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Crizotinib Changes Practice for Advanced ALK-Positive NSCLC
VIENNA – Long-awaited data from the phase III PROFILE 1007 confirm that crizotinib provides superior progression-free survival and responses, compared with second-line chemotherapy in advanced anaplastic lymphoma kinase–positive non–small cell lung cancer.
Median progression-free survival more than doubled from 3.0 months with single-agent chemotherapy to 7.7 months with crizotinib, according to an independent radiologic review (P value less than .0001; hazard ratio, 0.49).
Crizotinib (Xalkori) remained superior regardless of whether chemotherapy contained docetaxel (Taxotere) (7.7 vs. 2.6 months; P less than .0001) or pemetrexed (Alimta) (7.7 vs. 4.2; P = .0004), an agent previously shown to be effective against ALK-positive NSCLC.
The overall response rate was 65.3% for crizotinib and 19.5% for chemotherapy in the intent to treat population of 347 patients (overall response rate ratio 3.4; P less than .0001).
Crizotinib was also associated with significantly greater improvement in lung cancer symptoms and quality of life, Dr. Alice Shaw reported during a presidential symposium at the joint congress of the European Cancer Organization, the European Society for Medical Oncology, and the European Society for Radiotherapy and Oncology.
"Taken together, these results establish crizotinib as the standard of care for patients with advanced, previously treated ALK-positive non–small cell lung cancer," she said.
ALK rearrangements are present in about 5% of lung cancers, typically in younger, never smokers.
Overall survival in the study was 22.8 months for chemotherapy and 20.3 months for crizotinib (P = .5394; HR, 1.02).
The interim survival analysis was immature with just 40% of expected deaths reported and likely confounded by the high number (87%) of chemotherapy patients who crossed over to crizotinib after progression, she noted. After adjusting for crossover, the hazard ratio suggests a survival advantage with crizotinib (HR, 0.83).
Discussant Jean-Charles Soria of Institut Gustave Roussy, Villejuif, France, agreed and said the survival times in either arm were impressive, observing that just two years ago survival in second-line ALK-positive NSCLC was just nine months.
"This is really changing the natural history of the disease," he said.
Crizotinib, an oral, first in class ALK inhibitor, was given accelerated approval in 2011 in the United States to treat advanced ALK-positive NSCLC but is not approved in Europe, where regulatory agencies have required data from the randomized trial.
"While the U.S. treats, Europe randomizes," Dr. Soria lamented to a loud round of laughter.
He observed that worldwide use of crizotinib will require that several financial and practical issues surrounding implementation of molecular testing in daily practice be addressed including the optimal technique, type of sample, and tissue availability.
Testing for epidermal growth factor receptor, another molecular alteration that directs targeted therapy in lung cancer, "should not compete with ALK," he said, adding that multiplexing test strategies "are key."
Investigators at 105 sites across 21 countries in Europe, the Americas, and Asia-Pacific, randomized 173 patients to crizotinib 250 mg twice-daily in a 21-day cycle and 174 patients to chemotherapy containing pemetrexed 500 mg/m2 or docetaxel 75 mg/m2 given intravenously on day 1 of a 21-day cycle.
Treatment duration varied significantly, with patients receiving a median of 11 cycles of crizotinib vs. 4 cycles of chemotherapy. This may have influenced the higher number of all-cause deaths among crizotinib patients (25 deaths vs. 7 deaths), said Dr. Shaw, a thoracic oncologist at Massachusetts General Hospital Cancer Center in Boston.
Crizotinib patients were more likely than were chemotherapy patients to experience the now well-known side effect of visual disturbances (any grade 60% vs. 9%), as well as diarrhea, nausea, elevated transaminases (16% grade 3/4 ), edema, upper respiratory infection, dysgeusia, and dizziness.
In contrast, fatigue, alopecia, dyspnea, and rash were more common in those receiving chemotherapy.
Despite the fact that patients on crizotinib experienced more nausea and vomiting, antiemetic use was significantly higher in the chemotherapy arm (67% vs. 20%), observed Dr. Shaw, who said the majority of adverse events were grades 1/2, generally manageable, and tolerable.
This was reflected in patient-reported lung cancer symptoms and quality of life. Based on the EORTC Quality of Life Questionnaire (QLQ C-30) and QLQ-LC 13, crizotinib patients had greater improvement from baseline in cough, dyspnea, fatigue, alopecia, insomnia, and pain as well as global quality of life (both P less than .0001).
"This is a compound with very mild toxicity," commented Dr. Soria.
He said clinicians need to be aware of crizotinib’s distinct side effect profile, including other rare events such as renal cysts, pneumonitis, asymptomatic bradycardia, and low testosterone, "although we don’t really know if it impacts sexual life."
The topic of hypogonadism was raised in a separate session on second-generation ALK inhibitors at the meeting and in a recent report of rapid-onset hypogonadism secondary to crizotinib use in 19 men with metastatic NSCLC (Cancer 2012 [doi:10.1002/cncr.27450]).
Dr. Shaw said in an interview that the study was small and "requires a lot more validation." Although testosterone levels were not checked in PROFILE 1007, it is being done for the next generation of ALK inhibitors, she added.
Dr. Soria said resistance to crizotinib will become a problem with increasing worldwide use, and that strategies to counter this may include the second-generation ALK inhibitors, increased crizotinib dosing, and crizotinib plus ablative therapy given the poor penetration of crizotinib in the brain.
Brain metastases were present in 35% of patients in both arms. Three-fourths of patients were never smokers, roughly 95% had adenocarcinoma, and their median age was about 50 years.
Dr. Shaw reported an advisory relationship with Pfizer, Ariad, Chugai, Novartis, and Daiichi-Sankyo and research funding from AstraZeneca and Novartis. Dr. Soria reported consultancy fees and steering committee activities with several firms including Pfizer, which sponsored the study.
VIENNA – Long-awaited data from the phase III PROFILE 1007 confirm that crizotinib provides superior progression-free survival and responses, compared with second-line chemotherapy in advanced anaplastic lymphoma kinase–positive non–small cell lung cancer.
Median progression-free survival more than doubled from 3.0 months with single-agent chemotherapy to 7.7 months with crizotinib, according to an independent radiologic review (P value less than .0001; hazard ratio, 0.49).
Crizotinib (Xalkori) remained superior regardless of whether chemotherapy contained docetaxel (Taxotere) (7.7 vs. 2.6 months; P less than .0001) or pemetrexed (Alimta) (7.7 vs. 4.2; P = .0004), an agent previously shown to be effective against ALK-positive NSCLC.
The overall response rate was 65.3% for crizotinib and 19.5% for chemotherapy in the intent to treat population of 347 patients (overall response rate ratio 3.4; P less than .0001).
Crizotinib was also associated with significantly greater improvement in lung cancer symptoms and quality of life, Dr. Alice Shaw reported during a presidential symposium at the joint congress of the European Cancer Organization, the European Society for Medical Oncology, and the European Society for Radiotherapy and Oncology.
"Taken together, these results establish crizotinib as the standard of care for patients with advanced, previously treated ALK-positive non–small cell lung cancer," she said.
ALK rearrangements are present in about 5% of lung cancers, typically in younger, never smokers.
Overall survival in the study was 22.8 months for chemotherapy and 20.3 months for crizotinib (P = .5394; HR, 1.02).
The interim survival analysis was immature with just 40% of expected deaths reported and likely confounded by the high number (87%) of chemotherapy patients who crossed over to crizotinib after progression, she noted. After adjusting for crossover, the hazard ratio suggests a survival advantage with crizotinib (HR, 0.83).
Discussant Jean-Charles Soria of Institut Gustave Roussy, Villejuif, France, agreed and said the survival times in either arm were impressive, observing that just two years ago survival in second-line ALK-positive NSCLC was just nine months.
"This is really changing the natural history of the disease," he said.
Crizotinib, an oral, first in class ALK inhibitor, was given accelerated approval in 2011 in the United States to treat advanced ALK-positive NSCLC but is not approved in Europe, where regulatory agencies have required data from the randomized trial.
"While the U.S. treats, Europe randomizes," Dr. Soria lamented to a loud round of laughter.
He observed that worldwide use of crizotinib will require that several financial and practical issues surrounding implementation of molecular testing in daily practice be addressed including the optimal technique, type of sample, and tissue availability.
Testing for epidermal growth factor receptor, another molecular alteration that directs targeted therapy in lung cancer, "should not compete with ALK," he said, adding that multiplexing test strategies "are key."
Investigators at 105 sites across 21 countries in Europe, the Americas, and Asia-Pacific, randomized 173 patients to crizotinib 250 mg twice-daily in a 21-day cycle and 174 patients to chemotherapy containing pemetrexed 500 mg/m2 or docetaxel 75 mg/m2 given intravenously on day 1 of a 21-day cycle.
Treatment duration varied significantly, with patients receiving a median of 11 cycles of crizotinib vs. 4 cycles of chemotherapy. This may have influenced the higher number of all-cause deaths among crizotinib patients (25 deaths vs. 7 deaths), said Dr. Shaw, a thoracic oncologist at Massachusetts General Hospital Cancer Center in Boston.
Crizotinib patients were more likely than were chemotherapy patients to experience the now well-known side effect of visual disturbances (any grade 60% vs. 9%), as well as diarrhea, nausea, elevated transaminases (16% grade 3/4 ), edema, upper respiratory infection, dysgeusia, and dizziness.
In contrast, fatigue, alopecia, dyspnea, and rash were more common in those receiving chemotherapy.
Despite the fact that patients on crizotinib experienced more nausea and vomiting, antiemetic use was significantly higher in the chemotherapy arm (67% vs. 20%), observed Dr. Shaw, who said the majority of adverse events were grades 1/2, generally manageable, and tolerable.
This was reflected in patient-reported lung cancer symptoms and quality of life. Based on the EORTC Quality of Life Questionnaire (QLQ C-30) and QLQ-LC 13, crizotinib patients had greater improvement from baseline in cough, dyspnea, fatigue, alopecia, insomnia, and pain as well as global quality of life (both P less than .0001).
"This is a compound with very mild toxicity," commented Dr. Soria.
He said clinicians need to be aware of crizotinib’s distinct side effect profile, including other rare events such as renal cysts, pneumonitis, asymptomatic bradycardia, and low testosterone, "although we don’t really know if it impacts sexual life."
The topic of hypogonadism was raised in a separate session on second-generation ALK inhibitors at the meeting and in a recent report of rapid-onset hypogonadism secondary to crizotinib use in 19 men with metastatic NSCLC (Cancer 2012 [doi:10.1002/cncr.27450]).
Dr. Shaw said in an interview that the study was small and "requires a lot more validation." Although testosterone levels were not checked in PROFILE 1007, it is being done for the next generation of ALK inhibitors, she added.
Dr. Soria said resistance to crizotinib will become a problem with increasing worldwide use, and that strategies to counter this may include the second-generation ALK inhibitors, increased crizotinib dosing, and crizotinib plus ablative therapy given the poor penetration of crizotinib in the brain.
Brain metastases were present in 35% of patients in both arms. Three-fourths of patients were never smokers, roughly 95% had adenocarcinoma, and their median age was about 50 years.
Dr. Shaw reported an advisory relationship with Pfizer, Ariad, Chugai, Novartis, and Daiichi-Sankyo and research funding from AstraZeneca and Novartis. Dr. Soria reported consultancy fees and steering committee activities with several firms including Pfizer, which sponsored the study.
VIENNA – Long-awaited data from the phase III PROFILE 1007 confirm that crizotinib provides superior progression-free survival and responses, compared with second-line chemotherapy in advanced anaplastic lymphoma kinase–positive non–small cell lung cancer.
Median progression-free survival more than doubled from 3.0 months with single-agent chemotherapy to 7.7 months with crizotinib, according to an independent radiologic review (P value less than .0001; hazard ratio, 0.49).
Crizotinib (Xalkori) remained superior regardless of whether chemotherapy contained docetaxel (Taxotere) (7.7 vs. 2.6 months; P less than .0001) or pemetrexed (Alimta) (7.7 vs. 4.2; P = .0004), an agent previously shown to be effective against ALK-positive NSCLC.
The overall response rate was 65.3% for crizotinib and 19.5% for chemotherapy in the intent to treat population of 347 patients (overall response rate ratio 3.4; P less than .0001).
Crizotinib was also associated with significantly greater improvement in lung cancer symptoms and quality of life, Dr. Alice Shaw reported during a presidential symposium at the joint congress of the European Cancer Organization, the European Society for Medical Oncology, and the European Society for Radiotherapy and Oncology.
"Taken together, these results establish crizotinib as the standard of care for patients with advanced, previously treated ALK-positive non–small cell lung cancer," she said.
ALK rearrangements are present in about 5% of lung cancers, typically in younger, never smokers.
Overall survival in the study was 22.8 months for chemotherapy and 20.3 months for crizotinib (P = .5394; HR, 1.02).
The interim survival analysis was immature with just 40% of expected deaths reported and likely confounded by the high number (87%) of chemotherapy patients who crossed over to crizotinib after progression, she noted. After adjusting for crossover, the hazard ratio suggests a survival advantage with crizotinib (HR, 0.83).
Discussant Jean-Charles Soria of Institut Gustave Roussy, Villejuif, France, agreed and said the survival times in either arm were impressive, observing that just two years ago survival in second-line ALK-positive NSCLC was just nine months.
"This is really changing the natural history of the disease," he said.
Crizotinib, an oral, first in class ALK inhibitor, was given accelerated approval in 2011 in the United States to treat advanced ALK-positive NSCLC but is not approved in Europe, where regulatory agencies have required data from the randomized trial.
"While the U.S. treats, Europe randomizes," Dr. Soria lamented to a loud round of laughter.
