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Managing agitation in outpatient dementia
NEW ORLEANS – A reasonable stepwise approach to pharmacotherapy for agitation in outpatient dementia begins with a judiciously chosen SSRI as first-line therapy, with the second-line consisting of augmentation with a benzodiazepine, M. Philip Luber, MD, said at the annual meeting of the American College of Physicians.
If this combination doesn’t provide satisfactory improvement after adequate dosing for sufficient duration, only then is it time to turn to an atypical antipsychotic agent as a higher-risk/higher-reward third-line therapy, added Dr. Luber, professor of psychiatry and associate dean for graduate medical education at the University of Texas, San Antonio.
He emphasized, however, that medications are not the first-line therapy for agitation in outpatients with dementia. That distinction belongs to psychosocial interventions.
“Utilize a social worker to assist the family in modifying the environment: family settings and people, regular routines, consistently orienting the patient, keeping stimulation at a low to moderate level. When that’s done right, it can really dampen down a lot of agitation,” he said.
Dr. Luber noted that the formal randomized trial evidence base for SSRIs as first-line pharmacotherapy and benzodiazepines as second-line is quite limited. But in conversations with geriatric psychiatrists and other health care professionals around the country who are working in this area, he has found broad agreement that this is a good strategy.
“A lot of folks don’t realize that [SSRIs] are actually very useful in the treatment of agitation in dementia. But you want to choose one with fewer side effects and drug-drug interactions,” Dr. Luber said.
Two SSRIs that fit the bill are escitalopram (Lexapro) and sertraline (Zoloft). Start low and increase the dose slowly, provided circumstances allow. Expect a therapeutic response to emerge in weeks, not days. And, in this elderly population, be sure to monitor for hyponatremia.
When considering augmentation, remember that “using benzodiazepines in the elderly is controversial, particularly with agitation in dementia. There is very little randomized clinical trial data on benzodiazepines in dementia. Actually, though, there are lots of clinical trials of benzodiazepines in dementia that feature benzodiazepines as rescue medication. So, clinically, there’s an awareness that the drugs work, but they haven’t been studied except as rescue medication,” he explained.
The phenomenon of paradoxical agitation occurring in elderly patients on benzodiazepines “is something to be careful about, but in fact it’s pretty uncommon. Just watch for it,” he added.
Dr. Luber is among many geriatric psychiatrists who preferentially turn to clonazepam (Klonopin) because its relatively long half-life allows for twice-daily administration.
“Think about using it regularly rather than PRN. You want to stay ahead of the agitation rather than behind it,” he advised.
Patients with liver disease are better served by a shorter-acting benzodiazepine such as lorazepam (Ativan), which is not oxidized in the liver.
Also controversial is use of atypical antipsychotics as third-line pharmacotherapy, “but many geriatric psychiatrists would agree with me that the next step if the patient is still agitated despite an SSRI augmented with a benzodiazepine is to consider a trial of an atypical antipsychotic,” Dr. Luber said.
He pointed to risperidone (Risperdal) and aripiprazole (Abilify) as agents with a good track record for treatment of agitation in dementia. He urged primary care physicians to be familiar with the risk of serious and even potentially fatal side effects as described in the black box warning.
“There are tough choices involved in treating patients with this disorder. Use shared decision making with the patient or family,” Dr. Luber said.
He reported having no financial conflicts of interest regarding his presentation.
NEW ORLEANS – A reasonable stepwise approach to pharmacotherapy for agitation in outpatient dementia begins with a judiciously chosen SSRI as first-line therapy, with the second-line consisting of augmentation with a benzodiazepine, M. Philip Luber, MD, said at the annual meeting of the American College of Physicians.
If this combination doesn’t provide satisfactory improvement after adequate dosing for sufficient duration, only then is it time to turn to an atypical antipsychotic agent as a higher-risk/higher-reward third-line therapy, added Dr. Luber, professor of psychiatry and associate dean for graduate medical education at the University of Texas, San Antonio.
He emphasized, however, that medications are not the first-line therapy for agitation in outpatients with dementia. That distinction belongs to psychosocial interventions.
“Utilize a social worker to assist the family in modifying the environment: family settings and people, regular routines, consistently orienting the patient, keeping stimulation at a low to moderate level. When that’s done right, it can really dampen down a lot of agitation,” he said.
Dr. Luber noted that the formal randomized trial evidence base for SSRIs as first-line pharmacotherapy and benzodiazepines as second-line is quite limited. But in conversations with geriatric psychiatrists and other health care professionals around the country who are working in this area, he has found broad agreement that this is a good strategy.
“A lot of folks don’t realize that [SSRIs] are actually very useful in the treatment of agitation in dementia. But you want to choose one with fewer side effects and drug-drug interactions,” Dr. Luber said.
Two SSRIs that fit the bill are escitalopram (Lexapro) and sertraline (Zoloft). Start low and increase the dose slowly, provided circumstances allow. Expect a therapeutic response to emerge in weeks, not days. And, in this elderly population, be sure to monitor for hyponatremia.
When considering augmentation, remember that “using benzodiazepines in the elderly is controversial, particularly with agitation in dementia. There is very little randomized clinical trial data on benzodiazepines in dementia. Actually, though, there are lots of clinical trials of benzodiazepines in dementia that feature benzodiazepines as rescue medication. So, clinically, there’s an awareness that the drugs work, but they haven’t been studied except as rescue medication,” he explained.
The phenomenon of paradoxical agitation occurring in elderly patients on benzodiazepines “is something to be careful about, but in fact it’s pretty uncommon. Just watch for it,” he added.
Dr. Luber is among many geriatric psychiatrists who preferentially turn to clonazepam (Klonopin) because its relatively long half-life allows for twice-daily administration.
“Think about using it regularly rather than PRN. You want to stay ahead of the agitation rather than behind it,” he advised.
Patients with liver disease are better served by a shorter-acting benzodiazepine such as lorazepam (Ativan), which is not oxidized in the liver.
Also controversial is use of atypical antipsychotics as third-line pharmacotherapy, “but many geriatric psychiatrists would agree with me that the next step if the patient is still agitated despite an SSRI augmented with a benzodiazepine is to consider a trial of an atypical antipsychotic,” Dr. Luber said.
He pointed to risperidone (Risperdal) and aripiprazole (Abilify) as agents with a good track record for treatment of agitation in dementia. He urged primary care physicians to be familiar with the risk of serious and even potentially fatal side effects as described in the black box warning.
“There are tough choices involved in treating patients with this disorder. Use shared decision making with the patient or family,” Dr. Luber said.
He reported having no financial conflicts of interest regarding his presentation.
NEW ORLEANS – A reasonable stepwise approach to pharmacotherapy for agitation in outpatient dementia begins with a judiciously chosen SSRI as first-line therapy, with the second-line consisting of augmentation with a benzodiazepine, M. Philip Luber, MD, said at the annual meeting of the American College of Physicians.
If this combination doesn’t provide satisfactory improvement after adequate dosing for sufficient duration, only then is it time to turn to an atypical antipsychotic agent as a higher-risk/higher-reward third-line therapy, added Dr. Luber, professor of psychiatry and associate dean for graduate medical education at the University of Texas, San Antonio.
He emphasized, however, that medications are not the first-line therapy for agitation in outpatients with dementia. That distinction belongs to psychosocial interventions.
“Utilize a social worker to assist the family in modifying the environment: family settings and people, regular routines, consistently orienting the patient, keeping stimulation at a low to moderate level. When that’s done right, it can really dampen down a lot of agitation,” he said.
Dr. Luber noted that the formal randomized trial evidence base for SSRIs as first-line pharmacotherapy and benzodiazepines as second-line is quite limited. But in conversations with geriatric psychiatrists and other health care professionals around the country who are working in this area, he has found broad agreement that this is a good strategy.
“A lot of folks don’t realize that [SSRIs] are actually very useful in the treatment of agitation in dementia. But you want to choose one with fewer side effects and drug-drug interactions,” Dr. Luber said.
Two SSRIs that fit the bill are escitalopram (Lexapro) and sertraline (Zoloft). Start low and increase the dose slowly, provided circumstances allow. Expect a therapeutic response to emerge in weeks, not days. And, in this elderly population, be sure to monitor for hyponatremia.
When considering augmentation, remember that “using benzodiazepines in the elderly is controversial, particularly with agitation in dementia. There is very little randomized clinical trial data on benzodiazepines in dementia. Actually, though, there are lots of clinical trials of benzodiazepines in dementia that feature benzodiazepines as rescue medication. So, clinically, there’s an awareness that the drugs work, but they haven’t been studied except as rescue medication,” he explained.
The phenomenon of paradoxical agitation occurring in elderly patients on benzodiazepines “is something to be careful about, but in fact it’s pretty uncommon. Just watch for it,” he added.
Dr. Luber is among many geriatric psychiatrists who preferentially turn to clonazepam (Klonopin) because its relatively long half-life allows for twice-daily administration.
“Think about using it regularly rather than PRN. You want to stay ahead of the agitation rather than behind it,” he advised.
Patients with liver disease are better served by a shorter-acting benzodiazepine such as lorazepam (Ativan), which is not oxidized in the liver.
Also controversial is use of atypical antipsychotics as third-line pharmacotherapy, “but many geriatric psychiatrists would agree with me that the next step if the patient is still agitated despite an SSRI augmented with a benzodiazepine is to consider a trial of an atypical antipsychotic,” Dr. Luber said.
He pointed to risperidone (Risperdal) and aripiprazole (Abilify) as agents with a good track record for treatment of agitation in dementia. He urged primary care physicians to be familiar with the risk of serious and even potentially fatal side effects as described in the black box warning.
“There are tough choices involved in treating patients with this disorder. Use shared decision making with the patient or family,” Dr. Luber said.
He reported having no financial conflicts of interest regarding his presentation.
REPORTING FROM ACP INTERNAL MEDICINE
Mask provides effective, cheap protection from hazardous electrocautery plumes
CHICAGO – Routine use of an N95 mask during electrocautery is an effective and inexpensive way for dermatologic surgeons to protect themselves from toxic, airborne particulate matter in the smoke generated during the procedure, Emily de Golian, MD, said at the annual meeting of the American College of Mohs Surgery.
“Our data suggest clear as well as superiority to the laser masks that are used in hair removal procedures and ablative procedures in cosmetic clinics,” commented Dr. de Golian, a Mohs micrographic surgery fellow at the University of California, San Diego.
This matter of self-protection from the effects of electrocautery smoke plumes deserves greater attention from the dermatologic community, according to Dr. de Golian. There is solid evidence that these plumes contain high concentrations of known carcinogens, including benzene, acetonitrile, and butadiene – indeed, concentrations far in excess of what’s found in second-hand cigarette smoke. Moreover, many of these airborne carcinogens and other toxins have been linked to leukemia, neurologic disorders, lung cancer, thrombotic disorders, lung disease, and infectious disease transmission, albeit not convincingly so to date in dermatologic surgeons. But why wait for definitive evidence to accrue?
“In light of these hazards – and according to governmental guidelines – dermatologic surgeons would be wise to adopt protective measures during surgical procedures,” Dr. de Golian said.
But they haven’t. She cited a national survey conducted several years ago by a colleague in which 79% of the 316 responding dermatologic surgeons indicated they use no smoke management whatsoever, neither masks nor a local exhaust evacuation system. Only 10% employed smoke management 25%-50% of the time during electrocautery, and a scant 11% of dermatologic surgeons did so at least 75% of the time (Dermatol Surg. 2014 Dec;40[12]:1373-7).
Given the far more substantial expense of installing an office smoke evacuation system, mask filtration becomes an attractive alternative. But the relative efficacy of the various types of masks in blocking fine and ultrafine particulate matter contained in electrocautery plumes hadn’t previously been systematically studied. This created the impetus for Dr. de Golian’s study.
The N95 masks were the clear winner, particularly when it came to filtering the ultrafine particles, which are of greatest concern because they remain suspended in air longer and penetrate deeper into the respiratory tract than larger particles. The N95 masks proved superior to procedural masks, which in turn were significantly more effective than the laser masks. The differences between mask performance for larger particle filtration were smaller, although the N95 remained number one. She noted that the study results probably underestimate the true filtration efficacy of N95 masks, since they form a tighter seal with the face in clinical practice than with the other two mask types.
Mask self-protection “is easily applicable in your own practice, and it meets NIOSH-recommended [National Institute for Occupational Safety and Health] standards for safety in the workplace,” the dermatologist noted.
In the next phase of her research, she plans to evaluate the optimal technology and techniques of smoke evacuation in the surgical suite. That’s an attractive method because it protects everyone in the room, not just the surgeon. And while the practitioner survey indicates this technology isn’t widely used by dermatologic surgeons on a routine basis at present, that could change, particularly in the current era in which patient-reported outcomes and satisfaction surveys have taken on added weight.
“Patients prefer not smelling their own tissue burning,” Dr. de Golian said.
She reported no financial conflicts regarding her study, which was conducted free of commercial support.
CHICAGO – Routine use of an N95 mask during electrocautery is an effective and inexpensive way for dermatologic surgeons to protect themselves from toxic, airborne particulate matter in the smoke generated during the procedure, Emily de Golian, MD, said at the annual meeting of the American College of Mohs Surgery.
“Our data suggest clear as well as superiority to the laser masks that are used in hair removal procedures and ablative procedures in cosmetic clinics,” commented Dr. de Golian, a Mohs micrographic surgery fellow at the University of California, San Diego.
