2 enrolled 700 patients at 40 U.K. centers who had an LVEF of 35% or less, extensive CAD (defined by a British Cardiovascular Intervention Society myocardial Jeopardy Score [BCIS-JS] of at least 6), and viability in at least four myocardial segments amenable to PCI. Patients were evenly randomly assigned to individually adjusted pharmacologic and device therapy for heart failure alone or with PCI.
The average age was about 70, only 12.3% women, 344 patients had 2-vessel CAD, and 281 had 3-vessel CAD. The mean LVEF was 27% and median BCIS-JS score 10.
During follow-up, which reached 8.5 years in some patients due to the long enrollment, 31.7% of patients in the PCI group and 32.6% patients in the OMT group died from any cause and 14.7% and 15.3%, respectively, were admitted for heart failure.
LVEF improved by 1.8% at 6 months and 2% at 12 months in the PCI group and by 3.4% and 1.1%, respectively, in the OMT group. The mean between-group difference was –1.6% at 6 months and 0.9% at 12 months.
With regard to quality of life, the Kansas City Cardiomyopathy Questionnaire overall summary score favored the PCI group by 6.5 points at 6 months and by 4.5 points at 12 months, but by 24 months the between-group difference was 2.6 points (95% confidence interval, –0.7 to 5.8). Scores on the EuroQol Group 5-Dimensions 5-Level Questionnaire followed a similar pattern.
Unplanned revascularization was more common in the OMT group (HR, 0.27; 95% CI, 0.13-0.53). Acute myocardial infarction rates were similar in the two groups (HR, 1.01, 95% CI, 0.64-1.60), with the PCI group having more periprocedural infarcts and slightly fewer spontaneous infarcts.
Possible reasons for the discordant results between STICH and REVIVED are the threefold excess mortality within 30 days of CABG, whereas no such early hit occurred with PCI, lead investigator Dr. Perera said in an interview. Medical therapy has also evolved over time and REVIVED enrolled a more “real-world” population, with a median age close to 70 years versus 59 in STICH.
‘Modest’ degree of CAD?
An accompanying editorial, however, points out that despite considerable ventricular dysfunction, about half the patients in REVIVED had only 2-vessel disease and a median of two lesions treated.
“This relatively modest degree of coronary artery disease seems unusual for patients selected to undergo revascularization with the hope of restoring or normalizing ventricular function,” writes Ajay Kirtane, MD, from Columbia University Irving Medical Center, NewYork-Presbyterian Hospital.
He said more details are needed on completeness of the revascularization, severity of stenosis, physiologic assessment of the lesion and, “most importantly, the correlation of stenosis with previous ischemic or viability testing.”
Asked about the editorial, Dr. Perera agreed that information on the type of revascularization and myocardial viability are important and said they hope to share analyses of the only recently unblinded data at the American College of Cardiology meeting next spring. Importantly, about 71% of viability testing was done by cardiac MR and the rest largely by dobutamine stress echocardiogram.
He disagreed, however, that participants had relatively modest CAD based on the 2- or 3-vessel classification and said the median score on the more granular BCIS-JS was 10, with maximum 12 indicating the entire myocardium is supplied by diseased vessels.
The trial also included almost 100 patients with left main disease, a group not included in previous medical therapy trials, including STICH and ISCHEMIA, Dr. Perera noted. “So, I think it was pretty, pretty severe coronary disease but a cohort that was better treated medically.”
George Dangas, MD, PhD, a professor of medicine at Icahn School of Medicine at Mount Sinai, New York, said the study provides valuable information but also expressed concerns that the chronic heart failure in the trial was much more advanced than the CAD.
“Symptoms are low level, and this is predominantly related to CHF, and if you manage the CHF the best way with advanced therapies, assist device or transplant or any other way, that might take priority over the CAD lesions,” said Dr. Dangas, who was not associated with REVIVED. “I would expect CAD lesions would have more importance if we move into the class 3 or higher of symptomatology, and, again in this study, that was not [present] in over 70% of the patients.”
The study was funded by the National Institute for Health and Care Research’s Health Technology Assessment Program. Dr. Perera, Dr. Velazquez, and Dr. Dangas report no relevant financial relationships.
Dr. Kirtane reports grants, nonfinancial support and other from Medtronic, Abbott Vascular, Boston Scientific, Abiomed, CathWorks, Siemens, Philips, ReCor Medical, Cardiovascular Systems, Amgen, and Chiesi. He reports grants and other from Neurotronic, Magental Medical, Canon, SoniVie, Shockwave Medical, and Merck. He also reports nonfinancial support from Opsens, Zoll, Regeneron, Biotronik, and Bolt Medical, and personal fees from IMDS.
A version of this article first appeared on Medscape.com.
FROM ESC CONGRESS 2022