He observed that worldwide use of crizotinib will require that several financial and practical issues surrounding implementation of molecular testing in daily practice be addressed including the optimal technique, type of sample, and tissue availability.
Testing for epidermal growth factor receptor, another molecular alteration that directs targeted therapy in lung cancer, "should not compete with ALK," he said, adding that multiplexing test strategies "are key."
Investigators at 105 sites across 21 countries in Europe, the Americas, and Asia-Pacific, randomized 173 patients to crizotinib 250 mg twice-daily in a 21-day cycle and 174 patients to chemotherapy containing pemetrexed 500 mg/m2 or docetaxel 75 mg/m2 given intravenously on day 1 of a 21-day cycle.
Treatment duration varied significantly, with patients receiving a median of 11 cycles of crizotinib vs. 4 cycles of chemotherapy. This may have influenced the higher number of all-cause deaths among crizotinib patients (25 deaths vs. 7 deaths), said Dr. Shaw, a thoracic oncologist at Massachusetts General Hospital Cancer Center in Boston.
Crizotinib patients were more likely than were chemotherapy patients to experience the now well-known side effect of visual disturbances (any grade 60% vs. 9%), as well as diarrhea, nausea, elevated transaminases (16% grade 3/4 ), edema, upper respiratory infection, dysgeusia, and dizziness.
In contrast, fatigue, alopecia, dyspnea, and rash were more common in those receiving chemotherapy.
Despite the fact that patients on crizotinib experienced more nausea and vomiting, antiemetic use was significantly higher in the chemotherapy arm (67% vs. 20%), observed Dr. Shaw, who said the majority of adverse events were grades 1/2, generally manageable, and tolerable.
This was reflected in patient-reported lung cancer symptoms and quality of life. Based on the EORTC Quality of Life Questionnaire (QLQ C-30) and QLQ-LC 13, crizotinib patients had greater improvement from baseline in cough, dyspnea, fatigue, alopecia, insomnia, and pain as well as global quality of life (both P less than .0001).
"This is a compound with very mild toxicity," commented Dr. Soria.
He said clinicians need to be aware of crizotinib’s distinct side effect profile, including other rare events such as renal cysts, pneumonitis, asymptomatic bradycardia, and low testosterone, "although we don’t really know if it impacts sexual life."
The topic of hypogonadism was raised in a separate session on second-generation ALK inhibitors at the meeting and in a recent report of rapid-onset hypogonadism secondary to crizotinib use in 19 men with metastatic NSCLC (Cancer 2012 [doi:10.1002/cncr.27450]).
Dr. Shaw said in an interview that the study was small and "requires a lot more validation." Although testosterone levels were not checked in PROFILE 1007, it is being done for the next generation of ALK inhibitors, she added.
Dr. Soria said resistance to crizotinib will become a problem with increasing worldwide use, and that strategies to counter this may include the second-generation ALK inhibitors, increased crizotinib dosing, and crizotinib plus ablative therapy given the poor penetration of crizotinib in the brain.
Brain metastases were present in 35% of patients in both arms. Three-fourths of patients were never smokers, roughly 95% had adenocarcinoma, and their median age was about 50 years.
Dr. Shaw reported an advisory relationship with Pfizer, Ariad, Chugai, Novartis, and Daiichi-Sankyo and research funding from AstraZeneca and Novartis. Dr. Soria reported consultancy fees and steering committee activities with several firms including Pfizer, which sponsored the study.
AT THE EUROPEAN SOCIETY FOR MEDICAL ONCOLOGY CONGRESS
Major Finding: Median progression-free survival was 3.0 months with chemotherapy and 7.7 months with crizotinib (P less than .0001; hazard ratio 0.49).
Data Source: Results came from a phase III study involving 318 patients with advanced ALK-positive non–small cell lung cancer.
Disclosures: Dr. Shaw reported an advisory relationship with Pfizer, Ariad, Chugai, Novartis, and Daiichi-Sankyo and research funding from AstraZeneca and Novartis.
ACCESS-EU Registry Confirms MitraClip Benefits in HF
MUNICH – One-year results of the ACCESS-EUROPE study confirm the safety and benefits of percutaneous mitral valve repair with the MitraClip in high-risk patients with heart failure, although patient selection remains a critical issue going forward.
The severity of mitral regurgitation was improved to a meaningful extent in about 80% of patients, and was accompanied by significant improvements at 1 year in New York Heart Association (NYHA) functional class, quality of life, and 6-minute walk test distance in about 70%.
"The MitraClip therapy therefore provides a treatment option for a patient population with an important unmet clinical need," Dr. Wolfgang Schillinger said at the annual congress of the European Society of Cardiology.
The MitraClip device has been approved in Europe since 2008 and implanted in more than 6,000 patients worldwide, but is not commercially available in the United States.
Dr. Schillinger pointed out that the results provide a "picture of the real-world treatment in Europe," and are consistent with those from clinical trials, even though ACCESS-EU patients were older and sicker than those in the pivotal, randomized EVEREST II trial.
The 567 patients enrolled in the ACCESS-EU registry were described as having abundant comorbidities, including coronary artery disease in 63% and moderate to severe renal failure in 42%, and severe symptoms of end-stage heart failure, with 85% in NYHA functional class III or IV. The average logistic EuroSCORE was 23, 77% presented with functional mitral regurgitation (MR), and 98% had MR grade 3+ or higher. Their mean age was 74 years.
In contrast, the average age was 67 years in the phase II EVEREST II study, where 73% of the device patients had degenerative MR. Less than half (47%) had coronary artery disease, and only 3% had moderate/severe renal failure.
Study discussant Dr. Simon Ray, with the Manchester (U.K.) Academic Health Science Centre, said ACCESS-EU confirms data from smaller registries and that the majority of MitraClip procedures are now performed in comorbid, sick patients with functional MR, and not in the patients included in EVEREST II.
"So clinical practice has evolved beyond the envelope provided by the evidenced-based, single randomized controlled trial in this field," he said.
The 2012 European Society of Cardiology (ESC) Heart Failure Guidelines state that in patients with an indication for valve repair, but judged inoperable or at unacceptably high surgical risk, percutaneous edge-to-edge repair "may be considered" in order to improve symptoms.
The key going forward is to make sure patients undergoing this procedure genuinely have severe MR, that the assessment of operative risk reflects that of surgeons involved in the decision-making, and that the procedure is only done to improve symptoms, Dr. Ray said.
"There is no evidence that percutaneous edge-to-edge repair improves survival in this patient group," he said.
The decision to choose the less invasive catheter-based therapy over surgery was left up to the 14 ACCESS-EU registry sites.
The MitraClip device was successfully implanted in 99.6% of patients, an improvement over the 86% procedural rate during early experience with the implant in EVEREST II (N. Engl. J. Med. 2011;364:1395-406).
Mortality was low at 3.4% at 30 days, "which is a very good result in view of the comorbidities and the increased risk of the procedures," said Dr. Schillinger, with the University Medical Center Göttingen, Germany.
The most frequently reported safety events were moderate to severe renal failure in 4.8% of patients and bleeding complications in 4%, and the event rates remained low even in higher-risk patients with a EuroSCORE above 20.
At 1 year, 82% of patients were free from death, 79% had MR grade 2 or lower, and 72% were NYHA class I or II.
Significant gains were also made in quality of life scores, averaging 13.5 points from baseline on the Minnesota Living with Heart Failure Questionnaire (from 41.6 to 28.1), and averaging 59.5 m (from 275 to 334 m) in the 6-minute walk test, he said.
"What this registry does, and it is very important, is to raise perhaps more questions than it provides answers, and a number of these are around patient selection," Dr. Ray said.
What’s known from the current registry and others is that 25%-35% of patients will derive little or no symptomatic benefit from percutaneous repair. What’s not clear is whether this is due to incorrect or insufficiently sophisticated assessment of valve anatomy or overestimation of the severity of the MR because quantitative techniques have not generally been used in the registries, he said. It’s also possible that patients are being included with such severe degrees of left ventricular dysfunction that they are unlikely to benefit.
"We also need to have an eye on what constitutes success, because a technically successful procedure leading to a reduction in mitral valve regurgitation in these patients is coincidental, if they do not also have some symptomatic and functional benefit," he added.
Finally, Dr. Ray called for a pragmatic randomized trial, driven by a heart team, comparing optimized medical therapy with the addition of cardiac resynchronization therapy, where indicated, against that treatment plus the MitraClip device.
The phase III COAPT (Clinical Outcomes Assessment of the MitraClip Percutaneous Therapy for High Surgical Risk Patients) trial in moderate to severe or severe functional MR patients is not yet recruiting, but will compare the MitraClip device with patients managed nonsurgically based on standard hospital practice. REALISM (Real World Expanded Multicenter Study of the MitraClip System), the phase III follow-up to EVEREST II, continues to enroll patients in the United States and Canada, with a final completion date of December 2016.
Dr. Schillinger reported receiving consulting fees/honoraria from study sponsor Abbott Vascular, as well as Abiomed, AstraZeneca, Edwards Lifesciences, Servier, and St. Jude Medical. Dr. Ray reported no relevant conflicts of interest.
The 2012 European Society of Cardiology (ESC) Heart Failure Guidelines,
MUNICH – One-year results of the ACCESS-EUROPE study confirm the safety and benefits of percutaneous mitral valve repair with the MitraClip in high-risk patients with heart failure, although patient selection remains a critical issue going forward.
The severity of mitral regurgitation was improved to a meaningful extent in about 80% of patients, and was accompanied by significant improvements at 1 year in New York Heart Association (NYHA) functional class, quality of life, and 6-minute walk test distance in about 70%.
"The MitraClip therapy therefore provides a treatment option for a patient population with an important unmet clinical need," Dr. Wolfgang Schillinger said at the annual congress of the European Society of Cardiology.
The MitraClip device has been approved in Europe since 2008 and implanted in more than 6,000 patients worldwide, but is not commercially available in the United States.
Dr. Schillinger pointed out that the results provide a "picture of the real-world treatment in Europe," and are consistent with those from clinical trials, even though ACCESS-EU patients were older and sicker than those in the pivotal, randomized EVEREST II trial.
The 567 patients enrolled in the ACCESS-EU registry were described as having abundant comorbidities, including coronary artery disease in 63% and moderate to severe renal failure in 42%, and severe symptoms of end-stage heart failure, with 85% in NYHA functional class III or IV. The average logistic EuroSCORE was 23, 77% presented with functional mitral regurgitation (MR), and 98% had MR grade 3+ or higher. Their mean age was 74 years.
In contrast, the average age was 67 years in the phase II EVEREST II study, where 73% of the device patients had degenerative MR. Less than half (47%) had coronary artery disease, and only 3% had moderate/severe renal failure.
Study discussant Dr. Simon Ray, with the Manchester (U.K.) Academic Health Science Centre, said ACCESS-EU confirms data from smaller registries and that the majority of MitraClip procedures are now performed in comorbid, sick patients with functional MR, and not in the patients included in EVEREST II.
"So clinical practice has evolved beyond the envelope provided by the evidenced-based, single randomized controlled trial in this field," he said.
The 2012 European Society of Cardiology (ESC) Heart Failure Guidelines state that in patients with an indication for valve repair, but judged inoperable or at unacceptably high surgical risk, percutaneous edge-to-edge repair "may be considered" in order to improve symptoms.
The key going forward is to make sure patients undergoing this procedure genuinely have severe MR, that the assessment of operative risk reflects that of surgeons involved in the decision-making, and that the procedure is only done to improve symptoms, Dr. Ray said.
"There is no evidence that percutaneous edge-to-edge repair improves survival in this patient group," he said.
The decision to choose the less invasive catheter-based therapy over surgery was left up to the 14 ACCESS-EU registry sites.
The MitraClip device was successfully implanted in 99.6% of patients, an improvement over the 86% procedural rate during early experience with the implant in EVEREST II (N. Engl. J. Med. 2011;364:1395-406).
Mortality was low at 3.4% at 30 days, "which is a very good result in view of the comorbidities and the increased risk of the procedures," said Dr. Schillinger, with the University Medical Center Göttingen, Germany.
The most frequently reported safety events were moderate to severe renal failure in 4.8% of patients and bleeding complications in 4%, and the event rates remained low even in higher-risk patients with a EuroSCORE above 20.
At 1 year, 82% of patients were free from death, 79% had MR grade 2 or lower, and 72% were NYHA class I or II.
Significant gains were also made in quality of life scores, averaging 13.5 points from baseline on the Minnesota Living with Heart Failure Questionnaire (from 41.6 to 28.1), and averaging 59.5 m (from 275 to 334 m) in the 6-minute walk test, he said.
"What this registry does, and it is very important, is to raise perhaps more questions than it provides answers, and a number of these are around patient selection," Dr. Ray said.
What’s known from the current registry and others is that 25%-35% of patients will derive little or no symptomatic benefit from percutaneous repair. What’s not clear is whether this is due to incorrect or insufficiently sophisticated assessment of valve anatomy or overestimation of the severity of the MR because quantitative techniques have not generally been used in the registries, he said. It’s also possible that patients are being included with such severe degrees of left ventricular dysfunction that they are unlikely to benefit.
"We also need to have an eye on what constitutes success, because a technically successful procedure leading to a reduction in mitral valve regurgitation in these patients is coincidental, if they do not also have some symptomatic and functional benefit," he added.
Finally, Dr. Ray called for a pragmatic randomized trial, driven by a heart team, comparing optimized medical therapy with the addition of cardiac resynchronization therapy, where indicated, against that treatment plus the MitraClip device.
The phase III COAPT (Clinical Outcomes Assessment of the MitraClip Percutaneous Therapy for High Surgical Risk Patients) trial in moderate to severe or severe functional MR patients is not yet recruiting, but will compare the MitraClip device with patients managed nonsurgically based on standard hospital practice. REALISM (Real World Expanded Multicenter Study of the MitraClip System), the phase III follow-up to EVEREST II, continues to enroll patients in the United States and Canada, with a final completion date of December 2016.