This matter of self-protection from the effects of electrocautery smoke plumes deserves greater attention from the dermatologic community, according to Dr. de Golian. There is solid evidence that these plumes contain high concentrations of known carcinogens, including benzene, acetonitrile, and butadiene – indeed, concentrations far in excess of what’s found in second-hand cigarette smoke. Moreover, many of these airborne carcinogens and other toxins have been linked to leukemia, neurologic disorders, lung cancer, thrombotic disorders, lung disease, and infectious disease transmission, albeit not convincingly so to date in dermatologic surgeons. But why wait for definitive evidence to accrue?
“In light of these hazards – and according to governmental guidelines – dermatologic surgeons would be wise to adopt protective measures during surgical procedures,” Dr. de Golian said.
But they haven’t. She cited a national survey conducted several years ago by a colleague in which 79% of the 316 responding dermatologic surgeons indicated they use no smoke management whatsoever, neither masks nor a local exhaust evacuation system. Only 10% employed smoke management 25%-50% of the time during electrocautery, and a scant 11% of dermatologic surgeons did so at least 75% of the time (Dermatol Surg. 2014 Dec;40[12]:1373-7).
Given the far more substantial expense of installing an office smoke evacuation system, mask filtration becomes an attractive alternative. But the relative efficacy of the various types of masks in blocking fine and ultrafine particulate matter contained in electrocautery plumes hadn’t previously been systematically studied. This created the impetus for Dr. de Golian’s study.
The N95 masks were the clear winner, particularly when it came to filtering the ultrafine particles, which are of greatest concern because they remain suspended in air longer and penetrate deeper into the respiratory tract than larger particles. The N95 masks proved superior to procedural masks, which in turn were significantly more effective than the laser masks. The differences between mask performance for larger particle filtration were smaller, although the N95 remained number one. She noted that the study results probably underestimate the true filtration efficacy of N95 masks, since they form a tighter seal with the face in clinical practice than with the other two mask types.
Mask self-protection “is easily applicable in your own practice, and it meets NIOSH-recommended [National Institute for Occupational Safety and Health] standards for safety in the workplace,” the dermatologist noted.
In the next phase of her research, she plans to evaluate the optimal technology and techniques of smoke evacuation in the surgical suite. That’s an attractive method because it protects everyone in the room, not just the surgeon. And while the practitioner survey indicates this technology isn’t widely used by dermatologic surgeons on a routine basis at present, that could change, particularly in the current era in which patient-reported outcomes and satisfaction surveys have taken on added weight.
“Patients prefer not smelling their own tissue burning,” Dr. de Golian said.
She reported no financial conflicts regarding her study, which was conducted free of commercial support.
CHICAGO – Routine use of an N95 mask during electrocautery is an effective and inexpensive way for dermatologic surgeons to protect themselves from toxic, airborne particulate matter in the smoke generated during the procedure, Emily de Golian, MD, said at the annual meeting of the American College of Mohs Surgery.
“Our data suggest clear as well as superiority to the laser masks that are used in hair removal procedures and ablative procedures in cosmetic clinics,” commented Dr. de Golian, a Mohs micrographic surgery fellow at the University of California, San Diego.
This matter of self-protection from the effects of electrocautery smoke plumes deserves greater attention from the dermatologic community, according to Dr. de Golian. There is solid evidence that these plumes contain high concentrations of known carcinogens, including benzene, acetonitrile, and butadiene – indeed, concentrations far in excess of what’s found in second-hand cigarette smoke. Moreover, many of these airborne carcinogens and other toxins have been linked to leukemia, neurologic disorders, lung cancer, thrombotic disorders, lung disease, and infectious disease transmission, albeit not convincingly so to date in dermatologic surgeons. But why wait for definitive evidence to accrue?
“In light of these hazards – and according to governmental guidelines – dermatologic surgeons would be wise to adopt protective measures during surgical procedures,” Dr. de Golian said.
But they haven’t. She cited a national survey conducted several years ago by a colleague in which 79% of the 316 responding dermatologic surgeons indicated they use no smoke management whatsoever, neither masks nor a local exhaust evacuation system. Only 10% employed smoke management 25%-50% of the time during electrocautery, and a scant 11% of dermatologic surgeons did so at least 75% of the time (Dermatol Surg. 2014 Dec;40[12]:1373-7).
Given the far more substantial expense of installing an office smoke evacuation system, mask filtration becomes an attractive alternative. But the relative efficacy of the various types of masks in blocking fine and ultrafine particulate matter contained in electrocautery plumes hadn’t previously been systematically studied. This created the impetus for Dr. de Golian’s study.
The N95 masks were the clear winner, particularly when it came to filtering the ultrafine particles, which are of greatest concern because they remain suspended in air longer and penetrate deeper into the respiratory tract than larger particles. The N95 masks proved superior to procedural masks, which in turn were significantly more effective than the laser masks. The differences between mask performance for larger particle filtration were smaller, although the N95 remained number one. She noted that the study results probably underestimate the true filtration efficacy of N95 masks, since they form a tighter seal with the face in clinical practice than with the other two mask types.
Mask self-protection “is easily applicable in your own practice, and it meets NIOSH-recommended [National Institute for Occupational Safety and Health] standards for safety in the workplace,” the dermatologist noted.
In the next phase of her research, she plans to evaluate the optimal technology and techniques of smoke evacuation in the surgical suite. That’s an attractive method because it protects everyone in the room, not just the surgeon. And while the practitioner survey indicates this technology isn’t widely used by dermatologic surgeons on a routine basis at present, that could change, particularly in the current era in which patient-reported outcomes and satisfaction surveys have taken on added weight.
“Patients prefer not smelling their own tissue burning,” Dr. de Golian said.
She reported no financial conflicts regarding her study, which was conducted free of commercial support.
REPORTING FROM THE ACMS ANNUAL MEETING
Key clinical point: Electrocautery smoke is bad news, and wearing an N95 mask affords protection.
Major finding: The N95 mask was significantly more effective than basic procedural or laser masks at filtering particulate matter less than 1 mcm in size contained in electrocautery smoke.
Study details: This study utilized highly sensitive airborne particle counting devices to assess the relative protective filtration afforded by three types of masks.
Disclosures: The presenter reported no financial conflicts regarding this study, which was conducted free of commercial support.
Where the latest HCV drug combos fit in
MAUI, HAWAII – The addition of the two latest treatment regimens to receive approval for hepatitis C essentially closes the circle on treatment of this disease, Steven L. Flamm, MD, declared at the Gastroenterology Updates, IBD, Liver Disease meeting.
“We now have good options available for all the hepatitis C scenarios you will ever see in your practice,” said Dr. Flamm, professor of medicine and chief of the hepatology program at Northwestern University, Chicago.
Moreover, this wide range of highly effective, well-tolerated therapies is having a major clinical impact.
“We’re already seeing a decline in the number of patients who are listed for liver transplantation with hepatitis C as the indication with UNOS [the United Organ Sharing database],” the gastroenterologist noted, citing a study presented at the 2017 annual meeting of the American Association for the Study of Liver Disease that showed that the proportion of patients who join the transplant wait-list with hepatitis C as their qualifying diagnosis has fallen by 35% since approval of the direct-acting antiviral (DAA) regimens in late 2013.
What’s special about the two newest DAA treatment regimens – sofosbuvir/velpatasvir/voxilaprevir (Vosevi) and glecaprevir/pibrentasvir (Mavyret) – is that they are pangenotypic, they are effective in prior treatment failures, they don’t need to be accompanied by ribavirin, and there is no need for baseline pretreatment resistance-associated substitution testing, Dr. Flamm noted.
“So if you have a patient sitting in front of you with any genotype of hepatitis C infection who has failed on NS5a-inhibitor therapy, you can tell them in general their chance of getting an SVR [sustained viral response] with sofosbuvir/velpatasvir/voxilaprevir is about 97%. And you can give it without worrying about what resistances they might have to begin with,” he said.
His copanelist Norah Terrault, MD, agreed that these two regimens are important additions.
“Glecaprevir/pibrentasvir is the first pangenic 8-week regimen for noncirrhotics. This is a major advance. And now having sofosbuvir/velpatasvir/voxilaprevir for treatment-experienced patients, that’s another strong advance,” commented Dr. Terrault, professor of medicine and director of the Viral Hepatitis Center at the University of California, San Francisco.
Dr. Flamm said the biggest remaining challenge in the treatment of hepatitis C is to gain improved access to therapy.
“The public-aid patients make up 30%-35% of patients with hepatitis C in my part of the country, and they still can’t get therapy unless they have cirrhosis. We can’t even treat people who have stage 2 fibrosis if they’re public-aid patients in Illinois. So we can’t achieve the goal of eliminating hepatitis C,” Dr. Flamm said.
He reported having no financial conflicts regarding his presentation.
Encourage your patients to visit AGA’s new online GI Patient Center to learn more about digestive diseases, including HCV, at gastro.org/patient.
MAUI, HAWAII – The addition of the two latest treatment regimens to receive approval for hepatitis C essentially closes the circle on treatment of this disease, Steven L. Flamm, MD, declared at the Gastroenterology Updates, IBD, Liver Disease meeting.
“We now have good options available for all the hepatitis C scenarios you will ever see in your practice,” said Dr. Flamm, professor of medicine and chief of the hepatology program at Northwestern University, Chicago.
Moreover, this wide range of highly effective, well-tolerated therapies is having a major clinical impact.
“We’re already seeing a decline in the number of patients who are listed for liver transplantation with hepatitis C as the indication with UNOS [the United Organ Sharing database],” the gastroenterologist noted, citing a study presented at the 2017 annual meeting of the American Association for the Study of Liver Disease that showed that the proportion of patients who join the transplant wait-list with hepatitis C as their qualifying diagnosis has fallen by 35% since approval of the direct-acting antiviral (DAA) regimens in late 2013.
What’s special about the two newest DAA treatment regimens – sofosbuvir/velpatasvir/voxilaprevir (Vosevi) and glecaprevir/pibrentasvir (Mavyret) – is that they are pangenotypic, they are effective in prior treatment failures, they don’t need to be accompanied by ribavirin, and there is no need for baseline pretreatment resistance-associated substitution testing, Dr. Flamm noted.
“So if you have a patient sitting in front of you with any genotype of hepatitis C infection who has failed on NS5a-inhibitor therapy, you can tell them in general their chance of getting an SVR [sustained viral response] with sofosbuvir/velpatasvir/voxilaprevir is about 97%. And you can give it without worrying about what resistances they might have to begin with,” he said.
His copanelist Norah Terrault, MD, agreed that these two regimens are important additions.
“Glecaprevir/pibrentasvir is the first pangenic 8-week regimen for noncirrhotics. This is a major advance. And now having sofosbuvir/velpatasvir/voxilaprevir for treatment-experienced patients, that’s another strong advance,” commented Dr. Terrault, professor of medicine and director of the Viral Hepatitis Center at the University of California, San Francisco.
Dr. Flamm said the biggest remaining challenge in the treatment of hepatitis C is to gain improved access to therapy.
“The public-aid patients make up 30%-35% of patients with hepatitis C in my part of the country, and they still can’t get therapy unless they have cirrhosis. We can’t even treat people who have stage 2 fibrosis if they’re public-aid patients in Illinois. So we can’t achieve the goal of eliminating hepatitis C,” Dr. Flamm said.
He reported having no financial conflicts regarding his presentation.
Encourage your patients to visit AGA’s new online GI Patient Center to learn more about digestive diseases, including HCV, at gastro.org/patient.
MAUI, HAWAII – The addition of the two latest treatment regimens to receive approval for hepatitis C essentially closes the circle on treatment of this disease, Steven L. Flamm, MD, declared at the Gastroenterology Updates, IBD, Liver Disease meeting.
“We now have good options available for all the hepatitis C scenarios you will ever see in your practice,” said Dr. Flamm, professor of medicine and chief of the hepatology program at Northwestern University, Chicago.
Moreover, this wide range of highly effective, well-tolerated therapies is having a major clinical impact.
“We’re already seeing a decline in the number of patients who are listed for liver transplantation with hepatitis C as the indication with UNOS [the United Organ Sharing database],” the gastroenterologist noted, citing a study presented at the 2017 annual meeting of the American Association for the Study of Liver Disease that showed that the proportion of patients who join the transplant wait-list with hepatitis C as their qualifying diagnosis has fallen by 35% since approval of the direct-acting antiviral (DAA) regimens in late 2013.
What’s special about the two newest DAA treatment regimens – sofosbuvir/velpatasvir/voxilaprevir (Vosevi) and glecaprevir/pibrentasvir (Mavyret) – is that they are pangenotypic, they are effective in prior treatment failures, they don’t need to be accompanied by ribavirin, and there is no need for baseline pretreatment resistance-associated substitution testing, Dr. Flamm noted.
“So if you have a patient sitting in front of you with any genotype of hepatitis C infection who has failed on NS5a-inhibitor therapy, you can tell them in general their chance of getting an SVR [sustained viral response] with sofosbuvir/velpatasvir/voxilaprevir is about 97%. And you can give it without worrying about what resistances they might have to begin with,” he said.
His copanelist Norah Terrault, MD, agreed that these two regimens are important additions.
“Glecaprevir/pibrentasvir is the first pangenic 8-week regimen for noncirrhotics. This is a major advance. And now having sofosbuvir/velpatasvir/voxilaprevir for treatment-experienced patients, that’s another strong advance,” commented Dr. Terrault, professor of medicine and director of the Viral Hepatitis Center at the University of California, San Francisco.