Dr. Schillinger reported receiving consulting fees/honoraria from study sponsor Abbott Vascular, as well as Abiomed, AstraZeneca, Edwards Lifesciences, Servier, and St. Jude Medical. Dr. Ray reported no relevant conflicts of interest.
MUNICH – One-year results of the ACCESS-EUROPE study confirm the safety and benefits of percutaneous mitral valve repair with the MitraClip in high-risk patients with heart failure, although patient selection remains a critical issue going forward.
The severity of mitral regurgitation was improved to a meaningful extent in about 80% of patients, and was accompanied by significant improvements at 1 year in New York Heart Association (NYHA) functional class, quality of life, and 6-minute walk test distance in about 70%.
"The MitraClip therapy therefore provides a treatment option for a patient population with an important unmet clinical need," Dr. Wolfgang Schillinger said at the annual congress of the European Society of Cardiology.
The MitraClip device has been approved in Europe since 2008 and implanted in more than 6,000 patients worldwide, but is not commercially available in the United States.
Dr. Schillinger pointed out that the results provide a "picture of the real-world treatment in Europe," and are consistent with those from clinical trials, even though ACCESS-EU patients were older and sicker than those in the pivotal, randomized EVEREST II trial.
The 567 patients enrolled in the ACCESS-EU registry were described as having abundant comorbidities, including coronary artery disease in 63% and moderate to severe renal failure in 42%, and severe symptoms of end-stage heart failure, with 85% in NYHA functional class III or IV. The average logistic EuroSCORE was 23, 77% presented with functional mitral regurgitation (MR), and 98% had MR grade 3+ or higher. Their mean age was 74 years.
In contrast, the average age was 67 years in the phase II EVEREST II study, where 73% of the device patients had degenerative MR. Less than half (47%) had coronary artery disease, and only 3% had moderate/severe renal failure.
Study discussant Dr. Simon Ray, with the Manchester (U.K.) Academic Health Science Centre, said ACCESS-EU confirms data from smaller registries and that the majority of MitraClip procedures are now performed in comorbid, sick patients with functional MR, and not in the patients included in EVEREST II.
"So clinical practice has evolved beyond the envelope provided by the evidenced-based, single randomized controlled trial in this field," he said.
The 2012 European Society of Cardiology (ESC) Heart Failure Guidelines state that in patients with an indication for valve repair, but judged inoperable or at unacceptably high surgical risk, percutaneous edge-to-edge repair "may be considered" in order to improve symptoms.
The key going forward is to make sure patients undergoing this procedure genuinely have severe MR, that the assessment of operative risk reflects that of surgeons involved in the decision-making, and that the procedure is only done to improve symptoms, Dr. Ray said.
"There is no evidence that percutaneous edge-to-edge repair improves survival in this patient group," he said.
The decision to choose the less invasive catheter-based therapy over surgery was left up to the 14 ACCESS-EU registry sites.
The MitraClip device was successfully implanted in 99.6% of patients, an improvement over the 86% procedural rate during early experience with the implant in EVEREST II (N. Engl. J. Med. 2011;364:1395-406).
Mortality was low at 3.4% at 30 days, "which is a very good result in view of the comorbidities and the increased risk of the procedures," said Dr. Schillinger, with the University Medical Center Göttingen, Germany.
The most frequently reported safety events were moderate to severe renal failure in 4.8% of patients and bleeding complications in 4%, and the event rates remained low even in higher-risk patients with a EuroSCORE above 20.
At 1 year, 82% of patients were free from death, 79% had MR grade 2 or lower, and 72% were NYHA class I or II.
Significant gains were also made in quality of life scores, averaging 13.5 points from baseline on the Minnesota Living with Heart Failure Questionnaire (from 41.6 to 28.1), and averaging 59.5 m (from 275 to 334 m) in the 6-minute walk test, he said.
"What this registry does, and it is very important, is to raise perhaps more questions than it provides answers, and a number of these are around patient selection," Dr. Ray said.
What’s known from the current registry and others is that 25%-35% of patients will derive little or no symptomatic benefit from percutaneous repair. What’s not clear is whether this is due to incorrect or insufficiently sophisticated assessment of valve anatomy or overestimation of the severity of the MR because quantitative techniques have not generally been used in the registries, he said. It’s also possible that patients are being included with such severe degrees of left ventricular dysfunction that they are unlikely to benefit.
"We also need to have an eye on what constitutes success, because a technically successful procedure leading to a reduction in mitral valve regurgitation in these patients is coincidental, if they do not also have some symptomatic and functional benefit," he added.
Finally, Dr. Ray called for a pragmatic randomized trial, driven by a heart team, comparing optimized medical therapy with the addition of cardiac resynchronization therapy, where indicated, against that treatment plus the MitraClip device.
The phase III COAPT (Clinical Outcomes Assessment of the MitraClip Percutaneous Therapy for High Surgical Risk Patients) trial in moderate to severe or severe functional MR patients is not yet recruiting, but will compare the MitraClip device with patients managed nonsurgically based on standard hospital practice. REALISM (Real World Expanded Multicenter Study of the MitraClip System), the phase III follow-up to EVEREST II, continues to enroll patients in the United States and Canada, with a final completion date of December 2016.
Dr. Schillinger reported receiving consulting fees/honoraria from study sponsor Abbott Vascular, as well as Abiomed, AstraZeneca, Edwards Lifesciences, Servier, and St. Jude Medical. Dr. Ray reported no relevant conflicts of interest.
The 2012 European Society of Cardiology (ESC) Heart Failure Guidelines,
The 2012 European Society of Cardiology (ESC) Heart Failure Guidelines,
AT THE ANNUAL CONGRESS OF THE EUROPEAN SOCIETY OF CARDIOLOGY
Major Finding: At 1 year, 82% of patients were alive, 79% had mitral regurgitation grade 2 or lower, and 72% were NYHA class I or II.
Data Source: This was a multicenter, prospective, observational study of 567 heart failure patients with severe mitral valve regurgitation.
Disclosures: Dr. Schillinger reported receiving consulting fees/honoraria from study sponsor Abbott Vascular, as well as Abiomed, AstraZeneca, Edwards Lifesciences, Servier, and St. Jude Medical. Dr. Ray reported no relevant conflicts of interest.
Smoking Relapse Deadly for Stroke Survivors
MUNICH – Patients who resume smoking after an ischemic stroke raise their risk of dying by roughly threefold within 1 year, a prospective, observational study has shown.
Moreover, the risk of dying increases the sooner the relapse occurs. Patients who resume smoking within 10 days of leaving the hospital are five times more likely to die within a year than are those who remain smoke free.
"Smoking relapse is extremely dangerous after an acute ischemic stroke," said Dr. Furio Colivicchi of the cardiovascular department at San Filippo Neri Hospital, Rome.
Cardiologists at San Filippo, in collaboration with neurologists from the Santa Lucia Foundation of Rome, enrolled 921 consecutive active smokers who ceased smoking after admission to the hospital for acute ischemic stroke and reported being motivated to continue abstaining once discharged.
All patients received a brief in-hospital smoking cessation counseling session lasting 5-20 minutes and delivered by trained nurses (73%) or physicians (27%).
Patients did not receive any specific postdischarge support or pharmacotherapy for smoking cessation. One-third of patients (34%), however, were referred to a hospital-based rehabilitation program after their stroke.
The cohort of 584 men and 337 women had an average National Institutes of Health Stroke Scale score of 9.1, 11% had had a previous stroke, 18% had a previous myocardial infarction, 69% had hypertension, and 20% were obese. Their average age was 67 years.
During the 12-month follow-up, 54% of all patients resumed regular cigarette smoking, with 50% relapsing within 3 weeks of discharge, Dr. Colivicchi reported at the annual congress of the European Society of Cardiology.
Patients who relapsed were significantly more likely to be older (69 years vs. 65 years) and female (44% vs. 28%), and were less likely to do so if referred to a hospital-based stroke rehabilitation program (25% vs. 44%), all highly significant differences.
During the 12-month follow-up, 89 patients (9.7%) died. Most of the deaths were due to ischemic events, both coronary and stroke recurrences, Dr. Colivicchi told the media at the meeting.
"The causal link between smoke and further ischemic events is complex," he said. "But we do know that smoking has a negative impact on the cardiovascular system, and it increases the ability of the platelets to aggregate, for instance, which is a crucial point in these ischemic syndromes."
After adjustment for confounding interactions including clinical variables and variables related to the acute event, a strong relationship was found between smoking relapse and all-cause mortality, Dr. Colivicchi said. The risk of death was 5.1-fold higher at 10 days, 3.8-fold higher at 120 days, and 2.6-fold higher at roughly 1 year.
A linear correlation exists between the number of cigarettes and the probability of suffering an acute cardiovascular event, but even small amounts, such as fewer than five cigarettes per day, have been linked to increased cardiovascular events, he noted. Most of the patients in the study were heavy smokers, smoking more than 10 cigarettes per day prior to the index event and typically relapsing to their original amount.
"We must be very careful and provide a more comprehensive approach because individual counseling is not fully effective if it is not followed by postdischarge support for this specific problem and possibly, in selected cases, by pharmacological treatment aimed at reducing the risk of relapse," he said.
A recent study in 4,834 patients with acute coronary syndrome (ACS) reported that while 20% were smokers at the time of their ACS, only 24% received any smoking intervention from their general practitioner within 3 months of the event. Of these, 9% received advice only and 15% received pharmacological intervention (Eur. J. Prev. Cardiol. 2012 Sept. 5 [epub ahead of print]).
Dr. Colivicchi reported no relevant financial conflicts.
Cardiologists, neurologists, in-hospital smoking cessation counseling session, National Institutes of Health Stroke Scale, annual congress of the European Society of Cardiology, hospital-based stroke rehabilitation program,
MUNICH – Patients who resume smoking after an ischemic stroke raise their risk of dying by roughly threefold within 1 year, a prospective, observational study has shown.
Moreover, the risk of dying increases the sooner the relapse occurs. Patients who resume smoking within 10 days of leaving the hospital are five times more likely to die within a year than are those who remain smoke free.
"Smoking relapse is extremely dangerous after an acute ischemic stroke," said Dr. Furio Colivicchi of the cardiovascular department at San Filippo Neri Hospital, Rome.
Cardiologists at San Filippo, in collaboration with neurologists from the Santa Lucia Foundation of Rome, enrolled 921 consecutive active smokers who ceased smoking after admission to the hospital for acute ischemic stroke and reported being motivated to continue abstaining once discharged.
All patients received a brief in-hospital smoking cessation counseling session lasting 5-20 minutes and delivered by trained nurses (73%) or physicians (27%).
Patients did not receive any specific postdischarge support or pharmacotherapy for smoking cessation. One-third of patients (34%), however, were referred to a hospital-based rehabilitation program after their stroke.
The cohort of 584 men and 337 women had an average National Institutes of Health Stroke Scale score of 9.1, 11% had had a previous stroke, 18% had a previous myocardial infarction, 69% had hypertension, and 20% were obese. Their average age was 67 years.
During the 12-month follow-up, 54% of all patients resumed regular cigarette smoking, with 50% relapsing within 3 weeks of discharge, Dr. Colivicchi reported at the annual congress of the European Society of Cardiology.
Patients who relapsed were significantly more likely to be older (69 years vs. 65 years) and female (44% vs. 28%), and were less likely to do so if referred to a hospital-based stroke rehabilitation program (25% vs. 44%), all highly significant differences.
During the 12-month follow-up, 89 patients (9.7%) died. Most of the deaths were due to ischemic events, both coronary and stroke recurrences, Dr. Colivicchi told the media at the meeting.
"The causal link between smoke and further ischemic events is complex," he said. "But we do know that smoking has a negative impact on the cardiovascular system, and it increases the ability of the platelets to aggregate, for instance, which is a crucial point in these ischemic syndromes."
After adjustment for confounding interactions including clinical variables and variables related to the acute event, a strong relationship was found between smoking relapse and all-cause mortality, Dr. Colivicchi said. The risk of death was 5.1-fold higher at 10 days, 3.8-fold higher at 120 days, and 2.6-fold higher at roughly 1 year.
A linear correlation exists between the number of cigarettes and the probability of suffering an acute cardiovascular event, but even small amounts, such as fewer than five cigarettes per day, have been linked to increased cardiovascular events, he noted. Most of the patients in the study were heavy smokers, smoking more than 10 cigarettes per day prior to the index event and typically relapsing to their original amount.
"We must be very careful and provide a more comprehensive approach because individual counseling is not fully effective if it is not followed by postdischarge support for this specific problem and possibly, in selected cases, by pharmacological treatment aimed at reducing the risk of relapse," he said.
A recent study in 4,834 patients with acute coronary syndrome (ACS) reported that while 20% were smokers at the time of their ACS, only 24% received any smoking intervention from their general practitioner within 3 months of the event. Of these, 9% received advice only and 15% received pharmacological intervention (Eur. J. Prev. Cardiol. 2012 Sept. 5 [epub ahead of print]).
Dr. Colivicchi reported no relevant financial conflicts.
MUNICH – Patients who resume smoking after an ischemic stroke raise their risk of dying by roughly threefold within 1 year, a prospective, observational study has shown.
Moreover, the risk of dying increases the sooner the relapse occurs. Patients who resume smoking within 10 days of leaving the hospital are five times more likely to die within a year than are those who remain smoke free.
"Smoking relapse is extremely dangerous after an acute ischemic stroke," said Dr. Furio Colivicchi of the cardiovascular department at San Filippo Neri Hospital, Rome.