Dr. Flamm said the biggest remaining challenge in the treatment of hepatitis C is to gain improved access to therapy.
“The public-aid patients make up 30%-35% of patients with hepatitis C in my part of the country, and they still can’t get therapy unless they have cirrhosis. We can’t even treat people who have stage 2 fibrosis if they’re public-aid patients in Illinois. So we can’t achieve the goal of eliminating hepatitis C,” Dr. Flamm said.
He reported having no financial conflicts regarding his presentation.
Encourage your patients to visit AGA’s new online GI Patient Center to learn more about digestive diseases, including HCV, at gastro.org/patient.
EXPERT ANALYSIS FROM GUILD 2018
Novel targeted cancer drugs cause fewer arrhythmias
ORLANDO – Not all oncology drugs are equal when it comes to their risk of treatment-induced cardiac arrhythmias.
Indeed, compared with anthracycline-based regimens, long the workhorse in treating many forms of cancer, the novel targeted agents – tyrosine kinase inhibitors, immune checkpoint inhibitors, and monoclonal antibodies – were 40% less likely to result in a new arrhythmia diagnosis within 6 months of treatment initiation, in a large, single-center retrospective study reported by Andrew Nickel at the annual meeting of the American College of Cardiology.
Overall, 14% of cancer patients developed a first-ever cardiac arrhythmia within the first 6 months after treatment began. In a Cox multivariate analysis, treatment with a targeted cancer agent was independently associated with a 40% lower risk of arrhythmia, compared with anthracycline-containing therapy. Of note, the incidence of new-onset atrial fibrillation was closely similar in the two groups.
Several patient factors emerged as independent predictors of increased risk of cancer treatment–induced arrhythmia in the multivariate analysis: male sex, with a 1.2-fold increased risk; baseline heart failure, with a 2.2-fold risk; and hypertension, which conferred a 1.6-fold increased risk. These are patient groups in which the novel targeted cancer treatments are a particularly attractive option from the standpoint of mitigating arrhythmia risk, provided their use would be appropriate, he observed.
Mr. Nickel reported having no financial conflicts regarding his study, which was conducted free of commercial support.
SOURCE: Nickel A et al. ACC 18. Abstract 900-06.
ORLANDO – Not all oncology drugs are equal when it comes to their risk of treatment-induced cardiac arrhythmias.
Indeed, compared with anthracycline-based regimens, long the workhorse in treating many forms of cancer, the novel targeted agents – tyrosine kinase inhibitors, immune checkpoint inhibitors, and monoclonal antibodies – were 40% less likely to result in a new arrhythmia diagnosis within 6 months of treatment initiation, in a large, single-center retrospective study reported by Andrew Nickel at the annual meeting of the American College of Cardiology.
Overall, 14% of cancer patients developed a first-ever cardiac arrhythmia within the first 6 months after treatment began. In a Cox multivariate analysis, treatment with a targeted cancer agent was independently associated with a 40% lower risk of arrhythmia, compared with anthracycline-containing therapy. Of note, the incidence of new-onset atrial fibrillation was closely similar in the two groups.
Several patient factors emerged as independent predictors of increased risk of cancer treatment–induced arrhythmia in the multivariate analysis: male sex, with a 1.2-fold increased risk; baseline heart failure, with a 2.2-fold risk; and hypertension, which conferred a 1.6-fold increased risk. These are patient groups in which the novel targeted cancer treatments are a particularly attractive option from the standpoint of mitigating arrhythmia risk, provided their use would be appropriate, he observed.
Mr. Nickel reported having no financial conflicts regarding his study, which was conducted free of commercial support.
SOURCE: Nickel A et al. ACC 18. Abstract 900-06.
ORLANDO – Not all oncology drugs are equal when it comes to their risk of treatment-induced cardiac arrhythmias.
Indeed, compared with anthracycline-based regimens, long the workhorse in treating many forms of cancer, the novel targeted agents – tyrosine kinase inhibitors, immune checkpoint inhibitors, and monoclonal antibodies – were 40% less likely to result in a new arrhythmia diagnosis within 6 months of treatment initiation, in a large, single-center retrospective study reported by Andrew Nickel at the annual meeting of the American College of Cardiology.
Overall, 14% of cancer patients developed a first-ever cardiac arrhythmia within the first 6 months after treatment began. In a Cox multivariate analysis, treatment with a targeted cancer agent was independently associated with a 40% lower risk of arrhythmia, compared with anthracycline-containing therapy. Of note, the incidence of new-onset atrial fibrillation was closely similar in the two groups.
Several patient factors emerged as independent predictors of increased risk of cancer treatment–induced arrhythmia in the multivariate analysis: male sex, with a 1.2-fold increased risk; baseline heart failure, with a 2.2-fold risk; and hypertension, which conferred a 1.6-fold increased risk. These are patient groups in which the novel targeted cancer treatments are a particularly attractive option from the standpoint of mitigating arrhythmia risk, provided their use would be appropriate, he observed.
Mr. Nickel reported having no financial conflicts regarding his study, which was conducted free of commercial support.
SOURCE: Nickel A et al. ACC 18. Abstract 900-06.
REPORTING FROM ACC 2018
Key clinical point: The novel targeted cancer therapies cause markedly fewer cardiac arrhythmias.
Major finding: Cancer patients treated with a tyrosine kinase inhibitor, immune checkpoint inhibitor, or another of the novel targeted therapies were 40% less likely than were those on anthracycline-based therapy to develop a treatment-induced cardiac arrhythmia up to 6 months after treatment initiation.
Study details: This was a retrospective single-center study including more than 5,000 cancer patients.
Disclosures: The presenter reported having no financial conflicts regarding his study, which was conducted free of commercial support.
Source: Nickel A et al. ACC 18, Abstract #900-06.
When and how to suspect asthma misdiagnosis
NEW ORLEANS – Kyle I. Happel, MD, said at the annual meeting of the American College of Physicians.
“Asthma is a disease whose symptoms are caused by variable airflow obstruction. It varies throughout the day, usually, and certainly by the week or by the month. I want you to think about the variability of a patient’s disease symptoms in forming your index of suspicion for this disease,” urged Dr. Happel, of the section of pulmonary, critical care, and allergy/immunology at Louisiana State University Medical Center in New Orleans.
These phenomena occur often. In a Canadian multicenter study of more than 700 patients with a history of physician-diagnosed asthma within the past 5 years, current asthma was ruled out in fully 33% of them on the basis of no deterioration of asthma symptoms, no evidence of reversible airway obstruction, and no bronchial hyperresponsiveness after all asthma drugs were tapered off (JAMA. 2017 Jan 17;317[3]:269-79).
Wheezing is the most specific symptom of asthma, although it is not, in fact, terribly specific. In descending order, the next most specific symptoms are breathlessness, chest tightness, and cough.
The top seven diseases that mimic asthma symptoms are chronic obstructive pulmonary disease, rhinosinusitis, heart failure with preserved or reduced ejection fraction, gastroesophageal reflux disease, angina, anxiety, and vocal cord dysfunction syndrome.
Strike two for an asthma diagnosis is a patient’s report that albuterol doesn’t improve the symptoms. That definitely raises questions about the diagnosis.
“Most asthmatics get symptomatic relief from their disease,” Dr. Happel observed.
And, if there is no indication in the patient’s chart that the asthma diagnosis was based upon demonstration of airflow obstruction on spirometry, the diagnosis is thrown further into doubt. In the recent Canadian study, patients who didn’t undergo pulmonary function testing (PFT) to establish airflow limitation at their time of diagnosis were significantly less likely to have current asthma.
“I would strongly suggest everyone with the diagnosis of asthma get spirometry with bronchodilator testing,” Dr. Happel said. “Good-quality PFTs are critical in forming a solid diagnosis of asthma.”
In a patient who has symptoms consistent with asthma, a 200-cc and 12% or more improvement in forced expiratory volume in 1 second (FEV1) in response to bronchodilator challenge is supportive of the diagnosis. However, absence of reversible airway obstruction doesn’t exclude the possibility of asthma.
In the setting of low to-moderate clinical suspicion of asthma plus no demonstrable obstruction on spirometry, Dr. Happel recommends moving on to bronchial hyperreactivity testing via a methacholine challenge.
“The beauty of a methacholine challenge is that is has a high negative predictive value to help exclude the diagnosis of asthma, particularly in people who are having symptoms suggestive of asthma,” Dr. Happel explained. “If it takes more than 8 mg/mL of methacholine to elicit a 20% or greater decrease in FEV1, it’s probably something else. It’s not a particularly specific test, though; you can get false positives from a methacholine challenge.”
NEW ORLEANS – Kyle I. Happel, MD, said at the annual meeting of the American College of Physicians.
“Asthma is a disease whose symptoms are caused by variable airflow obstruction. It varies throughout the day, usually, and certainly by the week or by the month. I want you to think about the variability of a patient’s disease symptoms in forming your index of suspicion for this disease,” urged Dr. Happel, of the section of pulmonary, critical care, and allergy/immunology at Louisiana State University Medical Center in New Orleans.
These phenomena occur often. In a Canadian multicenter study of more than 700 patients with a history of physician-diagnosed asthma within the past 5 years, current asthma was ruled out in fully 33% of them on the basis of no deterioration of asthma symptoms, no evidence of reversible airway obstruction, and no bronchial hyperresponsiveness after all asthma drugs were tapered off (JAMA. 2017 Jan 17;317[3]:269-79).
Wheezing is the most specific symptom of asthma, although it is not, in fact, terribly specific. In descending order, the next most specific symptoms are breathlessness, chest tightness, and cough.
The top seven diseases that mimic asthma symptoms are chronic obstructive pulmonary disease, rhinosinusitis, heart failure with preserved or reduced ejection fraction, gastroesophageal reflux disease, angina, anxiety, and vocal cord dysfunction syndrome.
Strike two for an asthma diagnosis is a patient’s report that albuterol doesn’t improve the symptoms. That definitely raises questions about the diagnosis.
“Most asthmatics get symptomatic relief from their disease,” Dr. Happel observed.
And, if there is no indication in the patient’s chart that the asthma diagnosis was based upon demonstration of airflow obstruction on spirometry, the diagnosis is thrown further into doubt. In the recent Canadian study, patients who didn’t undergo pulmonary function testing (PFT) to establish airflow limitation at their time of diagnosis were significantly less likely to have current asthma.
“I would strongly suggest everyone with the diagnosis of asthma get spirometry with bronchodilator testing,” Dr. Happel said. “Good-quality PFTs are critical in forming a solid diagnosis of asthma.”
In a patient who has symptoms consistent with asthma, a 200-cc and 12% or more improvement in forced expiratory volume in 1 second (FEV1) in response to bronchodilator challenge is supportive of the diagnosis. However, absence of reversible airway obstruction doesn’t exclude the possibility of asthma.
In the setting of low to-moderate clinical suspicion of asthma plus no demonstrable obstruction on spirometry, Dr. Happel recommends moving on to bronchial hyperreactivity testing via a methacholine challenge.
“The beauty of a methacholine challenge is that is has a high negative predictive value to help exclude the diagnosis of asthma, particularly in people who are having symptoms suggestive of asthma,” Dr. Happel explained. “If it takes more than 8 mg/mL of methacholine to elicit a 20% or greater decrease in FEV1, it’s probably something else. It’s not a particularly specific test, though; you can get false positives from a methacholine challenge.”
NEW ORLEANS – Kyle I. Happel, MD, said at the annual meeting of the American College of Physicians.
“Asthma is a disease whose symptoms are caused by variable airflow obstruction. It varies throughout the day, usually, and certainly by the week or by the month. I want you to think about the variability of a patient’s disease symptoms in forming your index of suspicion for this disease,” urged Dr. Happel, of the section of pulmonary, critical care, and allergy/immunology at Louisiana State University Medical Center in New Orleans.
These phenomena occur often. In a Canadian multicenter study of more than 700 patients with a history of physician-diagnosed asthma within the past 5 years, current asthma was ruled out in fully 33% of them on the basis of no deterioration of asthma symptoms, no evidence of reversible airway obstruction, and no bronchial hyperresponsiveness after all asthma drugs were tapered off (JAMA. 2017 Jan 17;317[3]:269-79).
Wheezing is the most specific symptom of asthma, although it is not, in fact, terribly specific. In descending order, the next most specific symptoms are breathlessness, chest tightness, and cough.
The top seven diseases that mimic asthma symptoms are chronic obstructive pulmonary disease, rhinosinusitis, heart failure with preserved or reduced ejection fraction, gastroesophageal reflux disease, angina, anxiety, and vocal cord dysfunction syndrome.
Strike two for an asthma diagnosis is a patient’s report that albuterol doesn’t improve the symptoms. That definitely raises questions about the diagnosis.
“Most asthmatics get symptomatic relief from their disease,” Dr. Happel observed.
And, if there is no indication in the patient’s chart that the asthma diagnosis was based upon demonstration of airflow obstruction on spirometry, the diagnosis is thrown further into doubt. In the recent Canadian study, patients who didn’t undergo pulmonary function testing (PFT) to establish airflow limitation at their time of diagnosis were significantly less likely to have current asthma.
“I would strongly suggest everyone with the diagnosis of asthma get spirometry with bronchodilator testing,” Dr. Happel said. “Good-quality PFTs are critical in forming a solid diagnosis of asthma.”
In a patient who has symptoms consistent with asthma, a 200-cc and 12% or more improvement in forced expiratory volume in 1 second (FEV1) in response to bronchodilator challenge is supportive of the diagnosis. However, absence of reversible airway obstruction doesn’t exclude the possibility of asthma.
In the setting of low to-moderate clinical suspicion of asthma plus no demonstrable obstruction on spirometry, Dr. Happel recommends moving on to bronchial hyperreactivity testing via a methacholine challenge.
“The beauty of a methacholine challenge is that is has a high negative predictive value to help exclude the diagnosis of asthma, particularly in people who are having symptoms suggestive of asthma,” Dr. Happel explained. “If it takes more than 8 mg/mL of methacholine to elicit a 20% or greater decrease in FEV1, it’s probably something else. It’s not a particularly specific test, though; you can get false positives from a methacholine challenge.”
REPORTING FROM ACP INTERNAL MEDICINE
Where the latest HCV drug combos fit in
MAUI, HAWAII – The addition of the two latest treatment regimens to receive approval for hepatitis C essentially closes the circle on treatment of this disease, Steven L. Flamm, MD, declared at the Gastroenterology Updates, IBD, Liver Disease meeting.
“We now have good options available for all the hepatitis C scenarios you will ever see in your practice,” said Dr. Flamm, professor of medicine and chief of the hepatology program at Northwestern University, Chicago.
“We’re already seeing a decline in the number of patients who are listed for liver transplantation with hepatitis C as the indication with UNOS [the United Organ Sharing database],” the gastroenterologist noted, citing a study presented at the 2017 annual meeting of the American Association for the Study of Liver Disease that showed that the proportion of patients who join the transplant wait-list with hepatitis C as their qualifying diagnosis has fallen by 35% since approval of the direct-acting antiviral (DAA) regimens in late 2013.
What’s special about the two newest DAA treatment regimens – sofosbuvir/velpatasvir/voxilaprevir (Vosevi) and glecaprevir/pibrentasvir (Mavyret) – is that they are pangenotypic, they are effective in prior treatment failures, they don’t need to be accompanied by ribavirin, and there is no need for baseline pretreatment resistance-associated substitution testing, Dr. Flamm noted.
“So if you have a patient sitting in front of you with any genotype of hepatitis C infection who has failed on NS5a-inhibitor therapy, you can tell them in general their chance of getting an SVR [sustained viral response] with sofosbuvir/velpatasvir/voxilaprevir is about 97%. And you can give it without worrying about what resistances they might have to begin with,” he said.
His copanelist Norah Terrault, MD, agreed that these two regimens are important additions.
“Glecaprevir/pibrentasvir is the first pangenic 8-week regimen for noncirrhotics. This is a major advance. And now having sofosbuvir/velpatasvir/voxilaprevir for treatment-experienced patients, that’s another strong advance,” commented Dr. Terrault, professor of medicine and director of the Viral Hepatitis Center at the University of California, San Francisco.
Dr. Flamm said the biggest remaining challenge in the treatment of hepatitis C is to gain improved access to therapy.
“The public-aid patients make up 30%-35% of patients with hepatitis C in my part of the country, and they still can’t get therapy unless they have cirrhosis. We can’t even treat people who have stage 2 fibrosis if they’re public-aid patients in Illinois. So we can’t achieve the goal of eliminating hepatitis C,” Dr. Flamm said.
He reported having no financial conflicts regarding his presentation.
MAUI, HAWAII – The addition of the two latest treatment regimens to receive approval for hepatitis C essentially closes the circle on treatment of this disease, Steven L. Flamm, MD, declared at the Gastroenterology Updates, IBD, Liver Disease meeting.
“We now have good options available for all the hepatitis C scenarios you will ever see in your practice,” said Dr. Flamm, professor of medicine and chief of the hepatology program at Northwestern University, Chicago.
“We’re already seeing a decline in the number of patients who are listed for liver transplantation with hepatitis C as the indication with UNOS [the United Organ Sharing database],” the gastroenterologist noted, citing a study presented at the 2017 annual meeting of the American Association for the Study of Liver Disease that showed that the proportion of patients who join the transplant wait-list with hepatitis C as their qualifying diagnosis has fallen by 35% since approval of the direct-acting antiviral (DAA) regimens in late 2013.
What’s special about the two newest DAA treatment regimens – sofosbuvir/velpatasvir/voxilaprevir (Vosevi) and glecaprevir/pibrentasvir (Mavyret) – is that they are pangenotypic, they are effective in prior treatment failures, they don’t need to be accompanied by ribavirin, and there is no need for baseline pretreatment resistance-associated substitution testing, Dr. Flamm noted.
“So if you have a patient sitting in front of you with any genotype of hepatitis C infection who has failed on NS5a-inhibitor therapy, you can tell them in general their chance of getting an SVR [sustained viral response] with sofosbuvir/velpatasvir/voxilaprevir is about 97%. And you can give it without worrying about what resistances they might have to begin with,” he said.
His copanelist Norah Terrault, MD, agreed that these two regimens are important additions.
“Glecaprevir/pibrentasvir is the first pangenic 8-week regimen for noncirrhotics. This is a major advance. And now having sofosbuvir/velpatasvir/voxilaprevir for treatment-experienced patients, that’s another strong advance,” commented Dr. Terrault, professor of medicine and director of the Viral Hepatitis Center at the University of California, San Francisco.
Dr. Flamm said the biggest remaining challenge in the treatment of hepatitis C is to gain improved access to therapy.
“The public-aid patients make up 30%-35% of patients with hepatitis C in my part of the country, and they still can’t get therapy unless they have cirrhosis. We can’t even treat people who have stage 2 fibrosis if they’re public-aid patients in Illinois. So we can’t achieve the goal of eliminating hepatitis C,” Dr. Flamm said.
He reported having no financial conflicts regarding his presentation.
MAUI, HAWAII – The addition of the two latest treatment regimens to receive approval for hepatitis C essentially closes the circle on treatment of this disease, Steven L. Flamm, MD, declared at the Gastroenterology Updates, IBD, Liver Disease meeting.
“We now have good options available for all the hepatitis C scenarios you will ever see in your practice,” said Dr. Flamm, professor of medicine and chief of the hepatology program at Northwestern University, Chicago.
“We’re already seeing a decline in the number of patients who are listed for liver transplantation with hepatitis C as the indication with UNOS [the United Organ Sharing database],” the gastroenterologist noted, citing a study presented at the 2017 annual meeting of the American Association for the Study of Liver Disease that showed that the proportion of patients who join the transplant wait-list with hepatitis C as their qualifying diagnosis has fallen by 35% since approval of the direct-acting antiviral (DAA) regimens in late 2013.
What’s special about the two newest DAA treatment regimens – sofosbuvir/velpatasvir/voxilaprevir (Vosevi) and glecaprevir/pibrentasvir (Mavyret) – is that they are pangenotypic, they are effective in prior treatment failures, they don’t need to be accompanied by ribavirin, and there is no need for baseline pretreatment resistance-associated substitution testing, Dr. Flamm noted.
“So if you have a patient sitting in front of you with any genotype of hepatitis C infection who has failed on NS5a-inhibitor therapy, you can tell them in general their chance of getting an SVR [sustained viral response] with sofosbuvir/velpatasvir/voxilaprevir is about 97%. And you can give it without worrying about what resistances they might have to begin with,” he said.
His copanelist Norah Terrault, MD, agreed that these two regimens are important additions.
“Glecaprevir/pibrentasvir is the first pangenic 8-week regimen for noncirrhotics. This is a major advance. And now having sofosbuvir/velpatasvir/voxilaprevir for treatment-experienced patients, that’s another strong advance,” commented Dr. Terrault, professor of medicine and director of the Viral Hepatitis Center at the University of California, San Francisco.
Dr. Flamm said the biggest remaining challenge in the treatment of hepatitis C is to gain improved access to therapy.
“The public-aid patients make up 30%-35% of patients with hepatitis C in my part of the country, and they still can’t get therapy unless they have cirrhosis. We can’t even treat people who have stage 2 fibrosis if they’re public-aid patients in Illinois. So we can’t achieve the goal of eliminating hepatitis C,” Dr. Flamm said.
He reported having no financial conflicts regarding his presentation.
Drug-coated balloons: The future of hemodialysis access?
CHICAGO – Drug-coated balloons show promise of being a long-sought major advance in the endovascular treatment of stenotic arteriovenous fistulae and grafts for hemodialysis access, Syed M. Hussain, MD, said at a symposium on vascular surgery sponsored by Northwestern University.
Something significantly better than today’s standard treatment options is needed, according to Dr. Hussain. Medicare pays out more than $50 billion annually for the treatment of patients with end-stage renal disease, and a hefty chunk of that money goes for oft-repeated procedures aimed at preserving the patency of the access sites.
“Primary patency rates leave much room for improvement,” observed Dr. Hussain, a vascular surgeon at the Christie Clinic in Champaign, Ill.
Indeed, the 50% primary patency rate at 6 months that was optimistically declared a “reasonable goal” in the 2006 Kidney Disease Outcomes Quality Initiative is actually far-fetched using the conventional tools.
“That 50% patency at 6 months would be a tall order to try to meet. Anybody in this room that does fistulography and angioplasty knows the numbers are actually a lot lower than 50%,” said Dr. Hussain.
Plain old balloon angioplasty, the standard first-line intervention for stenotic hemodialysis access sites, has a 6-month patency rate of about 30%. Bare metal stents push the rate up to about 39%. Covered stent grafts are the most effective of the conventional treatment modalities, with a 6-month patency of 51%-53%; however, they are widely considered too expensive for routine use.
Drug-coated balloons (DCBs) have been available for close to 3 years for treatment of lower extremity peripheral artery disease, where they have achieved considerable success. The Food and Drug Administration has approved three commercially available DCBs for this purpose: Bard’s Lutonix 035 AV, Medtronic’s IN.PACT Admiral, and most recently the Stellarex DCB.
In addition, the Lutonix DCB is approved for treatment of dysfunctional or stenotic arteriovenous (AV) fistulae on the strength of the positive results of the first prospective randomized multicenter trial of a DCB versus balloon angioplasty for AV access stenosis as reported at a conference in Leipzig, Germany, in 2017 and summarized by Dr. Hussain.
The pathophysiology of arterial atherosclerotic stenosis is very different from the stenosis that plagues AV access for dialysis. Arterial atherosclerotic stenosis is due to neointimal hyperplasia caused by inflammation and barotrauma secondary to angioplasty. In contrast, the neointimal hyperplasia in AV access stenosis is due to smooth muscle cell proliferation in response to nonphysiologic blood flow dynamics and shear forces between a high-pressure arterial system and the low-pressure venous system to which it has been connected, with resultant stenosis at the venous outflow anastomosis and often at the cephalic arch, Dr. Hussain explained.
Other contributors to the high rate of early stenosis in AV fistulae and grafts include traumatic balloon dilation, uremia, and repetitive traumatic needle insertion.
The breakthrough for DCBs as a potential game changer in dialysis access stenosis came with the discovery that venous smooth muscle cells are much more sensitive to paclitaxel and other antiproliferative drugs than are arterial smooth muscle cells. All three commercially available DCBs utilize paclitaxel as their active agent.
Multiple small single-center studies involving off-label use of the DCBs for dialysis access stenosis strongly suggested 6-month patency rates were higher than with balloon angioplasty. Then came the core lab-adjudicated Lutonix multicenter trial, in which 285 hemodialysis patients at 23 sites were randomized to the DCB or balloon angioplasty. Participants had to have a target lesion less than 10 cm long and had to undergo successful predilatation with high-pressure balloon angioplasty.
“The key thing to remember when we talk about dialysis grafts or fistulae is that we have to look at patency in periods of months. We can’t look at years because it’s pretty unusual to see a fistula stay open that long. So most of the time we’re trying to achieve extra months on these types of circuits,” noted Dr. Hussain.
That being said, the 8-month target lesion primary patency rate was 61.6% in the Lutonix DCB group, compared with 49.4% for percutaneous angioplasty, a statistically significant and clinically meaningful difference. Moreover, 66 interventions were required to maintain target lesion patency during that time frame in the DCB group, versus 94 in the angioplasty group; that translated to a 30% reduction in repeat interventions.
“This clearly has the potential to save a lot of money for the health care system,” he said.
The two forms of treatment were equally safe.
The expanded indication for the Lutonix DCB that resulted from this large randomized trial has triggered considerable research interest in DCBs for AV access stenosis around the world. Major ongoing randomized trials include the PAVE trial in the United Kingdom, the Spanish FISBOL trial, the APERTO trial in the Netherlands, and an Israeli randomized trial restricted to patients with cephalic arch stenosis.
Dr. Hussain is particularly excited about the ongoing 330-patient, prospective, multicenter, single-blinded clinical trial of the IN.PACT Admiral DCB versus plain balloon angioplasty. The Medtronic DCB employs a higher dosage of paclitaxel: 3.5 mcg/mm2, compared with 2.0 mcg/mm2 for the Lutonix DCB. Also, due to differences in the excipients used in the two DCBs, the paclitaxel from the IN.PACT device stays in the media of blood vessels for up to 180 days, compared with 60 days following drug delivery with the Lutonix balloon. Whether this longer period of close range antiproliferative activity will translate into a higher patency rate remains to be seen.
Dr. Hussain reported having no financial conflicts of interest regarding his presentation.
Costs associated with the management of patients with chronic kidney disease, particularly those with end-stage renal disease requiring hemodialysis, is a huge component of the Medicare budget. The maintenance of functional vascular access in these patients remains an ongoing challenge and reduction of costs related to access failure is critical to the continued funding of the program. Traditional methods of maintaining access patency such as balloon angioplasty and bare metal stents have poor long-term outcomes, and moderate improvement is seen with the use of covered stents.