Cardiologists at San Filippo, in collaboration with neurologists from the Santa Lucia Foundation of Rome, enrolled 921 consecutive active smokers who ceased smoking after admission to the hospital for acute ischemic stroke and reported being motivated to continue abstaining once discharged.
All patients received a brief in-hospital smoking cessation counseling session lasting 5-20 minutes and delivered by trained nurses (73%) or physicians (27%).
Patients did not receive any specific postdischarge support or pharmacotherapy for smoking cessation. One-third of patients (34%), however, were referred to a hospital-based rehabilitation program after their stroke.
The cohort of 584 men and 337 women had an average National Institutes of Health Stroke Scale score of 9.1, 11% had had a previous stroke, 18% had a previous myocardial infarction, 69% had hypertension, and 20% were obese. Their average age was 67 years.
During the 12-month follow-up, 54% of all patients resumed regular cigarette smoking, with 50% relapsing within 3 weeks of discharge, Dr. Colivicchi reported at the annual congress of the European Society of Cardiology.
Patients who relapsed were significantly more likely to be older (69 years vs. 65 years) and female (44% vs. 28%), and were less likely to do so if referred to a hospital-based stroke rehabilitation program (25% vs. 44%), all highly significant differences.
During the 12-month follow-up, 89 patients (9.7%) died. Most of the deaths were due to ischemic events, both coronary and stroke recurrences, Dr. Colivicchi told the media at the meeting.
"The causal link between smoke and further ischemic events is complex," he said. "But we do know that smoking has a negative impact on the cardiovascular system, and it increases the ability of the platelets to aggregate, for instance, which is a crucial point in these ischemic syndromes."
After adjustment for confounding interactions including clinical variables and variables related to the acute event, a strong relationship was found between smoking relapse and all-cause mortality, Dr. Colivicchi said. The risk of death was 5.1-fold higher at 10 days, 3.8-fold higher at 120 days, and 2.6-fold higher at roughly 1 year.
A linear correlation exists between the number of cigarettes and the probability of suffering an acute cardiovascular event, but even small amounts, such as fewer than five cigarettes per day, have been linked to increased cardiovascular events, he noted. Most of the patients in the study were heavy smokers, smoking more than 10 cigarettes per day prior to the index event and typically relapsing to their original amount.
"We must be very careful and provide a more comprehensive approach because individual counseling is not fully effective if it is not followed by postdischarge support for this specific problem and possibly, in selected cases, by pharmacological treatment aimed at reducing the risk of relapse," he said.
A recent study in 4,834 patients with acute coronary syndrome (ACS) reported that while 20% were smokers at the time of their ACS, only 24% received any smoking intervention from their general practitioner within 3 months of the event. Of these, 9% received advice only and 15% received pharmacological intervention (Eur. J. Prev. Cardiol. 2012 Sept. 5 [epub ahead of print]).
Dr. Colivicchi reported no relevant financial conflicts.
Cardiologists, neurologists, in-hospital smoking cessation counseling session, National Institutes of Health Stroke Scale, annual congress of the European Society of Cardiology, hospital-based stroke rehabilitation program,
Cardiologists, neurologists, in-hospital smoking cessation counseling session, National Institutes of Health Stroke Scale, annual congress of the European Society of Cardiology, hospital-based stroke rehabilitation program,
AT THE ANNUAL CONGRESS OF THE EUROPEAN SOCIETY OF CARDIOLOGY
Major Finding: Stroke survivors who resume smoking have a threefold higher risk of dying within 1 year.
Data Source: Data are from a prospective, observational study of 921 consecutive stroke survivors who smoke.
Disclosures: Dr. Colivicchi reported no relevant financial conflicts.
Real-World TAVI Outcomes Spot On With Clinical Trial Results
MUNICH – In-hospital mortality and complications following transcatheter aortic valve implantation in the real-world setting are comparable with those achieved in randomized controlled studies, according to data from the first large-scale national registry capturing surgical and catheter-based procedures.
"In high-risk patients, the in-hospital mortality with TAVI is at least as good, if not better, as with the surgical approach," said Dr. Christian Hamm, who presented data from 13,860 patients in the German Aortic Valve Registry (GARY during a hotline session at the annual congress of the European Society of Cardiology.
In-hospital mortality was 2.2% for conventional aortic valve replacement surgery alone, 4.6% for conventional surgery with coronary artery bypass grafting (CABG), 5.5% for TAVI using a transvascular approach, and 7.8% for TAVI with a transapical approach.
After adjusting for the expected higher risk profile of TAVI patients, the risk of in-hospital death was not increased with transvascular TAVI, compared with surgery alone, although there was a trend toward increased risk with transapical TAVI in both younger patients and those aged 75 years and older, said Dr. Hamm, medical director of the Kerckhoff Heart and Thorax Centre, Bad Nauheim, Germany.
When asked by the media whether the higher mortality may be diminishing use of the transapical approach, GARY coauthor Dr. Friedrich-Wilhelm Mohr said that similar rates have been seen in the source registry and that these patients tend to have slightly more comorbidities and vascular disease.
"The current data in 2012 do not show a pull back," said Dr. Mohr, medical director of the Leipzig (Germany) Heart Center. "It’s almost the same situation as here: two-thirds transfemoral and one-third transapical."
Consistent with earlier observations, the rate of cerebrovascular events was lowest in patients undergoing surgery without CABG at 2.2% and was "in the range of 3.5%" for all other groups, Dr. Hamm reported.
Discussant Dr. Olaf Wendler said it’s convincing that cerebrovascular complications are lower than in the landmark PARTNER (Placement of Aortic Transcatheter Valves) trial, which reported a 5% major stroke rate among TAVI patients at 30 days.
"This may be less of a problem than we thought about transcatheter-valve treatment in the past," he said. "However, again we don’t have all the details, definitions of the adverse events, and we don’t have a clear idea of how adverse events were adjudicated in this registry."
Rates of vascular complications and new onset atrioventricular (AV) blockage were highest after transvascular TAVI, while renal failure was most common after the transapical approach, said Dr. Wendler, professor at King’s College Hospital in London.
Specifically, vascular complications were reported in 12% of transvascular patients, compared with 2.5% for the transapical approach, 2% for surgery plus CABG, and 1% for surgery alone.
Residual postimplant aortic regurgitation, which has been linked to long-term TAVI outcome, "seemed to be excellent because more than 90% of patients had no or grade I regurgitation," Dr. Hamm said. Only 7% of transvascular and 3% of transapical patients had grade II regurgitation, and only 1% of transapical and no transvascular patients had grade III or IV regurgitation.
Although between-valve comparisons were limited since the CoreValve was not implanted transapically, grade I or II aortic regurgitation was more common with the CoreValve (70%) than with the Edwards prosthesis (45.7%).
Despite the increasing shift of TAVI in lower-risk patients, data from GARY show that TAVI is being performed predominantly in high-risk patients, as recommended in various guidelines, Dr. Hamm said.
Participation in GARY is voluntary, with 92 of 99 German centers currently taking part. As of July 2012, more than 26,000 patients were included, of whom 23% were TAVI patients.
The current analysis included 13,860 patients from 53 cardiac surgery units and 69 cardiology units. Of these patients, 6,523 underwent surgery alone, 3,462 surgery plus CABG, 2,694 transvascular TAVI, and 1,181 transapical TAVI.
At baseline, TAVI patients were significantly older than surgical patients (average of 81 years transvascular and 80.3 years transapical vs. 68 years surgical); had significantly more comorbidities including atrial fibrillation, hypertension, and diabetes; and were significantly more likely to have a left ventricular ejection fraction below 30%.
Roughly half of elderly patients more than 75 years of age now receive TAVI in Germany, which is quite impressive and by far a higher number than any other country worldwide, said Dr. Wendler.
German investigators also have developed a novel risk scoring system called the AKL score, which, unlike the logistic EuroSCORE or Society of Thoracic Surgeons (STS) risk score, is based only on patients with aortic valve disease.
"The EuroSCORE, as many of us know, is not very suitable in this scenario," Dr. Hamm said.
When the GARY authors compared observed vs. expected in-hospital mortality based on patients’ EuroSCORE, the observed risk for mortality was much lower than predicted by the EuroSCORE.
When the same analysis was performed using the AKL score, however, the observed and expected mortality outcomes were very similar, suggesting the "AKL score much better reflects the real outcome of the patients," he said.
Dr. Wendler remarked that in low-risk patients, however, the observed in-hospital mortality was higher than what was predicted, "questioning if this is the right treatment for this group of patients."
GARY is supported by the German Heart Foundation and unrestricted grants from heart valve manufacturers. Dr. Hamm disclosed honoraria from Medtronic and Edwards Lifesciences and participation in clinical trials with Medtronic, Edwards, Symetis, and JenaValve. Dr. Mohr reported no conflicts of interest. Dr. Wendler reported research ties with Edwards and consulting for Edwards and St. Jude Medical.
MUNICH – In-hospital mortality and complications following transcatheter aortic valve implantation in the real-world setting are comparable with those achieved in randomized controlled studies, according to data from the first large-scale national registry capturing surgical and catheter-based procedures.
"In high-risk patients, the in-hospital mortality with TAVI is at least as good, if not better, as with the surgical approach," said Dr. Christian Hamm, who presented data from 13,860 patients in the German Aortic Valve Registry (GARY during a hotline session at the annual congress of the European Society of Cardiology.
In-hospital mortality was 2.2% for conventional aortic valve replacement surgery alone, 4.6% for conventional surgery with coronary artery bypass grafting (CABG), 5.5% for TAVI using a transvascular approach, and 7.8% for TAVI with a transapical approach.
After adjusting for the expected higher risk profile of TAVI patients, the risk of in-hospital death was not increased with transvascular TAVI, compared with surgery alone, although there was a trend toward increased risk with transapical TAVI in both younger patients and those aged 75 years and older, said Dr. Hamm, medical director of the Kerckhoff Heart and Thorax Centre, Bad Nauheim, Germany.
When asked by the media whether the higher mortality may be diminishing use of the transapical approach, GARY coauthor Dr. Friedrich-Wilhelm Mohr said that similar rates have been seen in the source registry and that these patients tend to have slightly more comorbidities and vascular disease.
"The current data in 2012 do not show a pull back," said Dr. Mohr, medical director of the Leipzig (Germany) Heart Center. "It’s almost the same situation as here: two-thirds transfemoral and one-third transapical."
Consistent with earlier observations, the rate of cerebrovascular events was lowest in patients undergoing surgery without CABG at 2.2% and was "in the range of 3.5%" for all other groups, Dr. Hamm reported.
Discussant Dr. Olaf Wendler said it’s convincing that cerebrovascular complications are lower than in the landmark PARTNER (Placement of Aortic Transcatheter Valves) trial, which reported a 5% major stroke rate among TAVI patients at 30 days.
"This may be less of a problem than we thought about transcatheter-valve treatment in the past," he said. "However, again we don’t have all the details, definitions of the adverse events, and we don’t have a clear idea of how adverse events were adjudicated in this registry."
Rates of vascular complications and new onset atrioventricular (AV) blockage were highest after transvascular TAVI, while renal failure was most common after the transapical approach, said Dr. Wendler, professor at King’s College Hospital in London.
Specifically, vascular complications were reported in 12% of transvascular patients, compared with 2.5% for the transapical approach, 2% for surgery plus CABG, and 1% for surgery alone.
Residual postimplant aortic regurgitation, which has been linked to long-term TAVI outcome, "seemed to be excellent because more than 90% of patients had no or grade I regurgitation," Dr. Hamm said. Only 7% of transvascular and 3% of transapical patients had grade II regurgitation, and only 1% of transapical and no transvascular patients had grade III or IV regurgitation.
Although between-valve comparisons were limited since the CoreValve was not implanted transapically, grade I or II aortic regurgitation was more common with the CoreValve (70%) than with the Edwards prosthesis (45.7%).
Despite the increasing shift of TAVI in lower-risk patients, data from GARY show that TAVI is being performed predominantly in high-risk patients, as recommended in various guidelines, Dr. Hamm said.
Participation in GARY is voluntary, with 92 of 99 German centers currently taking part. As of July 2012, more than 26,000 patients were included, of whom 23% were TAVI patients.
The current analysis included 13,860 patients from 53 cardiac surgery units and 69 cardiology units. Of these patients, 6,523 underwent surgery alone, 3,462 surgery plus CABG, 2,694 transvascular TAVI, and 1,181 transapical TAVI.
At baseline, TAVI patients were significantly older than surgical patients (average of 81 years transvascular and 80.3 years transapical vs. 68 years surgical); had significantly more comorbidities including atrial fibrillation, hypertension, and diabetes; and were significantly more likely to have a left ventricular ejection fraction below 30%.
Roughly half of elderly patients more than 75 years of age now receive TAVI in Germany, which is quite impressive and by far a higher number than any other country worldwide, said Dr. Wendler.
German investigators also have developed a novel risk scoring system called the AKL score, which, unlike the logistic EuroSCORE or Society of Thoracic Surgeons (STS) risk score, is based only on patients with aortic valve disease.
"The EuroSCORE, as many of us know, is not very suitable in this scenario," Dr. Hamm said.
When the GARY authors compared observed vs. expected in-hospital mortality based on patients’ EuroSCORE, the observed risk for mortality was much lower than predicted by the EuroSCORE.
When the same analysis was performed using the AKL score, however, the observed and expected mortality outcomes were very similar, suggesting the "AKL score much better reflects the real outcome of the patients," he said.
Dr. Wendler remarked that in low-risk patients, however, the observed in-hospital mortality was higher than what was predicted, "questioning if this is the right treatment for this group of patients."