Dr. Hussain reviews the current status of drug-coated balloons (DCB) in the endovascular treatment of dysfunctional hemodialysis fistulas and grafts. Safety and efficacy data from a prospective randomized multicenter trial comparing the Bard Lutonix DCB and plain old balloon angioplasty demonstrated a significant improvement in primary patency and a 30% reduction in repeat interventions with the DCB. This led to FDA approval for the Lutonix DCB in the treatment of dysfunctional or stenotic arteriovenous fistulas. Encouraged by these results, researchers conducting ongoing international randomized trials are attempting to clarify the potential expanded indications for DCB in access stenosis. Of particular interest is the ongoing 330-patient prospective, multicenter IN-PACT trial comparing Admiral DCB to balloon angioplasty in failing arteriovenous fistulas. Both the Admiral DCB and Lutonix DCB utilize paclitaxel as the antiproliferative agent. Dr. Hussain describes the increased sensitivity of venous smooth muscle cells to paclitaxel and other antiproliferative drugs when compared with arterial smooth muscle cells. This exciting finding may explain the improved outcomes in the treatment of dialysis access lesions where pathology frequently occurs at the venous anastomosis or in the venous conduit.
Although early results with the use of DCBs are promising, ongoing clinical trials and careful analysis of data and cost effectiveness are critical to optimize outcomes in treating dialysis access dysfunction. Dr. Hussain appropriately expresses cautious optimism regarding the future of hemodialysis access with this new tool available to interventionists treating these complex patients.
Larry A. Scher, MD, is a vascular surgeon at Montefiore Einstein Center for Heart and Vascular Care, New York, and an associate medical editor for Vascular Specialist.
Costs associated with the management of patients with chronic kidney disease, particularly those with end-stage renal disease requiring hemodialysis, is a huge component of the Medicare budget. The maintenance of functional vascular access in these patients remains an ongoing challenge and reduction of costs related to access failure is critical to the continued funding of the program. Traditional methods of maintaining access patency such as balloon angioplasty and bare metal stents have poor long-term outcomes, and moderate improvement is seen with the use of covered stents.
Dr. Hussain reviews the current status of drug-coated balloons (DCB) in the endovascular treatment of dysfunctional hemodialysis fistulas and grafts. Safety and efficacy data from a prospective randomized multicenter trial comparing the Bard Lutonix DCB and plain old balloon angioplasty demonstrated a significant improvement in primary patency and a 30% reduction in repeat interventions with the DCB. This led to FDA approval for the Lutonix DCB in the treatment of dysfunctional or stenotic arteriovenous fistulas. Encouraged by these results, researchers conducting ongoing international randomized trials are attempting to clarify the potential expanded indications for DCB in access stenosis. Of particular interest is the ongoing 330-patient prospective, multicenter IN-PACT trial comparing Admiral DCB to balloon angioplasty in failing arteriovenous fistulas. Both the Admiral DCB and Lutonix DCB utilize paclitaxel as the antiproliferative agent. Dr. Hussain describes the increased sensitivity of venous smooth muscle cells to paclitaxel and other antiproliferative drugs when compared with arterial smooth muscle cells. This exciting finding may explain the improved outcomes in the treatment of dialysis access lesions where pathology frequently occurs at the venous anastomosis or in the venous conduit.
Although early results with the use of DCBs are promising, ongoing clinical trials and careful analysis of data and cost effectiveness are critical to optimize outcomes in treating dialysis access dysfunction. Dr. Hussain appropriately expresses cautious optimism regarding the future of hemodialysis access with this new tool available to interventionists treating these complex patients.
Larry A. Scher, MD, is a vascular surgeon at Montefiore Einstein Center for Heart and Vascular Care, New York, and an associate medical editor for Vascular Specialist.
Costs associated with the management of patients with chronic kidney disease, particularly those with end-stage renal disease requiring hemodialysis, is a huge component of the Medicare budget. The maintenance of functional vascular access in these patients remains an ongoing challenge and reduction of costs related to access failure is critical to the continued funding of the program. Traditional methods of maintaining access patency such as balloon angioplasty and bare metal stents have poor long-term outcomes, and moderate improvement is seen with the use of covered stents.
Dr. Hussain reviews the current status of drug-coated balloons (DCB) in the endovascular treatment of dysfunctional hemodialysis fistulas and grafts. Safety and efficacy data from a prospective randomized multicenter trial comparing the Bard Lutonix DCB and plain old balloon angioplasty demonstrated a significant improvement in primary patency and a 30% reduction in repeat interventions with the DCB. This led to FDA approval for the Lutonix DCB in the treatment of dysfunctional or stenotic arteriovenous fistulas. Encouraged by these results, researchers conducting ongoing international randomized trials are attempting to clarify the potential expanded indications for DCB in access stenosis. Of particular interest is the ongoing 330-patient prospective, multicenter IN-PACT trial comparing Admiral DCB to balloon angioplasty in failing arteriovenous fistulas. Both the Admiral DCB and Lutonix DCB utilize paclitaxel as the antiproliferative agent. Dr. Hussain describes the increased sensitivity of venous smooth muscle cells to paclitaxel and other antiproliferative drugs when compared with arterial smooth muscle cells. This exciting finding may explain the improved outcomes in the treatment of dialysis access lesions where pathology frequently occurs at the venous anastomosis or in the venous conduit.
Although early results with the use of DCBs are promising, ongoing clinical trials and careful analysis of data and cost effectiveness are critical to optimize outcomes in treating dialysis access dysfunction. Dr. Hussain appropriately expresses cautious optimism regarding the future of hemodialysis access with this new tool available to interventionists treating these complex patients.
Larry A. Scher, MD, is a vascular surgeon at Montefiore Einstein Center for Heart and Vascular Care, New York, and an associate medical editor for Vascular Specialist.
CHICAGO – Drug-coated balloons show promise of being a long-sought major advance in the endovascular treatment of stenotic arteriovenous fistulae and grafts for hemodialysis access, Syed M. Hussain, MD, said at a symposium on vascular surgery sponsored by Northwestern University.
Something significantly better than today’s standard treatment options is needed, according to Dr. Hussain. Medicare pays out more than $50 billion annually for the treatment of patients with end-stage renal disease, and a hefty chunk of that money goes for oft-repeated procedures aimed at preserving the patency of the access sites.
“Primary patency rates leave much room for improvement,” observed Dr. Hussain, a vascular surgeon at the Christie Clinic in Champaign, Ill.
Indeed, the 50% primary patency rate at 6 months that was optimistically declared a “reasonable goal” in the 2006 Kidney Disease Outcomes Quality Initiative is actually far-fetched using the conventional tools.
“That 50% patency at 6 months would be a tall order to try to meet. Anybody in this room that does fistulography and angioplasty knows the numbers are actually a lot lower than 50%,” said Dr. Hussain.
Plain old balloon angioplasty, the standard first-line intervention for stenotic hemodialysis access sites, has a 6-month patency rate of about 30%. Bare metal stents push the rate up to about 39%. Covered stent grafts are the most effective of the conventional treatment modalities, with a 6-month patency of 51%-53%; however, they are widely considered too expensive for routine use.
Drug-coated balloons (DCBs) have been available for close to 3 years for treatment of lower extremity peripheral artery disease, where they have achieved considerable success. The Food and Drug Administration has approved three commercially available DCBs for this purpose: Bard’s Lutonix 035 AV, Medtronic’s IN.PACT Admiral, and most recently the Stellarex DCB.
In addition, the Lutonix DCB is approved for treatment of dysfunctional or stenotic arteriovenous (AV) fistulae on the strength of the positive results of the first prospective randomized multicenter trial of a DCB versus balloon angioplasty for AV access stenosis as reported at a conference in Leipzig, Germany, in 2017 and summarized by Dr. Hussain.
The pathophysiology of arterial atherosclerotic stenosis is very different from the stenosis that plagues AV access for dialysis. Arterial atherosclerotic stenosis is due to neointimal hyperplasia caused by inflammation and barotrauma secondary to angioplasty. In contrast, the neointimal hyperplasia in AV access stenosis is due to smooth muscle cell proliferation in response to nonphysiologic blood flow dynamics and shear forces between a high-pressure arterial system and the low-pressure venous system to which it has been connected, with resultant stenosis at the venous outflow anastomosis and often at the cephalic arch, Dr. Hussain explained.
Other contributors to the high rate of early stenosis in AV fistulae and grafts include traumatic balloon dilation, uremia, and repetitive traumatic needle insertion.
The breakthrough for DCBs as a potential game changer in dialysis access stenosis came with the discovery that venous smooth muscle cells are much more sensitive to paclitaxel and other antiproliferative drugs than are arterial smooth muscle cells. All three commercially available DCBs utilize paclitaxel as their active agent.
Multiple small single-center studies involving off-label use of the DCBs for dialysis access stenosis strongly suggested 6-month patency rates were higher than with balloon angioplasty. Then came the core lab-adjudicated Lutonix multicenter trial, in which 285 hemodialysis patients at 23 sites were randomized to the DCB or balloon angioplasty. Participants had to have a target lesion less than 10 cm long and had to undergo successful predilatation with high-pressure balloon angioplasty.
“The key thing to remember when we talk about dialysis grafts or fistulae is that we have to look at patency in periods of months. We can’t look at years because it’s pretty unusual to see a fistula stay open that long. So most of the time we’re trying to achieve extra months on these types of circuits,” noted Dr. Hussain.
That being said, the 8-month target lesion primary patency rate was 61.6% in the Lutonix DCB group, compared with 49.4% for percutaneous angioplasty, a statistically significant and clinically meaningful difference. Moreover, 66 interventions were required to maintain target lesion patency during that time frame in the DCB group, versus 94 in the angioplasty group; that translated to a 30% reduction in repeat interventions.
“This clearly has the potential to save a lot of money for the health care system,” he said.
The two forms of treatment were equally safe.
The expanded indication for the Lutonix DCB that resulted from this large randomized trial has triggered considerable research interest in DCBs for AV access stenosis around the world. Major ongoing randomized trials include the PAVE trial in the United Kingdom, the Spanish FISBOL trial, the APERTO trial in the Netherlands, and an Israeli randomized trial restricted to patients with cephalic arch stenosis.
Dr. Hussain is particularly excited about the ongoing 330-patient, prospective, multicenter, single-blinded clinical trial of the IN.PACT Admiral DCB versus plain balloon angioplasty. The Medtronic DCB employs a higher dosage of paclitaxel: 3.5 mcg/mm2, compared with 2.0 mcg/mm2 for the Lutonix DCB. Also, due to differences in the excipients used in the two DCBs, the paclitaxel from the IN.PACT device stays in the media of blood vessels for up to 180 days, compared with 60 days following drug delivery with the Lutonix balloon. Whether this longer period of close range antiproliferative activity will translate into a higher patency rate remains to be seen.
Dr. Hussain reported having no financial conflicts of interest regarding his presentation.
CHICAGO – Drug-coated balloons show promise of being a long-sought major advance in the endovascular treatment of stenotic arteriovenous fistulae and grafts for hemodialysis access, Syed M. Hussain, MD, said at a symposium on vascular surgery sponsored by Northwestern University.
Something significantly better than today’s standard treatment options is needed, according to Dr. Hussain. Medicare pays out more than $50 billion annually for the treatment of patients with end-stage renal disease, and a hefty chunk of that money goes for oft-repeated procedures aimed at preserving the patency of the access sites.
“Primary patency rates leave much room for improvement,” observed Dr. Hussain, a vascular surgeon at the Christie Clinic in Champaign, Ill.
Indeed, the 50% primary patency rate at 6 months that was optimistically declared a “reasonable goal” in the 2006 Kidney Disease Outcomes Quality Initiative is actually far-fetched using the conventional tools.
“That 50% patency at 6 months would be a tall order to try to meet. Anybody in this room that does fistulography and angioplasty knows the numbers are actually a lot lower than 50%,” said Dr. Hussain.
Plain old balloon angioplasty, the standard first-line intervention for stenotic hemodialysis access sites, has a 6-month patency rate of about 30%. Bare metal stents push the rate up to about 39%. Covered stent grafts are the most effective of the conventional treatment modalities, with a 6-month patency of 51%-53%; however, they are widely considered too expensive for routine use.
Drug-coated balloons (DCBs) have been available for close to 3 years for treatment of lower extremity peripheral artery disease, where they have achieved considerable success. The Food and Drug Administration has approved three commercially available DCBs for this purpose: Bard’s Lutonix 035 AV, Medtronic’s IN.PACT Admiral, and most recently the Stellarex DCB.
In addition, the Lutonix DCB is approved for treatment of dysfunctional or stenotic arteriovenous (AV) fistulae on the strength of the positive results of the first prospective randomized multicenter trial of a DCB versus balloon angioplasty for AV access stenosis as reported at a conference in Leipzig, Germany, in 2017 and summarized by Dr. Hussain.
The pathophysiology of arterial atherosclerotic stenosis is very different from the stenosis that plagues AV access for dialysis. Arterial atherosclerotic stenosis is due to neointimal hyperplasia caused by inflammation and barotrauma secondary to angioplasty. In contrast, the neointimal hyperplasia in AV access stenosis is due to smooth muscle cell proliferation in response to nonphysiologic blood flow dynamics and shear forces between a high-pressure arterial system and the low-pressure venous system to which it has been connected, with resultant stenosis at the venous outflow anastomosis and often at the cephalic arch, Dr. Hussain explained.