GARY is supported by the German Heart Foundation and unrestricted grants from heart valve manufacturers. Dr. Hamm disclosed honoraria from Medtronic and Edwards Lifesciences and participation in clinical trials with Medtronic, Edwards, Symetis, and JenaValve. Dr. Mohr reported no conflicts of interest. Dr. Wendler reported research ties with Edwards and consulting for Edwards and St. Jude Medical.
MUNICH – In-hospital mortality and complications following transcatheter aortic valve implantation in the real-world setting are comparable with those achieved in randomized controlled studies, according to data from the first large-scale national registry capturing surgical and catheter-based procedures.
"In high-risk patients, the in-hospital mortality with TAVI is at least as good, if not better, as with the surgical approach," said Dr. Christian Hamm, who presented data from 13,860 patients in the German Aortic Valve Registry (GARY during a hotline session at the annual congress of the European Society of Cardiology.
In-hospital mortality was 2.2% for conventional aortic valve replacement surgery alone, 4.6% for conventional surgery with coronary artery bypass grafting (CABG), 5.5% for TAVI using a transvascular approach, and 7.8% for TAVI with a transapical approach.
After adjusting for the expected higher risk profile of TAVI patients, the risk of in-hospital death was not increased with transvascular TAVI, compared with surgery alone, although there was a trend toward increased risk with transapical TAVI in both younger patients and those aged 75 years and older, said Dr. Hamm, medical director of the Kerckhoff Heart and Thorax Centre, Bad Nauheim, Germany.
When asked by the media whether the higher mortality may be diminishing use of the transapical approach, GARY coauthor Dr. Friedrich-Wilhelm Mohr said that similar rates have been seen in the source registry and that these patients tend to have slightly more comorbidities and vascular disease.
"The current data in 2012 do not show a pull back," said Dr. Mohr, medical director of the Leipzig (Germany) Heart Center. "It’s almost the same situation as here: two-thirds transfemoral and one-third transapical."
Consistent with earlier observations, the rate of cerebrovascular events was lowest in patients undergoing surgery without CABG at 2.2% and was "in the range of 3.5%" for all other groups, Dr. Hamm reported.
Discussant Dr. Olaf Wendler said it’s convincing that cerebrovascular complications are lower than in the landmark PARTNER (Placement of Aortic Transcatheter Valves) trial, which reported a 5% major stroke rate among TAVI patients at 30 days.
"This may be less of a problem than we thought about transcatheter-valve treatment in the past," he said. "However, again we don’t have all the details, definitions of the adverse events, and we don’t have a clear idea of how adverse events were adjudicated in this registry."
Rates of vascular complications and new onset atrioventricular (AV) blockage were highest after transvascular TAVI, while renal failure was most common after the transapical approach, said Dr. Wendler, professor at King’s College Hospital in London.
Specifically, vascular complications were reported in 12% of transvascular patients, compared with 2.5% for the transapical approach, 2% for surgery plus CABG, and 1% for surgery alone.
Residual postimplant aortic regurgitation, which has been linked to long-term TAVI outcome, "seemed to be excellent because more than 90% of patients had no or grade I regurgitation," Dr. Hamm said. Only 7% of transvascular and 3% of transapical patients had grade II regurgitation, and only 1% of transapical and no transvascular patients had grade III or IV regurgitation.
Although between-valve comparisons were limited since the CoreValve was not implanted transapically, grade I or II aortic regurgitation was more common with the CoreValve (70%) than with the Edwards prosthesis (45.7%).
Despite the increasing shift of TAVI in lower-risk patients, data from GARY show that TAVI is being performed predominantly in high-risk patients, as recommended in various guidelines, Dr. Hamm said.
Participation in GARY is voluntary, with 92 of 99 German centers currently taking part. As of July 2012, more than 26,000 patients were included, of whom 23% were TAVI patients.
The current analysis included 13,860 patients from 53 cardiac surgery units and 69 cardiology units. Of these patients, 6,523 underwent surgery alone, 3,462 surgery plus CABG, 2,694 transvascular TAVI, and 1,181 transapical TAVI.
At baseline, TAVI patients were significantly older than surgical patients (average of 81 years transvascular and 80.3 years transapical vs. 68 years surgical); had significantly more comorbidities including atrial fibrillation, hypertension, and diabetes; and were significantly more likely to have a left ventricular ejection fraction below 30%.
Roughly half of elderly patients more than 75 years of age now receive TAVI in Germany, which is quite impressive and by far a higher number than any other country worldwide, said Dr. Wendler.
German investigators also have developed a novel risk scoring system called the AKL score, which, unlike the logistic EuroSCORE or Society of Thoracic Surgeons (STS) risk score, is based only on patients with aortic valve disease.
"The EuroSCORE, as many of us know, is not very suitable in this scenario," Dr. Hamm said.
When the GARY authors compared observed vs. expected in-hospital mortality based on patients’ EuroSCORE, the observed risk for mortality was much lower than predicted by the EuroSCORE.
When the same analysis was performed using the AKL score, however, the observed and expected mortality outcomes were very similar, suggesting the "AKL score much better reflects the real outcome of the patients," he said.
Dr. Wendler remarked that in low-risk patients, however, the observed in-hospital mortality was higher than what was predicted, "questioning if this is the right treatment for this group of patients."
GARY is supported by the German Heart Foundation and unrestricted grants from heart valve manufacturers. Dr. Hamm disclosed honoraria from Medtronic and Edwards Lifesciences and participation in clinical trials with Medtronic, Edwards, Symetis, and JenaValve. Dr. Mohr reported no conflicts of interest. Dr. Wendler reported research ties with Edwards and consulting for Edwards and St. Jude Medical.
AT THE ANNUAL CONGRESS OF THE EUROPEAN SOCIETY OF CARDIOLOGY
Major Finding: In-hospital mortality was 2.2% for conventional aortic valve replacement surgery, 4.6% for conventional surgery with coronary artery bypass grafting, 5.5% for transvascular TAVI, and 7.8% for transapical TAVI.
Data Source: Data are from 13,860 patients treated with TAVI in 2011 in the German Aortic Valve Registry.
Disclosures: GARY is supported by the German Heart Foundation and unrestricted grants from heart valve manufacturers. Dr. Hamm disclosed honoraria from Medtronic and Edwards Lifesciences and participation in clinical trials with Medtronic, Edwards, Symetis, and JenaValve. Dr. Mohr reported no conflicts of interest. Dr. Wendler reported research ties with Edwards and consulting for Edwards and St. Jude Medical.
Readmissions Similar for Endovascular, Open Lower-Limb Interventions
MILWAUKEE – Less invasive lower-extremity endovascular interventions do not reduce hospital readmissions among patients with peripheral artery disease, according to an analysis of the Cerner Health Facts database.
The 30-day readmission rate was 13.9% for patients who underwent open surgery and 15.3% for those who had an endovascular procedure.
Lead author Dr. Todd Vogel expressed surprise that the two approaches were relatively equal, adding that, "I thought with endo, we’re doing less, they’d come back more."
The common practice of staging lower-limb endovascular interventions is creating concerns that use of hospital readmissions as a quality outcome measure for reimbursement may not accurately identify planned readmissions or quality of care.
Session moderator Dr. Patrick Geraghty said in an interview that lower-extremity intervention outcomes "are probably the most complex and difficult to define outcomes issue for all of vascular surgery," as compared with carotid and aortic aneurysms, and that this is already reflected in efforts proposed by the National Surgical Quality Improvement Program (NSQIP) and the Centers for Medicare and Medicaid Services (CMS).
"Lower-extremity readmission is going to be a real hot-button discussion because we already know it’s substantial," he said. "If I do a stent graft for someone with leg ischemia and the flow improves and they go home on post-op day 1, and I bring them back 10 days later for a planned debridement of a toe ulcer that we’d been looking at, was that bad? Was that poor care, something I should be penalized for?
"Or was it just good care, but it didn’t fit into CMS’s box of everything should be done within one admission and that any readmission is therefore bad?"
The current analysis is unique in that utilizes electronic medical record (EMR) data to provide real-world outcomes for lower-limb interventions, said Dr. Geraghty, a vascular surgeon with Barnes-Jewish Hospital in St. Louis.
"I think we’re seeing here maybe the first fruits of good EMR design, and it’s a prod for surgeons to look into EMR design and ask whether we can design EMR notes for vascular follow-up in the ER such that we pull good EMR data over great numbers of patients," he said at the annual meeting of the Midwestern Vascular Surgical Society.
Dr. Vogel said that the Cerner database is not as population based as Medicare, capturing observational patient EMR data on more than 84 million admissions and ambulatory visits at roughly 187 participating hospitals, albeit primarily urban. Cerner is the second largest EMR in the United States after Epic.
The analysis encompassed 1,458 elective first admissions with a diagnosis of peripheral artery disease (PAD) undergoing a lower-extremity procedure from October 2008 to December 2010. Of these, 777 had open surgery and 681 an endovascular procedure.
Intermittent claudication was the most common indication for any procedure, present in 56.2% of open and 43.8% of endovascular patients.
The overall readmission rate at 30 days was surprisingly high at 14.5%, and was also unexpectedly high for for those with claudication, at 10.2% in the open and 11.3% in the endovascular group, said Dr. Vogel, chief of vascular surgery at the University of Missouri Hospitals and Clinics, Columbia.
"The frightening number to think about is that, in the claudicant group, we have a 10% readmission rate within 30 days," he said, noting that rates were very similar between groups. "So that’s a number we should all begin to think about."
As expected, readmission rates in the open and endovascular groups increased with disease severity. Rates for rest pain and gangrene were 14% vs. 18.2%, and 22% vs. 24%, respectively.
In bivariate analysis, blacks were significantly more likely to be readmitted 30 days after discharge (odds ratio, 1.56), as were patients discharged to a skilled nursing facility or nursing home (OR, 2.59), he said.
There was a nonsignificant trend toward higher readmissions at teaching hospitals (OR, 1.20), while a hospital stay of more than 7 days was a strong, significant predictor of 30-day readmission (OR, 2.54).
Readmissions also were increased in patients with a Charlson Comorbidity Index score of 3-5 (OR, 1.56) or score of 6-10 (OR, 1.90), diabetes (OR, 1.41), or sepsis (OR, 2.99), he said.
The risk of 30-day readmission was increased more than fivefold among patients with poor liver function, as indicated by total bilirubin levels greater than 2 mg/dL (OR, 5.15) or AST over 100 U/L (OR, 5.56). Risk was also more than twofold higher among patients with renal disease, as indicated by hemoglobin (nadir) less than 8 g/dL (OR, 2.17) and serum creatinine of at least 2 mg/dL (OR, 2.07), as well as those dispensed a staggering 30 medications or more (OR, 2.63), Dr. Vogel reported.
Notably, patients with cardiac troponin levels above 0.2 mg/dL were not at significantly higher risk of readmission (OR, 1.75), although those with a white blood cell count greater than 15,000/mcL were (OR, 2.1), which goes along with the finding of sepsis, he said.
In multivariate logistic regression analysis adjusting for age, disease severity, and race, PAD severity dropped out but male gender (OR, 1.39), Charlson Comorbidity Index (OR 1.12), length of stay (OR, 1.25), AST (OR 2.89), and more than 30 dispensed medications (OR, 1.84) remained significant.
"I think these are the things we’re going to have to look at if we’re going to really address readmissions," Dr. Vogel said.
He highlighted a new algorithm created at the Dartmouth-Hitchcock Medical Center that describes strategies for both predicting and preventing readmissions in vascular surgery (J. Vasc. Surg. 2012 56:556-62).
"It’s fun to describe all this, but the next step is to create change," he added.
During a discussion of the study, Dr. Vogel said that it was possible to calculate specialty-specific readmission rates but that such an analysis had not been performed yet.
Society for Vascular Surgery (SVS) President Peter Gloviczki then rose from the audience to say that such an analysis is very important in light of a recent Medicare database analysis reporting that endovascular lower-extremity revascularization performed by vascular specialists results in higher costs, longer hospital stays, and more repeat revascularization procedures and amputations than the same procedure performed by interventional radiologists (J. Vasc. Interv. Radiol. 2012:23:3-9).
He went on to say that the controversial paper, which was sharply rebuked by past SVS President Richard Cambria, failed to define indications for the interventions or major vs. minor amputations.
"I think if your data show, not necessarily the outcome, but the case mix of the specialties and what we believe is the severity of disease that vascular surgeons take care of compared to radiologists, that would be very good because that is a way to answer with data, and not with rhetoric," Dr. Gloviczki said.
Dr. Vogel agreed that vascular surgeons, as a rule, treat sicker patients with heavier disease burden, subsequently leading to these various secondary outcomes, and that the Medicare analysis failed to adequately process the data.
"It was a very jaded view," he said.
Session comoderator Dr. Melina Kibbe, a vascular surgeon with Northwestern Memorial Hospital in Chicago, said that the current analysis is the first to use the Cerner database and "that this could be why we’re seeing different outcomes than what other people have reported because this is a more real-world database."
She went on to say that using lower-extremity readmissions as a quality measure is highly problematic because care of these patients, much like that for those with cancer, is often staged and extends for years.
Those thoughts were echoed by the newly elected president of the Midwestern Vascular Surgical Society, Dr. Timothy Kresowik. In an interview, he said, "I’d stay away from lower extremity to begin with. I think it’s just a terrible area to try to do performance measures, especially short-term performance measures, because the important thing to remember about lower-extremity bypass is the real issues are long term."
Dr. Vogel, Dr. Geraghty, Dr. Gloviczki, Dr. Kibbe, and Dr. Kresowik reported having no relevant conflicts of interest.
MILWAUKEE – Less invasive lower-extremity endovascular interventions do not reduce hospital readmissions among patients with peripheral artery disease, according to an analysis of the Cerner Health Facts database.
The 30-day readmission rate was 13.9% for patients who underwent open surgery and 15.3% for those who had an endovascular procedure.