Other contributors to the high rate of early stenosis in AV fistulae and grafts include traumatic balloon dilation, uremia, and repetitive traumatic needle insertion.
The breakthrough for DCBs as a potential game changer in dialysis access stenosis came with the discovery that venous smooth muscle cells are much more sensitive to paclitaxel and other antiproliferative drugs than are arterial smooth muscle cells. All three commercially available DCBs utilize paclitaxel as their active agent.
Multiple small single-center studies involving off-label use of the DCBs for dialysis access stenosis strongly suggested 6-month patency rates were higher than with balloon angioplasty. Then came the core lab-adjudicated Lutonix multicenter trial, in which 285 hemodialysis patients at 23 sites were randomized to the DCB or balloon angioplasty. Participants had to have a target lesion less than 10 cm long and had to undergo successful predilatation with high-pressure balloon angioplasty.
“The key thing to remember when we talk about dialysis grafts or fistulae is that we have to look at patency in periods of months. We can’t look at years because it’s pretty unusual to see a fistula stay open that long. So most of the time we’re trying to achieve extra months on these types of circuits,” noted Dr. Hussain.
That being said, the 8-month target lesion primary patency rate was 61.6% in the Lutonix DCB group, compared with 49.4% for percutaneous angioplasty, a statistically significant and clinically meaningful difference. Moreover, 66 interventions were required to maintain target lesion patency during that time frame in the DCB group, versus 94 in the angioplasty group; that translated to a 30% reduction in repeat interventions.
“This clearly has the potential to save a lot of money for the health care system,” he said.
The two forms of treatment were equally safe.
The expanded indication for the Lutonix DCB that resulted from this large randomized trial has triggered considerable research interest in DCBs for AV access stenosis around the world. Major ongoing randomized trials include the PAVE trial in the United Kingdom, the Spanish FISBOL trial, the APERTO trial in the Netherlands, and an Israeli randomized trial restricted to patients with cephalic arch stenosis.
Dr. Hussain is particularly excited about the ongoing 330-patient, prospective, multicenter, single-blinded clinical trial of the IN.PACT Admiral DCB versus plain balloon angioplasty. The Medtronic DCB employs a higher dosage of paclitaxel: 3.5 mcg/mm2, compared with 2.0 mcg/mm2 for the Lutonix DCB. Also, due to differences in the excipients used in the two DCBs, the paclitaxel from the IN.PACT device stays in the media of blood vessels for up to 180 days, compared with 60 days following drug delivery with the Lutonix balloon. Whether this longer period of close range antiproliferative activity will translate into a higher patency rate remains to be seen.
Dr. Hussain reported having no financial conflicts of interest regarding his presentation.
EXPERT ANALYSIS FROM THE NORTHWESTERN VASCULAR SYMPOSIUM
Cost-effectiveness battle: FFR vs. iFR in DEFINE-FLAIR trial
ORLANDO – The use of an instantaneous wave-free ratio (iFR)–guided strategy to identify physiologically significant coronary stenoses that warrant revascularization proved substantially more cost effective than did a fractional flow reserve (FFR)–based strategy in a prespecified secondary analysis of the randomized DEFINE-FLAIR trial, Manesh R. Patel, MD, reported at the annual meeting of the American College of Cardiology.
The difference in total health care costs over the course of a year of follow-up was $896 per patient in favor of the instantaneous wave-free ratio (iFR) approach, said Dr. Patel, a professor of medicine, the chief of the division of cardiology, and the chief of the division of clinical pharmacology at Duke University in Durham, N.C.
DEFINE-FLAIR was a multicenter study in which 2,492 patients with coronary artery disease were randomized to undergo either iFR- or FFR-guided coronary revascularization. It had previously been established that decision making regarding coronary revascularization or deferral that was guided by FFR leads to better patient outcomes than decision making guided by angiography alone.
DEFINE-FLAIR showed that iFR provides clinical benefits similar to those of FFR. The 1-year primary endpoint, a composite of all-cause mortality, nonfatal MI, or unplanned revascularization, occurred in 6.8% of the iFR group and 7.0% of the FFR group, while the revascularization rate was significantly lower in the iFR group, by a margin of 47.5% to 53.4% (N Engl J Med. 2017 May 11;376(19):1824-34).
Dr. Patel presented a formal study of total health care costs and quality of life in the two study arms through 1 year of follow-up. The cost of coronary physiologic assessment by iFR was lower because, unlike FFR, iFR doesn’t use adenosine for vasodilation. Plus, median procedural time was 4.5 minutes shorter in the iFR group, resulting in lower costs for staff time. After investigators added up the costs of balloons, stents, laboratory testing, and a year’s worth of primary care visits, specialty consults, and unplanned revascularization procedures, the total cost per patient was $7,442.23 in 2017 U.S. dollars in the iFR group and $8,243.39 in the FFR group.
Session cochair Christopher Granger, MD, was favorably impressed.
“With equal clinical outcomes, the iFR – in not using adenosine and by identifying fewer patients needing referral for coronary artery bypass surgery or percutaneous coronary intervention – had a better cost effectiveness by about $900. That’s pretty good,” commented Dr. Granger, a professor of medicine at Duke University.
“At the moment, there is a longer track record for FFR data than iFR data for outcomes, but this is a fairly strong finding in a large population in a well-conducted study, and it shows very positive favorable economic results,” the cardiologist added. “There is no doubt that this [iFR] does have streamlined work flow, lower cost, and the same outcomes. So I think this is actually quite a positive effect.”
Dr. Patel, in acknowledging that there is a spirited ongoing debate among some interventional cardiologists as to which coronary physiology assessment tool should be used, declared, “We should stop arguing about which one to use and just use more of it, first and foremost.”
“I couldn’t agree more,” Dr. Granger said. “Coronary physiology for best decision making, whichever index you decide to choose, will lead to better outcomes and lower cost.”
Dr. Patel estimated that, worldwide, coronary physiology assessment is used in cardiac catheterization laboratories in fewer than 20% of patients. Achieving a substantial increase in that number is a matter of physician education perhaps coupled with payer requirements that interventional cardiologists must demonstrate evidence of ischemia before performing percutaneous coronary intervention on a given coronary lesion. Also, the American College of Cardiology/American Heart Association guidelines, which at present give a Class IIa recommendation for the use of FFR in patients with an intermediate stenosis, probably need to be revisited in light of DEFINE-FLAIR.
“One might argue that the recommendation could be a little stronger. And we have other proven technologies now besides FFR,” he observed.
Dr. Patel reported receiving research grants from Philips Volcano, sponsor of the DEFINE-FLAIR trial, as well as from AstraZeneca, Bayer, Janssen, ProCyrion, and the National Heart, Lung, and Blood Institute. He serves as a consultant to AstraZeneca, Bayer, Janssen, and Medscape.
SOURCE: Patel MR et al. ACC 18, Abstract 402-09.
ORLANDO – The use of an instantaneous wave-free ratio (iFR)–guided strategy to identify physiologically significant coronary stenoses that warrant revascularization proved substantially more cost effective than did a fractional flow reserve (FFR)–based strategy in a prespecified secondary analysis of the randomized DEFINE-FLAIR trial, Manesh R. Patel, MD, reported at the annual meeting of the American College of Cardiology.
The difference in total health care costs over the course of a year of follow-up was $896 per patient in favor of the instantaneous wave-free ratio (iFR) approach, said Dr. Patel, a professor of medicine, the chief of the division of cardiology, and the chief of the division of clinical pharmacology at Duke University in Durham, N.C.
DEFINE-FLAIR was a multicenter study in which 2,492 patients with coronary artery disease were randomized to undergo either iFR- or FFR-guided coronary revascularization. It had previously been established that decision making regarding coronary revascularization or deferral that was guided by FFR leads to better patient outcomes than decision making guided by angiography alone.
DEFINE-FLAIR showed that iFR provides clinical benefits similar to those of FFR. The 1-year primary endpoint, a composite of all-cause mortality, nonfatal MI, or unplanned revascularization, occurred in 6.8% of the iFR group and 7.0% of the FFR group, while the revascularization rate was significantly lower in the iFR group, by a margin of 47.5% to 53.4% (N Engl J Med. 2017 May 11;376(19):1824-34).
Dr. Patel presented a formal study of total health care costs and quality of life in the two study arms through 1 year of follow-up. The cost of coronary physiologic assessment by iFR was lower because, unlike FFR, iFR doesn’t use adenosine for vasodilation. Plus, median procedural time was 4.5 minutes shorter in the iFR group, resulting in lower costs for staff time. After investigators added up the costs of balloons, stents, laboratory testing, and a year’s worth of primary care visits, specialty consults, and unplanned revascularization procedures, the total cost per patient was $7,442.23 in 2017 U.S. dollars in the iFR group and $8,243.39 in the FFR group.
Session cochair Christopher Granger, MD, was favorably impressed.
“With equal clinical outcomes, the iFR – in not using adenosine and by identifying fewer patients needing referral for coronary artery bypass surgery or percutaneous coronary intervention – had a better cost effectiveness by about $900. That’s pretty good,” commented Dr. Granger, a professor of medicine at Duke University.
“At the moment, there is a longer track record for FFR data than iFR data for outcomes, but this is a fairly strong finding in a large population in a well-conducted study, and it shows very positive favorable economic results,” the cardiologist added. “There is no doubt that this [iFR] does have streamlined work flow, lower cost, and the same outcomes. So I think this is actually quite a positive effect.”
Dr. Patel, in acknowledging that there is a spirited ongoing debate among some interventional cardiologists as to which coronary physiology assessment tool should be used, declared, “We should stop arguing about which one to use and just use more of it, first and foremost.”
“I couldn’t agree more,” Dr. Granger said. “Coronary physiology for best decision making, whichever index you decide to choose, will lead to better outcomes and lower cost.”
Dr. Patel estimated that, worldwide, coronary physiology assessment is used in cardiac catheterization laboratories in fewer than 20% of patients. Achieving a substantial increase in that number is a matter of physician education perhaps coupled with payer requirements that interventional cardiologists must demonstrate evidence of ischemia before performing percutaneous coronary intervention on a given coronary lesion. Also, the American College of Cardiology/American Heart Association guidelines, which at present give a Class IIa recommendation for the use of FFR in patients with an intermediate stenosis, probably need to be revisited in light of DEFINE-FLAIR.
“One might argue that the recommendation could be a little stronger. And we have other proven technologies now besides FFR,” he observed.
Dr. Patel reported receiving research grants from Philips Volcano, sponsor of the DEFINE-FLAIR trial, as well as from AstraZeneca, Bayer, Janssen, ProCyrion, and the National Heart, Lung, and Blood Institute. He serves as a consultant to AstraZeneca, Bayer, Janssen, and Medscape.
SOURCE: Patel MR et al. ACC 18, Abstract 402-09.
ORLANDO – The use of an instantaneous wave-free ratio (iFR)–guided strategy to identify physiologically significant coronary stenoses that warrant revascularization proved substantially more cost effective than did a fractional flow reserve (FFR)–based strategy in a prespecified secondary analysis of the randomized DEFINE-FLAIR trial, Manesh R. Patel, MD, reported at the annual meeting of the American College of Cardiology.
The difference in total health care costs over the course of a year of follow-up was $896 per patient in favor of the instantaneous wave-free ratio (iFR) approach, said Dr. Patel, a professor of medicine, the chief of the division of cardiology, and the chief of the division of clinical pharmacology at Duke University in Durham, N.C.
DEFINE-FLAIR was a multicenter study in which 2,492 patients with coronary artery disease were randomized to undergo either iFR- or FFR-guided coronary revascularization. It had previously been established that decision making regarding coronary revascularization or deferral that was guided by FFR leads to better patient outcomes than decision making guided by angiography alone.
DEFINE-FLAIR showed that iFR provides clinical benefits similar to those of FFR. The 1-year primary endpoint, a composite of all-cause mortality, nonfatal MI, or unplanned revascularization, occurred in 6.8% of the iFR group and 7.0% of the FFR group, while the revascularization rate was significantly lower in the iFR group, by a margin of 47.5% to 53.4% (N Engl J Med. 2017 May 11;376(19):1824-34).
Dr. Patel presented a formal study of total health care costs and quality of life in the two study arms through 1 year of follow-up. The cost of coronary physiologic assessment by iFR was lower because, unlike FFR, iFR doesn’t use adenosine for vasodilation. Plus, median procedural time was 4.5 minutes shorter in the iFR group, resulting in lower costs for staff time. After investigators added up the costs of balloons, stents, laboratory testing, and a year’s worth of primary care visits, specialty consults, and unplanned revascularization procedures, the total cost per patient was $7,442.23 in 2017 U.S. dollars in the iFR group and $8,243.39 in the FFR group.
Session cochair Christopher Granger, MD, was favorably impressed.
“With equal clinical outcomes, the iFR – in not using adenosine and by identifying fewer patients needing referral for coronary artery bypass surgery or percutaneous coronary intervention – had a better cost effectiveness by about $900. That’s pretty good,” commented Dr. Granger, a professor of medicine at Duke University.
“At the moment, there is a longer track record for FFR data than iFR data for outcomes, but this is a fairly strong finding in a large population in a well-conducted study, and it shows very positive favorable economic results,” the cardiologist added. “There is no doubt that this [iFR] does have streamlined work flow, lower cost, and the same outcomes. So I think this is actually quite a positive effect.”