Lead author Dr. Todd Vogel expressed surprise that the two approaches were relatively equal, adding that, "I thought with endo, we’re doing less, they’d come back more."
The common practice of staging lower-limb endovascular interventions is creating concerns that use of hospital readmissions as a quality outcome measure for reimbursement may not accurately identify planned readmissions or quality of care.
Session moderator Dr. Patrick Geraghty said in an interview that lower-extremity intervention outcomes "are probably the most complex and difficult to define outcomes issue for all of vascular surgery," as compared with carotid and aortic aneurysms, and that this is already reflected in efforts proposed by the National Surgical Quality Improvement Program (NSQIP) and the Centers for Medicare and Medicaid Services (CMS).
"Lower-extremity readmission is going to be a real hot-button discussion because we already know it’s substantial," he said. "If I do a stent graft for someone with leg ischemia and the flow improves and they go home on post-op day 1, and I bring them back 10 days later for a planned debridement of a toe ulcer that we’d been looking at, was that bad? Was that poor care, something I should be penalized for?
"Or was it just good care, but it didn’t fit into CMS’s box of everything should be done within one admission and that any readmission is therefore bad?"
The current analysis is unique in that utilizes electronic medical record (EMR) data to provide real-world outcomes for lower-limb interventions, said Dr. Geraghty, a vascular surgeon with Barnes-Jewish Hospital in St. Louis.
"I think we’re seeing here maybe the first fruits of good EMR design, and it’s a prod for surgeons to look into EMR design and ask whether we can design EMR notes for vascular follow-up in the ER such that we pull good EMR data over great numbers of patients," he said at the annual meeting of the Midwestern Vascular Surgical Society.
Dr. Vogel said that the Cerner database is not as population based as Medicare, capturing observational patient EMR data on more than 84 million admissions and ambulatory visits at roughly 187 participating hospitals, albeit primarily urban. Cerner is the second largest EMR in the United States after Epic.
The analysis encompassed 1,458 elective first admissions with a diagnosis of peripheral artery disease (PAD) undergoing a lower-extremity procedure from October 2008 to December 2010. Of these, 777 had open surgery and 681 an endovascular procedure.
Intermittent claudication was the most common indication for any procedure, present in 56.2% of open and 43.8% of endovascular patients.
The overall readmission rate at 30 days was surprisingly high at 14.5%, and was also unexpectedly high for for those with claudication, at 10.2% in the open and 11.3% in the endovascular group, said Dr. Vogel, chief of vascular surgery at the University of Missouri Hospitals and Clinics, Columbia.
"The frightening number to think about is that, in the claudicant group, we have a 10% readmission rate within 30 days," he said, noting that rates were very similar between groups. "So that’s a number we should all begin to think about."
As expected, readmission rates in the open and endovascular groups increased with disease severity. Rates for rest pain and gangrene were 14% vs. 18.2%, and 22% vs. 24%, respectively.
In bivariate analysis, blacks were significantly more likely to be readmitted 30 days after discharge (odds ratio, 1.56), as were patients discharged to a skilled nursing facility or nursing home (OR, 2.59), he said.
There was a nonsignificant trend toward higher readmissions at teaching hospitals (OR, 1.20), while a hospital stay of more than 7 days was a strong, significant predictor of 30-day readmission (OR, 2.54).
Readmissions also were increased in patients with a Charlson Comorbidity Index score of 3-5 (OR, 1.56) or score of 6-10 (OR, 1.90), diabetes (OR, 1.41), or sepsis (OR, 2.99), he said.
The risk of 30-day readmission was increased more than fivefold among patients with poor liver function, as indicated by total bilirubin levels greater than 2 mg/dL (OR, 5.15) or AST over 100 U/L (OR, 5.56). Risk was also more than twofold higher among patients with renal disease, as indicated by hemoglobin (nadir) less than 8 g/dL (OR, 2.17) and serum creatinine of at least 2 mg/dL (OR, 2.07), as well as those dispensed a staggering 30 medications or more (OR, 2.63), Dr. Vogel reported.
Notably, patients with cardiac troponin levels above 0.2 mg/dL were not at significantly higher risk of readmission (OR, 1.75), although those with a white blood cell count greater than 15,000/mcL were (OR, 2.1), which goes along with the finding of sepsis, he said.
In multivariate logistic regression analysis adjusting for age, disease severity, and race, PAD severity dropped out but male gender (OR, 1.39), Charlson Comorbidity Index (OR 1.12), length of stay (OR, 1.25), AST (OR 2.89), and more than 30 dispensed medications (OR, 1.84) remained significant.
"I think these are the things we’re going to have to look at if we’re going to really address readmissions," Dr. Vogel said.
He highlighted a new algorithm created at the Dartmouth-Hitchcock Medical Center that describes strategies for both predicting and preventing readmissions in vascular surgery (J. Vasc. Surg. 2012 56:556-62).
"It’s fun to describe all this, but the next step is to create change," he added.
During a discussion of the study, Dr. Vogel said that it was possible to calculate specialty-specific readmission rates but that such an analysis had not been performed yet.
Society for Vascular Surgery (SVS) President Peter Gloviczki then rose from the audience to say that such an analysis is very important in light of a recent Medicare database analysis reporting that endovascular lower-extremity revascularization performed by vascular specialists results in higher costs, longer hospital stays, and more repeat revascularization procedures and amputations than the same procedure performed by interventional radiologists (J. Vasc. Interv. Radiol. 2012:23:3-9).
He went on to say that the controversial paper, which was sharply rebuked by past SVS President Richard Cambria, failed to define indications for the interventions or major vs. minor amputations.
"I think if your data show, not necessarily the outcome, but the case mix of the specialties and what we believe is the severity of disease that vascular surgeons take care of compared to radiologists, that would be very good because that is a way to answer with data, and not with rhetoric," Dr. Gloviczki said.
Dr. Vogel agreed that vascular surgeons, as a rule, treat sicker patients with heavier disease burden, subsequently leading to these various secondary outcomes, and that the Medicare analysis failed to adequately process the data.
"It was a very jaded view," he said.
Session comoderator Dr. Melina Kibbe, a vascular surgeon with Northwestern Memorial Hospital in Chicago, said that the current analysis is the first to use the Cerner database and "that this could be why we’re seeing different outcomes than what other people have reported because this is a more real-world database."
She went on to say that using lower-extremity readmissions as a quality measure is highly problematic because care of these patients, much like that for those with cancer, is often staged and extends for years.
Those thoughts were echoed by the newly elected president of the Midwestern Vascular Surgical Society, Dr. Timothy Kresowik. In an interview, he said, "I’d stay away from lower extremity to begin with. I think it’s just a terrible area to try to do performance measures, especially short-term performance measures, because the important thing to remember about lower-extremity bypass is the real issues are long term."
Dr. Vogel, Dr. Geraghty, Dr. Gloviczki, Dr. Kibbe, and Dr. Kresowik reported having no relevant conflicts of interest.
MILWAUKEE – Less invasive lower-extremity endovascular interventions do not reduce hospital readmissions among patients with peripheral artery disease, according to an analysis of the Cerner Health Facts database.
The 30-day readmission rate was 13.9% for patients who underwent open surgery and 15.3% for those who had an endovascular procedure.
Lead author Dr. Todd Vogel expressed surprise that the two approaches were relatively equal, adding that, "I thought with endo, we’re doing less, they’d come back more."
The common practice of staging lower-limb endovascular interventions is creating concerns that use of hospital readmissions as a quality outcome measure for reimbursement may not accurately identify planned readmissions or quality of care.
Session moderator Dr. Patrick Geraghty said in an interview that lower-extremity intervention outcomes "are probably the most complex and difficult to define outcomes issue for all of vascular surgery," as compared with carotid and aortic aneurysms, and that this is already reflected in efforts proposed by the National Surgical Quality Improvement Program (NSQIP) and the Centers for Medicare and Medicaid Services (CMS).
"Lower-extremity readmission is going to be a real hot-button discussion because we already know it’s substantial," he said. "If I do a stent graft for someone with leg ischemia and the flow improves and they go home on post-op day 1, and I bring them back 10 days later for a planned debridement of a toe ulcer that we’d been looking at, was that bad? Was that poor care, something I should be penalized for?
"Or was it just good care, but it didn’t fit into CMS’s box of everything should be done within one admission and that any readmission is therefore bad?"
The current analysis is unique in that utilizes electronic medical record (EMR) data to provide real-world outcomes for lower-limb interventions, said Dr. Geraghty, a vascular surgeon with Barnes-Jewish Hospital in St. Louis.
"I think we’re seeing here maybe the first fruits of good EMR design, and it’s a prod for surgeons to look into EMR design and ask whether we can design EMR notes for vascular follow-up in the ER such that we pull good EMR data over great numbers of patients," he said at the annual meeting of the Midwestern Vascular Surgical Society.
Dr. Vogel said that the Cerner database is not as population based as Medicare, capturing observational patient EMR data on more than 84 million admissions and ambulatory visits at roughly 187 participating hospitals, albeit primarily urban. Cerner is the second largest EMR in the United States after Epic.
The analysis encompassed 1,458 elective first admissions with a diagnosis of peripheral artery disease (PAD) undergoing a lower-extremity procedure from October 2008 to December 2010. Of these, 777 had open surgery and 681 an endovascular procedure.
Intermittent claudication was the most common indication for any procedure, present in 56.2% of open and 43.8% of endovascular patients.
The overall readmission rate at 30 days was surprisingly high at 14.5%, and was also unexpectedly high for for those with claudication, at 10.2% in the open and 11.3% in the endovascular group, said Dr. Vogel, chief of vascular surgery at the University of Missouri Hospitals and Clinics, Columbia.
"The frightening number to think about is that, in the claudicant group, we have a 10% readmission rate within 30 days," he said, noting that rates were very similar between groups. "So that’s a number we should all begin to think about."
As expected, readmission rates in the open and endovascular groups increased with disease severity. Rates for rest pain and gangrene were 14% vs. 18.2%, and 22% vs. 24%, respectively.
In bivariate analysis, blacks were significantly more likely to be readmitted 30 days after discharge (odds ratio, 1.56), as were patients discharged to a skilled nursing facility or nursing home (OR, 2.59), he said.
There was a nonsignificant trend toward higher readmissions at teaching hospitals (OR, 1.20), while a hospital stay of more than 7 days was a strong, significant predictor of 30-day readmission (OR, 2.54).
Readmissions also were increased in patients with a Charlson Comorbidity Index score of 3-5 (OR, 1.56) or score of 6-10 (OR, 1.90), diabetes (OR, 1.41), or sepsis (OR, 2.99), he said.
The risk of 30-day readmission was increased more than fivefold among patients with poor liver function, as indicated by total bilirubin levels greater than 2 mg/dL (OR, 5.15) or AST over 100 U/L (OR, 5.56). Risk was also more than twofold higher among patients with renal disease, as indicated by hemoglobin (nadir) less than 8 g/dL (OR, 2.17) and serum creatinine of at least 2 mg/dL (OR, 2.07), as well as those dispensed a staggering 30 medications or more (OR, 2.63), Dr. Vogel reported.
Notably, patients with cardiac troponin levels above 0.2 mg/dL were not at significantly higher risk of readmission (OR, 1.75), although those with a white blood cell count greater than 15,000/mcL were (OR, 2.1), which goes along with the finding of sepsis, he said.
In multivariate logistic regression analysis adjusting for age, disease severity, and race, PAD severity dropped out but male gender (OR, 1.39), Charlson Comorbidity Index (OR 1.12), length of stay (OR, 1.25), AST (OR 2.89), and more than 30 dispensed medications (OR, 1.84) remained significant.
"I think these are the things we’re going to have to look at if we’re going to really address readmissions," Dr. Vogel said.
He highlighted a new algorithm created at the Dartmouth-Hitchcock Medical Center that describes strategies for both predicting and preventing readmissions in vascular surgery (J. Vasc. Surg. 2012 56:556-62).
"It’s fun to describe all this, but the next step is to create change," he added.
During a discussion of the study, Dr. Vogel said that it was possible to calculate specialty-specific readmission rates but that such an analysis had not been performed yet.
Society for Vascular Surgery (SVS) President Peter Gloviczki then rose from the audience to say that such an analysis is very important in light of a recent Medicare database analysis reporting that endovascular lower-extremity revascularization performed by vascular specialists results in higher costs, longer hospital stays, and more repeat revascularization procedures and amputations than the same procedure performed by interventional radiologists (J. Vasc. Interv. Radiol. 2012:23:3-9).
He went on to say that the controversial paper, which was sharply rebuked by past SVS President Richard Cambria, failed to define indications for the interventions or major vs. minor amputations.
"I think if your data show, not necessarily the outcome, but the case mix of the specialties and what we believe is the severity of disease that vascular surgeons take care of compared to radiologists, that would be very good because that is a way to answer with data, and not with rhetoric," Dr. Gloviczki said.
Dr. Vogel agreed that vascular surgeons, as a rule, treat sicker patients with heavier disease burden, subsequently leading to these various secondary outcomes, and that the Medicare analysis failed to adequately process the data.
"It was a very jaded view," he said.
Session comoderator Dr. Melina Kibbe, a vascular surgeon with Northwestern Memorial Hospital in Chicago, said that the current analysis is the first to use the Cerner database and "that this could be why we’re seeing different outcomes than what other people have reported because this is a more real-world database."
She went on to say that using lower-extremity readmissions as a quality measure is highly problematic because care of these patients, much like that for those with cancer, is often staged and extends for years.
Those thoughts were echoed by the newly elected president of the Midwestern Vascular Surgical Society, Dr. Timothy Kresowik. In an interview, he said, "I’d stay away from lower extremity to begin with. I think it’s just a terrible area to try to do performance measures, especially short-term performance measures, because the important thing to remember about lower-extremity bypass is the real issues are long term."