Dr. Patel, in acknowledging that there is a spirited ongoing debate among some interventional cardiologists as to which coronary physiology assessment tool should be used, declared, “We should stop arguing about which one to use and just use more of it, first and foremost.”
“I couldn’t agree more,” Dr. Granger said. “Coronary physiology for best decision making, whichever index you decide to choose, will lead to better outcomes and lower cost.”
Dr. Patel estimated that, worldwide, coronary physiology assessment is used in cardiac catheterization laboratories in fewer than 20% of patients. Achieving a substantial increase in that number is a matter of physician education perhaps coupled with payer requirements that interventional cardiologists must demonstrate evidence of ischemia before performing percutaneous coronary intervention on a given coronary lesion. Also, the American College of Cardiology/American Heart Association guidelines, which at present give a Class IIa recommendation for the use of FFR in patients with an intermediate stenosis, probably need to be revisited in light of DEFINE-FLAIR.
“One might argue that the recommendation could be a little stronger. And we have other proven technologies now besides FFR,” he observed.
Dr. Patel reported receiving research grants from Philips Volcano, sponsor of the DEFINE-FLAIR trial, as well as from AstraZeneca, Bayer, Janssen, ProCyrion, and the National Heart, Lung, and Blood Institute. He serves as a consultant to AstraZeneca, Bayer, Janssen, and Medscape.
SOURCE: Patel MR et al. ACC 18, Abstract 402-09.
REPORTING FROM ACC 2018
Key clinical point:
Major finding: A coronary revascularization strategy guided by physiologic information provided by instantaneous wave-free ratio resulted in $896 less in health care costs per patient over 1 year of follow-up than a fractional flow reserve–guided strategy had.
Study details: This was a prespecified analysis of all health care costs during 1 year of follow-up in the 2,492-patient randomized DEFINE-FLAIR study.
Disclosures: The study presenter reported receiving a research grant from Philips Volcano, sponsor of the DEFINE-FLAIR trial.
Source: Patel MR et al. ACC 18, Abstract 402-09.
Treatment of HCV in special populations
MAUI, HAWAII – Treatment of acute rather than chronic hepatitis C infection is well worth considering in selected circumstances, Norah Terrault, MD, asserted at the Gastroenterology Updates, IBD, Liver Disease meeting.
This is not at present guideline-recommended therapy. Current American Association for the Study of Liver Disease/Infectious Diseases Society of America guidance states that while there is emerging data to support treatment of acute hepatitis C, the evidence isn’t yet sufficiently robust to support a particular regimen or duration. The guidelines currently recommend waiting 6 months to see if the acute infection resolves spontaneously, as happens in a minority of cases, or becomes chronic, at which point it becomes guideline-directed treatment time. But Dr. Terrault believes persuasive evidence to back treatment of acute hepatitis C infection (HCV) is forthcoming, and she noted that the guidelines leave the door ajar by stating, “There are instances wherein a clinician may decide that the benefits of early treatment outweigh waiting for possible spontaneous clearance.”
Treatment of acute HCV
Dr. Terrault deems treatment of acute HCV warranted in circumstances in which there is significant danger of transmission from the acutely infected individual to others. For example, health care providers with a needlestick HCV infection, injecting drug users, and men with acute HCV/HIV coinfection. She also treats acute HCV in patients with underlying chronic liver disease.
“Clearly, I wouldn’t want those individuals to have any worsening of their liver function, so I would treat them acutely,” explained Dr. Terrault, professor of medicine and director of the Viral Hepatitis Center at the University of California, San Francisco.
She cited as particularly impressive the results of the SWIFT-C trial presented by Suzanna Naggie, MD, of Duke University, Durham, N.C., at the 2017 AASLD annual meeting. In this modest-size, National Institutes of Health–sponsored, multicenter study of HIV-infected men with acute HCV coinfection, the sustained viral response (SVR) rate with 8 weeks of ledipasvir/sofosbuvir (Harvoni) was 100%, regardless of their baseline HCV RNA level.
“I think this is remarkable. They cleared virus quite late and yet they went on to achieve HCV eradication. It highlights how little we really know about the treatment of individuals in this phase and that relying on HCV RNA levels may not tell the whole story. I think this is important data to suggest maybe when we treat acute hepatitis C we can use a shorter duration of treatment for that population. There are also other small studies testing 8 weeks of treatment in non–HIV-infected individuals with acute hepatitis C in which they also showed very high SVR rates,” the hepatologist said.
Copanelist Steven L. Flamm, MD, said that when he encounters a patient with acute HCV he, too, is prepared to offer treatment – he finds the available supporting evidence sufficiently compelling – but he often encounters a problem.
“Sometimes I’m blocked by insurance companies because this isn’t officially approved,” noted Dr. Flamm, professor of medicine and chief of the hepatology program at Northwestern University, Chicago.
“You’re right,” Dr. Terrault commented, “we have to make a pretty compelling argument to the insurer as to why we’re treating. But ‘treat to prevent transmission to others’ usually is successful in our hands.”
HCV in patients with end-stage renal disease
The product labeling for sofosbuvir (Sovaldi) says the drug’s safety and efficacy haven’t been established in patients with severe renal impairment or end-stage renal disease. However, a small multicenter study presented at the 2017 AASLD meeting demonstrated that 12 weeks of ledipasvir/sofosbuvir achieved a 100% SVR rate in patients with genotype 1 HCV and severe renal impairment, including some on dialysis, with no clinically meaningful change in estimated glomerular filtration rate or any signal of cardiac arrhythmia.
“The serum drug levels went up significantly, but reassuringly they saw no meaningful safety signals,” according to Dr. Terrault. “This, I think, is initial reassuring information that we were all very much waiting for.”
Still, as the AASLD/IDSA guidelines point out, ledipasvir/sofosbuvir is not a recommended option for HCV treatment in end-stage renal disease.
“In general, I think glecapravir/pibrentasvir [Mavyret] has become the go-to drug for patients who have renal dysfunction because it’s a pangenic regimen, it doesn’t require use of sofosbuvir, and there’s no dose adjustment. But I would say you could encounter situations where you might want to use sofosbuvir, and for me that situation is typically those direct-acting, antiviral-experienced patients who have failed other therapies and you really need to use sofosbuvir/velpatasvir/voxilaprevir [Vosevi] as your last or rescue therapy,” the hepatologist continued.
HCV in liver transplant recipients
“In the years before the direct-acting antivirals, treating transplant patients was always very challenging,” Dr. Terrault recalled. “They had very low response rates to therapy. That’s all gone away. Now we can say that liver transplant recipients who require treatment have response rates that are the same as in individuals who have not had a transplant. These patients are now being treated earlier and earlier after their transplant because you can do it safely.”
She pointed to a study presented at the 2017 AASLD meeting by Kosh Agarwal, MD, of Kings College London. It involved 79 adults with recurrent genotypes 1-4 HCV infection post–liver transplant who were treated with sofosbuvir/velpatasvir (Epclusa) for 12 weeks with a total SVR rate of 96%.
“The nice thing about sofosbuvir/velpatasvir is there are no drug-drug interactions with immunosuppressive drugs. Now it’s very easy to take care of these patients. The SVR rates are excellent,” Dr. Terrault observed.
The other combination that’s been studied specifically in liver transplant recipients, and in kidney transplant recipients as well, is glecapravir/pibrentasvir. In the MAGELLAN-2 study of 100 such patients with genotypes 1-6 HCV, the SVR rate was 99% with no drug-related adverse events leading to discontinuation.
Persons who inject drugs
The Centers for Disease Control and Prevention and the World Health Organization want HCV eradicated by 2030. If that’s going to happen, physicians will have to become more comfortable treating the disease in injectable drug users, a population with a high prevalence of HCV. Several studies have now shown that very high SVR rates can be achieved with direct-acting antiviral regimens as short as 8 weeks in these individuals, even if they are concurrently injecting drugs.
“There is increasing evidence that we should be doing more treatment in persons who inject drugs. Many of these individuals have very early disease and their response rates are excellent,” according to Dr. Terrault.
Moreover, their reinfection rates “are not outrageous,” she said: 1% or less in individuals who stopped injecting drugs decades prior to anti-HCV treatment, 5%-10% over the course of 3-5 years in those who continue injecting drugs after achieving SVR, and about 2% in those on methadone substitution therapy.
“These are very acceptable levels of reinfection if our goal is to move toward elimination of hepatitis C in this population,” she said.
She reported having no financial conflicts regarding her presentation.
MAUI, HAWAII – Treatment of acute rather than chronic hepatitis C infection is well worth considering in selected circumstances, Norah Terrault, MD, asserted at the Gastroenterology Updates, IBD, Liver Disease meeting.
This is not at present guideline-recommended therapy. Current American Association for the Study of Liver Disease/Infectious Diseases Society of America guidance states that while there is emerging data to support treatment of acute hepatitis C, the evidence isn’t yet sufficiently robust to support a particular regimen or duration. The guidelines currently recommend waiting 6 months to see if the acute infection resolves spontaneously, as happens in a minority of cases, or becomes chronic, at which point it becomes guideline-directed treatment time. But Dr. Terrault believes persuasive evidence to back treatment of acute hepatitis C infection (HCV) is forthcoming, and she noted that the guidelines leave the door ajar by stating, “There are instances wherein a clinician may decide that the benefits of early treatment outweigh waiting for possible spontaneous clearance.”
Treatment of acute HCV
Dr. Terrault deems treatment of acute HCV warranted in circumstances in which there is significant danger of transmission from the acutely infected individual to others. For example, health care providers with a needlestick HCV infection, injecting drug users, and men with acute HCV/HIV coinfection. She also treats acute HCV in patients with underlying chronic liver disease.
“Clearly, I wouldn’t want those individuals to have any worsening of their liver function, so I would treat them acutely,” explained Dr. Terrault, professor of medicine and director of the Viral Hepatitis Center at the University of California, San Francisco.
She cited as particularly impressive the results of the SWIFT-C trial presented by Suzanna Naggie, MD, of Duke University, Durham, N.C., at the 2017 AASLD annual meeting. In this modest-size, National Institutes of Health–sponsored, multicenter study of HIV-infected men with acute HCV coinfection, the sustained viral response (SVR) rate with 8 weeks of ledipasvir/sofosbuvir (Harvoni) was 100%, regardless of their baseline HCV RNA level.
“I think this is remarkable. They cleared virus quite late and yet they went on to achieve HCV eradication. It highlights how little we really know about the treatment of individuals in this phase and that relying on HCV RNA levels may not tell the whole story. I think this is important data to suggest maybe when we treat acute hepatitis C we can use a shorter duration of treatment for that population. There are also other small studies testing 8 weeks of treatment in non–HIV-infected individuals with acute hepatitis C in which they also showed very high SVR rates,” the hepatologist said.
Copanelist Steven L. Flamm, MD, said that when he encounters a patient with acute HCV he, too, is prepared to offer treatment – he finds the available supporting evidence sufficiently compelling – but he often encounters a problem.
“Sometimes I’m blocked by insurance companies because this isn’t officially approved,” noted Dr. Flamm, professor of medicine and chief of the hepatology program at Northwestern University, Chicago.
“You’re right,” Dr. Terrault commented, “we have to make a pretty compelling argument to the insurer as to why we’re treating. But ‘treat to prevent transmission to others’ usually is successful in our hands.”
HCV in patients with end-stage renal disease
The product labeling for sofosbuvir (Sovaldi) says the drug’s safety and efficacy haven’t been established in patients with severe renal impairment or end-stage renal disease. However, a small multicenter study presented at the 2017 AASLD meeting demonstrated that 12 weeks of ledipasvir/sofosbuvir achieved a 100% SVR rate in patients with genotype 1 HCV and severe renal impairment, including some on dialysis, with no clinically meaningful change in estimated glomerular filtration rate or any signal of cardiac arrhythmia.
“The serum drug levels went up significantly, but reassuringly they saw no meaningful safety signals,” according to Dr. Terrault. “This, I think, is initial reassuring information that we were all very much waiting for.”
Still, as the AASLD/IDSA guidelines point out, ledipasvir/sofosbuvir is not a recommended option for HCV treatment in end-stage renal disease.
“In general, I think glecapravir/pibrentasvir [Mavyret] has become the go-to drug for patients who have renal dysfunction because it’s a pangenic regimen, it doesn’t require use of sofosbuvir, and there’s no dose adjustment. But I would say you could encounter situations where you might want to use sofosbuvir, and for me that situation is typically those direct-acting, antiviral-experienced patients who have failed other therapies and you really need to use sofosbuvir/velpatasvir/voxilaprevir [Vosevi] as your last or rescue therapy,” the hepatologist continued.
HCV in liver transplant recipients
“In the years before the direct-acting antivirals, treating transplant patients was always very challenging,” Dr. Terrault recalled. “They had very low response rates to therapy. That’s all gone away. Now we can say that liver transplant recipients who require treatment have response rates that are the same as in individuals who have not had a transplant. These patients are now being treated earlier and earlier after their transplant because you can do it safely.”
She pointed to a study presented at the 2017 AASLD meeting by Kosh Agarwal, MD, of Kings College London. It involved 79 adults with recurrent genotypes 1-4 HCV infection post–liver transplant who were treated with sofosbuvir/velpatasvir (Epclusa) for 12 weeks with a total SVR rate of 96%.
“The nice thing about sofosbuvir/velpatasvir is there are no drug-drug interactions with immunosuppressive drugs. Now it’s very easy to take care of these patients. The SVR rates are excellent,” Dr. Terrault observed.