Dr. Vogel, Dr. Geraghty, Dr. Gloviczki, Dr. Kibbe, and Dr. Kresowik reported having no relevant conflicts of interest.
AT THE ANNUAL MEETING OF THE MIDWESTERN VASCULAR SURGICAL SOCIETY
Major Finding: The 30-day readmission rate was 13.9% for open surgery and 15.3% for an endovascular procedure.
Data Source: The electronic medical record analysis included 1,458 elective index admissions with a diagnosis of peripheral artery disease undergoing a lower-extremity procedure from October 2008 to December 2010.
Disclosures: Dr. Vogel, Dr. Geraghty, Dr. Gloviczki, Dr. Kibbe, and Dr. Kresowik reported no relevant conflicts of interest.
Carotid-Artery Stenting May Fall to 65
MILWAUKEE – The risk for worse outcomes following carotid-artery stenting may extend to even younger Medicare-age patients than previously reported by such pivotal trials as CREST, a provocative population study suggests.
The rate of the composite primary end point of death, stroke, or cardiac complications was 5.2% for carotid angioplasty and stenting (CAS) and 3.6% for carotid endarterectomy (CEA) among patients younger than age 65 years, and was 6.3% vs. 4.5% among patients aged 65 years or older, who comprised 76% of the study cohort (both P values less than .0001).
Rates of the primary end point were similar between the carotid stenting and endarterectomy groups among asymptomatic patients aged 65 years or older (4.1% vs. 3.8%; P = .25), but were significantly higher in symptomatic patients age 65 years or older who received stenting (22.5% vs. 12.5%; P less than .0001).
This finding was driven by significantly higher rates of all three individual components of the primary end point: death (5.1% vs. 2.2%), stroke (12.5% vs. 7.6%), and cardiac complications (7.5% v s. 4.2%), "which is a little bit different than what we thought, compared with the CREST trial," lead author Dr. Jeffrey Jim said at the annual Midwestern Vascular Surgical Society meeting.
In the lead-in phase of CREST (Carotid Revascularization Endarterectomy vs. Stent Trial), octogenarians were found to be at higher risk of in-hospital death and stroke post CAS, but not myocardial infarction (J. Vasc. Surg. 2004;40:1106-11).
Subsequent CREST analyses have identified an interaction between age and carotid stenting efficacy, with the crossover at an age of approximately 70 years (N. Engl. J. Med. 2010;363:11-23).
The current results appear to move that threshold to an even younger age, just as the Centers for Medicare and Medicaid Services starts reconsidering the national coverage decision for carotid-artery stenting. Although he did not present the data, Dr. Jim noted that hospital costs also were higher for stenting patients.
"Our results show that carotid angioplasty and stenting was associated with a higher rate of adverse outcomes and increased charges among patients of Medicare age, and really don’t support the widespread use of carotid stenting over CEA in this general population," Dr. Jim said.
Session moderator Dr. Patrick Geraghty, a vascular surgeon with Barnes–Jewish Health in St. Louis, said the difference in MI rates between arms "basically turns the CREST findings on their head," and asked whether cardiac troponin levels were tracked equally in both arms.
Dr. Jim responded that such tracking wasn’t possible with the Nationwide Inpatient Sample (NIS) database used for the analysis, and that it’s unknown whether one hospital called a troponin level of 0.15 ng/mL a troponin leak, while another coded that as an MI. Anatomic information and operative details also were not available.
The analysis was based on 678,081 hospitalizations for CEA and CAS from 2005 to 2009, the latest available data in the NIS, a comprehensive, inpatient database developed as part of the Healthcare Cost and Utilization Project and designed to approximate a 20% sample of U.S. hospitals.
The 595,813 CEA patients were more likely to be asymptomatic, whereas the 82,268 CAS patients were more likely to be male, medically high risk, treated at a teaching hospital, and an emergent/urgent admission.
The average age was 71 years in the CEA group and 70 years in the CAS group. Three-fourths of both groups had Medicare insurance coverage.
In the entire study cohort, the composite primary end point occurred in 6% of the carotid stenting group and 4.3% of the endarterectomy group (P less than .0001), said Dr. Jim, a vascular specialist at Washington University School of Medicine, St. Louis.
Patients who underwent carotid stenting experienced significantly higher rates of each individual component of the primary end point: death (1.1% vs. 0.5%), stroke (2% vs. 1%) and cardiac complications (3.6% vs. 3.1%).
Independent predictors of the primary end point were CAS, symptomatic stenosis, and medical high risk, defined as a patient age 80 years or older, or a patient who had renal failure, severe chronic lung disease, recent MI, coronary bypass/valve surgery within 30 days, unstable angina, or class III/IV heart failure.
Dr. Jim and Dr. Geraghty reported having no relevant conflicts of interest.
MILWAUKEE – The risk for worse outcomes following carotid-artery stenting may extend to even younger Medicare-age patients than previously reported by such pivotal trials as CREST, a provocative population study suggests.
The rate of the composite primary end point of death, stroke, or cardiac complications was 5.2% for carotid angioplasty and stenting (CAS) and 3.6% for carotid endarterectomy (CEA) among patients younger than age 65 years, and was 6.3% vs. 4.5% among patients aged 65 years or older, who comprised 76% of the study cohort (both P values less than .0001).
Rates of the primary end point were similar between the carotid stenting and endarterectomy groups among asymptomatic patients aged 65 years or older (4.1% vs. 3.8%; P = .25), but were significantly higher in symptomatic patients age 65 years or older who received stenting (22.5% vs. 12.5%; P less than .0001).
This finding was driven by significantly higher rates of all three individual components of the primary end point: death (5.1% vs. 2.2%), stroke (12.5% vs. 7.6%), and cardiac complications (7.5% v s. 4.2%), "which is a little bit different than what we thought, compared with the CREST trial," lead author Dr. Jeffrey Jim said at the annual Midwestern Vascular Surgical Society meeting.
In the lead-in phase of CREST (Carotid Revascularization Endarterectomy vs. Stent Trial), octogenarians were found to be at higher risk of in-hospital death and stroke post CAS, but not myocardial infarction (J. Vasc. Surg. 2004;40:1106-11).
Subsequent CREST analyses have identified an interaction between age and carotid stenting efficacy, with the crossover at an age of approximately 70 years (N. Engl. J. Med. 2010;363:11-23).
The current results appear to move that threshold to an even younger age, just as the Centers for Medicare and Medicaid Services starts reconsidering the national coverage decision for carotid-artery stenting. Although he did not present the data, Dr. Jim noted that hospital costs also were higher for stenting patients.
"Our results show that carotid angioplasty and stenting was associated with a higher rate of adverse outcomes and increased charges among patients of Medicare age, and really don’t support the widespread use of carotid stenting over CEA in this general population," Dr. Jim said.
Session moderator Dr. Patrick Geraghty, a vascular surgeon with Barnes–Jewish Health in St. Louis, said the difference in MI rates between arms "basically turns the CREST findings on their head," and asked whether cardiac troponin levels were tracked equally in both arms.
Dr. Jim responded that such tracking wasn’t possible with the Nationwide Inpatient Sample (NIS) database used for the analysis, and that it’s unknown whether one hospital called a troponin level of 0.15 ng/mL a troponin leak, while another coded that as an MI. Anatomic information and operative details also were not available.
The analysis was based on 678,081 hospitalizations for CEA and CAS from 2005 to 2009, the latest available data in the NIS, a comprehensive, inpatient database developed as part of the Healthcare Cost and Utilization Project and designed to approximate a 20% sample of U.S. hospitals.
The 595,813 CEA patients were more likely to be asymptomatic, whereas the 82,268 CAS patients were more likely to be male, medically high risk, treated at a teaching hospital, and an emergent/urgent admission.
The average age was 71 years in the CEA group and 70 years in the CAS group. Three-fourths of both groups had Medicare insurance coverage.
In the entire study cohort, the composite primary end point occurred in 6% of the carotid stenting group and 4.3% of the endarterectomy group (P less than .0001), said Dr. Jim, a vascular specialist at Washington University School of Medicine, St. Louis.
Patients who underwent carotid stenting experienced significantly higher rates of each individual component of the primary end point: death (1.1% vs. 0.5%), stroke (2% vs. 1%) and cardiac complications (3.6% vs. 3.1%).
Independent predictors of the primary end point were CAS, symptomatic stenosis, and medical high risk, defined as a patient age 80 years or older, or a patient who had renal failure, severe chronic lung disease, recent MI, coronary bypass/valve surgery within 30 days, unstable angina, or class III/IV heart failure.
Dr. Jim and Dr. Geraghty reported having no relevant conflicts of interest.
MILWAUKEE – The risk for worse outcomes following carotid-artery stenting may extend to even younger Medicare-age patients than previously reported by such pivotal trials as CREST, a provocative population study suggests.
The rate of the composite primary end point of death, stroke, or cardiac complications was 5.2% for carotid angioplasty and stenting (CAS) and 3.6% for carotid endarterectomy (CEA) among patients younger than age 65 years, and was 6.3% vs. 4.5% among patients aged 65 years or older, who comprised 76% of the study cohort (both P values less than .0001).
Rates of the primary end point were similar between the carotid stenting and endarterectomy groups among asymptomatic patients aged 65 years or older (4.1% vs. 3.8%; P = .25), but were significantly higher in symptomatic patients age 65 years or older who received stenting (22.5% vs. 12.5%; P less than .0001).
This finding was driven by significantly higher rates of all three individual components of the primary end point: death (5.1% vs. 2.2%), stroke (12.5% vs. 7.6%), and cardiac complications (7.5% v s. 4.2%), "which is a little bit different than what we thought, compared with the CREST trial," lead author Dr. Jeffrey Jim said at the annual Midwestern Vascular Surgical Society meeting.
In the lead-in phase of CREST (Carotid Revascularization Endarterectomy vs. Stent Trial), octogenarians were found to be at higher risk of in-hospital death and stroke post CAS, but not myocardial infarction (J. Vasc. Surg. 2004;40:1106-11).
Subsequent CREST analyses have identified an interaction between age and carotid stenting efficacy, with the crossover at an age of approximately 70 years (N. Engl. J. Med. 2010;363:11-23).
The current results appear to move that threshold to an even younger age, just as the Centers for Medicare and Medicaid Services starts reconsidering the national coverage decision for carotid-artery stenting. Although he did not present the data, Dr. Jim noted that hospital costs also were higher for stenting patients.
"Our results show that carotid angioplasty and stenting was associated with a higher rate of adverse outcomes and increased charges among patients of Medicare age, and really don’t support the widespread use of carotid stenting over CEA in this general population," Dr. Jim said.
Session moderator Dr. Patrick Geraghty, a vascular surgeon with Barnes–Jewish Health in St. Louis, said the difference in MI rates between arms "basically turns the CREST findings on their head," and asked whether cardiac troponin levels were tracked equally in both arms.
Dr. Jim responded that such tracking wasn’t possible with the Nationwide Inpatient Sample (NIS) database used for the analysis, and that it’s unknown whether one hospital called a troponin level of 0.15 ng/mL a troponin leak, while another coded that as an MI. Anatomic information and operative details also were not available.
The analysis was based on 678,081 hospitalizations for CEA and CAS from 2005 to 2009, the latest available data in the NIS, a comprehensive, inpatient database developed as part of the Healthcare Cost and Utilization Project and designed to approximate a 20% sample of U.S. hospitals.
The 595,813 CEA patients were more likely to be asymptomatic, whereas the 82,268 CAS patients were more likely to be male, medically high risk, treated at a teaching hospital, and an emergent/urgent admission.
The average age was 71 years in the CEA group and 70 years in the CAS group. Three-fourths of both groups had Medicare insurance coverage.
In the entire study cohort, the composite primary end point occurred in 6% of the carotid stenting group and 4.3% of the endarterectomy group (P less than .0001), said Dr. Jim, a vascular specialist at Washington University School of Medicine, St. Louis.
Patients who underwent carotid stenting experienced significantly higher rates of each individual component of the primary end point: death (1.1% vs. 0.5%), stroke (2% vs. 1%) and cardiac complications (3.6% vs. 3.1%).
Independent predictors of the primary end point were CAS, symptomatic stenosis, and medical high risk, defined as a patient age 80 years or older, or a patient who had renal failure, severe chronic lung disease, recent MI, coronary bypass/valve surgery within 30 days, unstable angina, or class III/IV heart failure.
Dr. Jim and Dr. Geraghty reported having no relevant conflicts of interest.
AT THE ANNUAL MIDWESTERN VASCULAR SURGICAL SOCIETY MEETING
Major Finding: The rate of the primary end point of death, stroke, or cardiac complications was 5.2% for carotid angioplasty and stenting vs. 3.6 for carotid endarterectomy among patients younger than 65 years, and 6.3% vs. 4.5% among those 65 or older (both P values less than .0001).
Data Source: A population-based study of 678,081 hospitalizations for carotid stenting or endarterectomy, stratified by Medicare age, in the Nationwide Inpatient Sample.
Disclosures: Dr. Jim and Dr. Geraghty reported no relevant conflicts of interest.
GRACE: Insulin Glargine Fails to Halt Atherosclerosis Progression
MUNICH – Insulin glargine and omega-3 fatty acids failed to retard carotid atherosclerosis progression in patients with diabetes or prediabetes at high cardiovascular risk in the GRACE trial.
Compared with standard glycemic care, insulin glargine provided a nonsignificant difference of –0.0030 mm/year in the primary end point of rate of change in maximum carotid intima media thickness (CIMT) at 12 carotid sites.
For the secondary outcomes, which included four segments of the common carotid artery and eight segments of the common carotid and bifurcation sites, the long-acting basal insulin resulted in slight but statistically significant annualized differences in maximum CIMT of –0.0033 mm/year and –0.0045 mm/year, respectively.