The other combination that’s been studied specifically in liver transplant recipients, and in kidney transplant recipients as well, is glecapravir/pibrentasvir. In the MAGELLAN-2 study of 100 such patients with genotypes 1-6 HCV, the SVR rate was 99% with no drug-related adverse events leading to discontinuation.
Persons who inject drugs
The Centers for Disease Control and Prevention and the World Health Organization want HCV eradicated by 2030. If that’s going to happen, physicians will have to become more comfortable treating the disease in injectable drug users, a population with a high prevalence of HCV. Several studies have now shown that very high SVR rates can be achieved with direct-acting antiviral regimens as short as 8 weeks in these individuals, even if they are concurrently injecting drugs.
“There is increasing evidence that we should be doing more treatment in persons who inject drugs. Many of these individuals have very early disease and their response rates are excellent,” according to Dr. Terrault.
Moreover, their reinfection rates “are not outrageous,” she said: 1% or less in individuals who stopped injecting drugs decades prior to anti-HCV treatment, 5%-10% over the course of 3-5 years in those who continue injecting drugs after achieving SVR, and about 2% in those on methadone substitution therapy.
“These are very acceptable levels of reinfection if our goal is to move toward elimination of hepatitis C in this population,” she said.
She reported having no financial conflicts regarding her presentation.
MAUI, HAWAII – Treatment of acute rather than chronic hepatitis C infection is well worth considering in selected circumstances, Norah Terrault, MD, asserted at the Gastroenterology Updates, IBD, Liver Disease meeting.
This is not at present guideline-recommended therapy. Current American Association for the Study of Liver Disease/Infectious Diseases Society of America guidance states that while there is emerging data to support treatment of acute hepatitis C, the evidence isn’t yet sufficiently robust to support a particular regimen or duration. The guidelines currently recommend waiting 6 months to see if the acute infection resolves spontaneously, as happens in a minority of cases, or becomes chronic, at which point it becomes guideline-directed treatment time. But Dr. Terrault believes persuasive evidence to back treatment of acute hepatitis C infection (HCV) is forthcoming, and she noted that the guidelines leave the door ajar by stating, “There are instances wherein a clinician may decide that the benefits of early treatment outweigh waiting for possible spontaneous clearance.”
Treatment of acute HCV
Dr. Terrault deems treatment of acute HCV warranted in circumstances in which there is significant danger of transmission from the acutely infected individual to others. For example, health care providers with a needlestick HCV infection, injecting drug users, and men with acute HCV/HIV coinfection. She also treats acute HCV in patients with underlying chronic liver disease.
“Clearly, I wouldn’t want those individuals to have any worsening of their liver function, so I would treat them acutely,” explained Dr. Terrault, professor of medicine and director of the Viral Hepatitis Center at the University of California, San Francisco.
She cited as particularly impressive the results of the SWIFT-C trial presented by Suzanna Naggie, MD, of Duke University, Durham, N.C., at the 2017 AASLD annual meeting. In this modest-size, National Institutes of Health–sponsored, multicenter study of HIV-infected men with acute HCV coinfection, the sustained viral response (SVR) rate with 8 weeks of ledipasvir/sofosbuvir (Harvoni) was 100%, regardless of their baseline HCV RNA level.
“I think this is remarkable. They cleared virus quite late and yet they went on to achieve HCV eradication. It highlights how little we really know about the treatment of individuals in this phase and that relying on HCV RNA levels may not tell the whole story. I think this is important data to suggest maybe when we treat acute hepatitis C we can use a shorter duration of treatment for that population. There are also other small studies testing 8 weeks of treatment in non–HIV-infected individuals with acute hepatitis C in which they also showed very high SVR rates,” the hepatologist said.
Copanelist Steven L. Flamm, MD, said that when he encounters a patient with acute HCV he, too, is prepared to offer treatment – he finds the available supporting evidence sufficiently compelling – but he often encounters a problem.
“Sometimes I’m blocked by insurance companies because this isn’t officially approved,” noted Dr. Flamm, professor of medicine and chief of the hepatology program at Northwestern University, Chicago.
“You’re right,” Dr. Terrault commented, “we have to make a pretty compelling argument to the insurer as to why we’re treating. But ‘treat to prevent transmission to others’ usually is successful in our hands.”
HCV in patients with end-stage renal disease
The product labeling for sofosbuvir (Sovaldi) says the drug’s safety and efficacy haven’t been established in patients with severe renal impairment or end-stage renal disease. However, a small multicenter study presented at the 2017 AASLD meeting demonstrated that 12 weeks of ledipasvir/sofosbuvir achieved a 100% SVR rate in patients with genotype 1 HCV and severe renal impairment, including some on dialysis, with no clinically meaningful change in estimated glomerular filtration rate or any signal of cardiac arrhythmia.
“The serum drug levels went up significantly, but reassuringly they saw no meaningful safety signals,” according to Dr. Terrault. “This, I think, is initial reassuring information that we were all very much waiting for.”
Still, as the AASLD/IDSA guidelines point out, ledipasvir/sofosbuvir is not a recommended option for HCV treatment in end-stage renal disease.
“In general, I think glecapravir/pibrentasvir [Mavyret] has become the go-to drug for patients who have renal dysfunction because it’s a pangenic regimen, it doesn’t require use of sofosbuvir, and there’s no dose adjustment. But I would say you could encounter situations where you might want to use sofosbuvir, and for me that situation is typically those direct-acting, antiviral-experienced patients who have failed other therapies and you really need to use sofosbuvir/velpatasvir/voxilaprevir [Vosevi] as your last or rescue therapy,” the hepatologist continued.
HCV in liver transplant recipients
“In the years before the direct-acting antivirals, treating transplant patients was always very challenging,” Dr. Terrault recalled. “They had very low response rates to therapy. That’s all gone away. Now we can say that liver transplant recipients who require treatment have response rates that are the same as in individuals who have not had a transplant. These patients are now being treated earlier and earlier after their transplant because you can do it safely.”
She pointed to a study presented at the 2017 AASLD meeting by Kosh Agarwal, MD, of Kings College London. It involved 79 adults with recurrent genotypes 1-4 HCV infection post–liver transplant who were treated with sofosbuvir/velpatasvir (Epclusa) for 12 weeks with a total SVR rate of 96%.
“The nice thing about sofosbuvir/velpatasvir is there are no drug-drug interactions with immunosuppressive drugs. Now it’s very easy to take care of these patients. The SVR rates are excellent,” Dr. Terrault observed.
The other combination that’s been studied specifically in liver transplant recipients, and in kidney transplant recipients as well, is glecapravir/pibrentasvir. In the MAGELLAN-2 study of 100 such patients with genotypes 1-6 HCV, the SVR rate was 99% with no drug-related adverse events leading to discontinuation.
Persons who inject drugs
The Centers for Disease Control and Prevention and the World Health Organization want HCV eradicated by 2030. If that’s going to happen, physicians will have to become more comfortable treating the disease in injectable drug users, a population with a high prevalence of HCV. Several studies have now shown that very high SVR rates can be achieved with direct-acting antiviral regimens as short as 8 weeks in these individuals, even if they are concurrently injecting drugs.
“There is increasing evidence that we should be doing more treatment in persons who inject drugs. Many of these individuals have very early disease and their response rates are excellent,” according to Dr. Terrault.
Moreover, their reinfection rates “are not outrageous,” she said: 1% or less in individuals who stopped injecting drugs decades prior to anti-HCV treatment, 5%-10% over the course of 3-5 years in those who continue injecting drugs after achieving SVR, and about 2% in those on methadone substitution therapy.
“These are very acceptable levels of reinfection if our goal is to move toward elimination of hepatitis C in this population,” she said.
She reported having no financial conflicts regarding her presentation.
EXPERT ANALYSIS FROM GUILD 2018
Nebivolol looks like best beta-blocker for hypertension
ORLANDO – The use of nebivolol as part of a multidrug regimen to treat hypertension was associated with a significantly lower cardiovascular event risk than was combination antihypertensive therapy featuring either metoprolol or atenolol in a large observational study, Brent M. Egan, MD, reported at the annual meeting of the American College of Cardiology.
The primary outcome was hospitalization for acute MI, stroke, heart failure, or angina during a mean 600 days of follow-up. In a Cox proportional hazards regression analysis, the risk of the composite outcome was 1.33-fold greater with atenolol and 1.91-fold greater with metoprolol than in the group on nebivolol for their hypertension.
The risk of hospitalization for MI was 1.47-fold greater in the atenolol group and 2.19-fold greater with metoprolol than in patients on nebivolol. Hospitalization for angina was 2.18 times more likely in the atenolol group and 3.39 times more likely in the metoprolol group than in patients on nebivolol. However, there was no between-group difference between the three beta-blockers in terms of stroke or heart failure rates, according to Dr. Egan of the University of South Carolina, Greenville.
He explained that the impetus for this study was that, even though beta-blockers are universally recognized as a cornerstone of secondary cardiovascular prevention, there are much fewer outcome data to support their use in primary prevention. Since nebivolol is a vasodilatory beta-blocker and atenolol and metoprolol are not, Dr. Egan and his coinvestigators hypothesized that this distinction could result in differences in cardiovascular event rates.
One audience member commented, “this study gives a nice hypothesis-generating rationale for doing a large randomized outcomes trial.” Dr. Egan concurred.
His study was supported by Allergan. He reported receiving research grants from Boehringer Ingelheim and serving as a consultant to Medtronic.
SOURCE: Egan BM et al. ACC 18, Abstract 1324M-11.
ORLANDO – The use of nebivolol as part of a multidrug regimen to treat hypertension was associated with a significantly lower cardiovascular event risk than was combination antihypertensive therapy featuring either metoprolol or atenolol in a large observational study, Brent M. Egan, MD, reported at the annual meeting of the American College of Cardiology.
The primary outcome was hospitalization for acute MI, stroke, heart failure, or angina during a mean 600 days of follow-up. In a Cox proportional hazards regression analysis, the risk of the composite outcome was 1.33-fold greater with atenolol and 1.91-fold greater with metoprolol than in the group on nebivolol for their hypertension.
The risk of hospitalization for MI was 1.47-fold greater in the atenolol group and 2.19-fold greater with metoprolol than in patients on nebivolol. Hospitalization for angina was 2.18 times more likely in the atenolol group and 3.39 times more likely in the metoprolol group than in patients on nebivolol. However, there was no between-group difference between the three beta-blockers in terms of stroke or heart failure rates, according to Dr. Egan of the University of South Carolina, Greenville.
He explained that the impetus for this study was that, even though beta-blockers are universally recognized as a cornerstone of secondary cardiovascular prevention, there are much fewer outcome data to support their use in primary prevention. Since nebivolol is a vasodilatory beta-blocker and atenolol and metoprolol are not, Dr. Egan and his coinvestigators hypothesized that this distinction could result in differences in cardiovascular event rates.
One audience member commented, “this study gives a nice hypothesis-generating rationale for doing a large randomized outcomes trial.” Dr. Egan concurred.
His study was supported by Allergan. He reported receiving research grants from Boehringer Ingelheim and serving as a consultant to Medtronic.
SOURCE: Egan BM et al. ACC 18, Abstract 1324M-11.
ORLANDO – The use of nebivolol as part of a multidrug regimen to treat hypertension was associated with a significantly lower cardiovascular event risk than was combination antihypertensive therapy featuring either metoprolol or atenolol in a large observational study, Brent M. Egan, MD, reported at the annual meeting of the American College of Cardiology.
The primary outcome was hospitalization for acute MI, stroke, heart failure, or angina during a mean 600 days of follow-up. In a Cox proportional hazards regression analysis, the risk of the composite outcome was 1.33-fold greater with atenolol and 1.91-fold greater with metoprolol than in the group on nebivolol for their hypertension.
The risk of hospitalization for MI was 1.47-fold greater in the atenolol group and 2.19-fold greater with metoprolol than in patients on nebivolol. Hospitalization for angina was 2.18 times more likely in the atenolol group and 3.39 times more likely in the metoprolol group than in patients on nebivolol. However, there was no between-group difference between the three beta-blockers in terms of stroke or heart failure rates, according to Dr. Egan of the University of South Carolina, Greenville.
He explained that the impetus for this study was that, even though beta-blockers are universally recognized as a cornerstone of secondary cardiovascular prevention, there are much fewer outcome data to support their use in primary prevention. Since nebivolol is a vasodilatory beta-blocker and atenolol and metoprolol are not, Dr. Egan and his coinvestigators hypothesized that this distinction could result in differences in cardiovascular event rates.
One audience member commented, “this study gives a nice hypothesis-generating rationale for doing a large randomized outcomes trial.” Dr. Egan concurred.
His study was supported by Allergan. He reported receiving research grants from Boehringer Ingelheim and serving as a consultant to Medtronic.
SOURCE: Egan BM et al. ACC 18, Abstract 1324M-11.
REPORTING FROM ACC 2018
Key clinical point:
Major finding: The risk of hospitalization for MI was 1.47-fold greater in patients on atenolol and 2.19-fold greater with metoprolol than in patients on nebivolol as part of a multidrug regimen to treat hypertension.
Study details: This retrospective observational study included three closely propensity score–matched groups, each 16,787 patients in size, on either nebivolol, metoprolol, or atenolol as part of a multidrug antihypertensive regimen.
Disclosures: The study was supported by Allergan. The presenter reported receiving research grants from Boehringer Ingelheim and serving as a consultant to Medtronic.
Source: Egan BM. ACC 2018, Abstract 1324M-11.