"Although not conclusive, our study suggests a beneficial effect of insulin glargine on vascular disease progression," Dr. Eva Lonn said at the annual congress of the European Society of Cardiology. "These findings raise the possibility that longer term treatment might result in cardiovascular event reduction."
This hypothesis is currently under evaluation in extended follow-up of ORIGIN (Outcome Reduction With an Initial Glargine Intervention), the parent trial of GRACE (Glucose Reduction and Atherosclerosis Continuing Evaluation).
With regard to omega-3 fatty acids, no significant differences were observed for the primary outcome (difference 0.0009 mm/yr), or the secondary outcomes in the common carotid (–0.0004 mm/yr) and common carotid and bifurcation sites (0.0022 mm/year), reported Dr. Lonn, professor of medicine at McMaster University and director of the vascular research ultrasound laboratory at the Population Health Research Institute, both in Hamilton, Ontario.
Given the neutral effect of omega-3 fatty acids, the focus in diabetes should be on proven therapies such as lipid-lowering and blood pressure–lowering drugs and glycemic control, she said in an interview. There is no harm, however, should patients wish to take the supplements.
Discussant John E. Deanfield said there was no evidence of benefit or harm from either treatment, and pointed out that the results of GRACE are concordant with those reported from the larger ORIGIN trial.
In that trial, insulin glargine reduced the risk of developing type 2 diabetes by 28% among patients with prediabetes, but had a neutral effect on cardiovascular outcomes (N. Engl. J. Med. 2012;367:319-28). Omega-3 fatty acids reduced triglyceride levels, but also failed to reduce the rate of cardiovascular events (N. Engl. J. Med. 2012;367:309-18).
After a median clinical follow up of 6.2 years in GRACE, Dr. Lonn reported that rates of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke were similar between the insulin glargine and standard care groups (18.6% vs. 16.9%), as was all-cause mortality (17.1% vs. 17.4%).
Dr. Deanfield said the lack of benefit from either treatment was disappointing and suggested the GRACE authors might have been better served by choosing the common carotid segment as their primary outcome, rather than one of their secondary outcomes.
He also noted that there is controversy over whether IMT itself is the best measure of structural arterial disease, with a recent meta-analysis demonstrating a lack of relationship between progression of CIMT and hazard for cardiovascular events (Lancet 2012;379:2053-62).
"Finally, the reporting strategy for IMT in this trial – which shows the change in IMT levels over 5 years without giving us, as yet, the baseline absolute levels of IMT – is interesting and might be missing a trick in terms of our understanding of this signal," said Dr. Deanfield, professor of cardiology at University College London.
A total of 1,184 patients recruited from 32 centers in seven countries received open-label insulin glargine injection or standard glycemic care, and double-blinded therapy with a 1-g/day omega-3 supplement containing eicosapentaenoic acid 465 mg plus docosahexaenoic acid 375 mg or matching placebo.
Patients had to be at least 50 years old (mean age 63 years) and have prediabetes or newly diagnosed type 2 diabetes or early type 2 diabetes, and be at high cardiovascular risk.
At baseline, 49% had a history of cardiovascular disease, 80% had hypertension, 60% had hyperlipidemia and 10% were current smokers. CIMT efficacy results were based on 1,091 patients with at least one adequate carotid ultrasound. Median follow-up from baseline to last CIMT scan was 5 years.
Insulin glargine was well tolerated and safe, with the most common reasons for discontinuation being patient preference in 76 patients and hypoglycemia in 9, Dr. Lonn said.
The study was funded by Sanofi; omega-3 fatty acid supplements and matching placebo were provided by Pronova BioPharma. Dr. Lonn reported research grants, lecture fees, and/or consulting fees from Astra-Zeneca, Canadian Institutes of Health Research, GlaxoSmithKline, Heart and Stroke Foundation of Canada, Merck, Novartis, Servier, and Sanofi. Dr. Deanfield reported consulting and speakers bureau participation for Pfizer, Merck, Roche, Takeda, Novartis, Sanofi, and Danone.
MUNICH – Insulin glargine and omega-3 fatty acids failed to retard carotid atherosclerosis progression in patients with diabetes or prediabetes at high cardiovascular risk in the GRACE trial.
Compared with standard glycemic care, insulin glargine provided a nonsignificant difference of –0.0030 mm/year in the primary end point of rate of change in maximum carotid intima media thickness (CIMT) at 12 carotid sites.
For the secondary outcomes, which included four segments of the common carotid artery and eight segments of the common carotid and bifurcation sites, the long-acting basal insulin resulted in slight but statistically significant annualized differences in maximum CIMT of –0.0033 mm/year and –0.0045 mm/year, respectively.
"Although not conclusive, our study suggests a beneficial effect of insulin glargine on vascular disease progression," Dr. Eva Lonn said at the annual congress of the European Society of Cardiology. "These findings raise the possibility that longer term treatment might result in cardiovascular event reduction."
This hypothesis is currently under evaluation in extended follow-up of ORIGIN (Outcome Reduction With an Initial Glargine Intervention), the parent trial of GRACE (Glucose Reduction and Atherosclerosis Continuing Evaluation).
With regard to omega-3 fatty acids, no significant differences were observed for the primary outcome (difference 0.0009 mm/yr), or the secondary outcomes in the common carotid (–0.0004 mm/yr) and common carotid and bifurcation sites (0.0022 mm/year), reported Dr. Lonn, professor of medicine at McMaster University and director of the vascular research ultrasound laboratory at the Population Health Research Institute, both in Hamilton, Ontario.
Given the neutral effect of omega-3 fatty acids, the focus in diabetes should be on proven therapies such as lipid-lowering and blood pressure–lowering drugs and glycemic control, she said in an interview. There is no harm, however, should patients wish to take the supplements.
Discussant John E. Deanfield said there was no evidence of benefit or harm from either treatment, and pointed out that the results of GRACE are concordant with those reported from the larger ORIGIN trial.
In that trial, insulin glargine reduced the risk of developing type 2 diabetes by 28% among patients with prediabetes, but had a neutral effect on cardiovascular outcomes (N. Engl. J. Med. 2012;367:319-28). Omega-3 fatty acids reduced triglyceride levels, but also failed to reduce the rate of cardiovascular events (N. Engl. J. Med. 2012;367:309-18).
After a median clinical follow up of 6.2 years in GRACE, Dr. Lonn reported that rates of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke were similar between the insulin glargine and standard care groups (18.6% vs. 16.9%), as was all-cause mortality (17.1% vs. 17.4%).
Dr. Deanfield said the lack of benefit from either treatment was disappointing and suggested the GRACE authors might have been better served by choosing the common carotid segment as their primary outcome, rather than one of their secondary outcomes.
He also noted that there is controversy over whether IMT itself is the best measure of structural arterial disease, with a recent meta-analysis demonstrating a lack of relationship between progression of CIMT and hazard for cardiovascular events (Lancet 2012;379:2053-62).
"Finally, the reporting strategy for IMT in this trial – which shows the change in IMT levels over 5 years without giving us, as yet, the baseline absolute levels of IMT – is interesting and might be missing a trick in terms of our understanding of this signal," said Dr. Deanfield, professor of cardiology at University College London.
A total of 1,184 patients recruited from 32 centers in seven countries received open-label insulin glargine injection or standard glycemic care, and double-blinded therapy with a 1-g/day omega-3 supplement containing eicosapentaenoic acid 465 mg plus docosahexaenoic acid 375 mg or matching placebo.
Patients had to be at least 50 years old (mean age 63 years) and have prediabetes or newly diagnosed type 2 diabetes or early type 2 diabetes, and be at high cardiovascular risk.
At baseline, 49% had a history of cardiovascular disease, 80% had hypertension, 60% had hyperlipidemia and 10% were current smokers. CIMT efficacy results were based on 1,091 patients with at least one adequate carotid ultrasound. Median follow-up from baseline to last CIMT scan was 5 years.
Insulin glargine was well tolerated and safe, with the most common reasons for discontinuation being patient preference in 76 patients and hypoglycemia in 9, Dr. Lonn said.
The study was funded by Sanofi; omega-3 fatty acid supplements and matching placebo were provided by Pronova BioPharma. Dr. Lonn reported research grants, lecture fees, and/or consulting fees from Astra-Zeneca, Canadian Institutes of Health Research, GlaxoSmithKline, Heart and Stroke Foundation of Canada, Merck, Novartis, Servier, and Sanofi. Dr. Deanfield reported consulting and speakers bureau participation for Pfizer, Merck, Roche, Takeda, Novartis, Sanofi, and Danone.
MUNICH – Insulin glargine and omega-3 fatty acids failed to retard carotid atherosclerosis progression in patients with diabetes or prediabetes at high cardiovascular risk in the GRACE trial.
Compared with standard glycemic care, insulin glargine provided a nonsignificant difference of –0.0030 mm/year in the primary end point of rate of change in maximum carotid intima media thickness (CIMT) at 12 carotid sites.
For the secondary outcomes, which included four segments of the common carotid artery and eight segments of the common carotid and bifurcation sites, the long-acting basal insulin resulted in slight but statistically significant annualized differences in maximum CIMT of –0.0033 mm/year and –0.0045 mm/year, respectively.
"Although not conclusive, our study suggests a beneficial effect of insulin glargine on vascular disease progression," Dr. Eva Lonn said at the annual congress of the European Society of Cardiology. "These findings raise the possibility that longer term treatment might result in cardiovascular event reduction."
This hypothesis is currently under evaluation in extended follow-up of ORIGIN (Outcome Reduction With an Initial Glargine Intervention), the parent trial of GRACE (Glucose Reduction and Atherosclerosis Continuing Evaluation).
With regard to omega-3 fatty acids, no significant differences were observed for the primary outcome (difference 0.0009 mm/yr), or the secondary outcomes in the common carotid (–0.0004 mm/yr) and common carotid and bifurcation sites (0.0022 mm/year), reported Dr. Lonn, professor of medicine at McMaster University and director of the vascular research ultrasound laboratory at the Population Health Research Institute, both in Hamilton, Ontario.
Given the neutral effect of omega-3 fatty acids, the focus in diabetes should be on proven therapies such as lipid-lowering and blood pressure–lowering drugs and glycemic control, she said in an interview. There is no harm, however, should patients wish to take the supplements.
Discussant John E. Deanfield said there was no evidence of benefit or harm from either treatment, and pointed out that the results of GRACE are concordant with those reported from the larger ORIGIN trial.
In that trial, insulin glargine reduced the risk of developing type 2 diabetes by 28% among patients with prediabetes, but had a neutral effect on cardiovascular outcomes (N. Engl. J. Med. 2012;367:319-28). Omega-3 fatty acids reduced triglyceride levels, but also failed to reduce the rate of cardiovascular events (N. Engl. J. Med. 2012;367:309-18).
After a median clinical follow up of 6.2 years in GRACE, Dr. Lonn reported that rates of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke were similar between the insulin glargine and standard care groups (18.6% vs. 16.9%), as was all-cause mortality (17.1% vs. 17.4%).
Dr. Deanfield said the lack of benefit from either treatment was disappointing and suggested the GRACE authors might have been better served by choosing the common carotid segment as their primary outcome, rather than one of their secondary outcomes.
He also noted that there is controversy over whether IMT itself is the best measure of structural arterial disease, with a recent meta-analysis demonstrating a lack of relationship between progression of CIMT and hazard for cardiovascular events (Lancet 2012;379:2053-62).
"Finally, the reporting strategy for IMT in this trial – which shows the change in IMT levels over 5 years without giving us, as yet, the baseline absolute levels of IMT – is interesting and might be missing a trick in terms of our understanding of this signal," said Dr. Deanfield, professor of cardiology at University College London.
A total of 1,184 patients recruited from 32 centers in seven countries received open-label insulin glargine injection or standard glycemic care, and double-blinded therapy with a 1-g/day omega-3 supplement containing eicosapentaenoic acid 465 mg plus docosahexaenoic acid 375 mg or matching placebo.
Patients had to be at least 50 years old (mean age 63 years) and have prediabetes or newly diagnosed type 2 diabetes or early type 2 diabetes, and be at high cardiovascular risk.
At baseline, 49% had a history of cardiovascular disease, 80% had hypertension, 60% had hyperlipidemia and 10% were current smokers. CIMT efficacy results were based on 1,091 patients with at least one adequate carotid ultrasound. Median follow-up from baseline to last CIMT scan was 5 years.
Insulin glargine was well tolerated and safe, with the most common reasons for discontinuation being patient preference in 76 patients and hypoglycemia in 9, Dr. Lonn said.
The study was funded by Sanofi; omega-3 fatty acid supplements and matching placebo were provided by Pronova BioPharma. Dr. Lonn reported research grants, lecture fees, and/or consulting fees from Astra-Zeneca, Canadian Institutes of Health Research, GlaxoSmithKline, Heart and Stroke Foundation of Canada, Merck, Novartis, Servier, and Sanofi. Dr. Deanfield reported consulting and speakers bureau participation for Pfizer, Merck, Roche, Takeda, Novartis, Sanofi, and Danone.
AT THE ANNUAL CONGRESS OF THE EUROPEAN SOCIETY OF CARDIOLOGY
Major Finding: The rate of change in maximum carotid intima media thickness at 12 carotid sites was not significantly different between insulin glargine (difference, –0.003 mm/yr) or omega-3 fatty acids (difference 0.0009 mm/yr) and standard glycemic control.
Data Source: GRACE, a substudy of 1,184 patients in the ORIGIN trial with dysglycemia and at high cardiovascular risk.
Disclosures: The study was funded by Sanofi; omega-3 fatty acid supplements and matching placebo were provided by Pronova BioPharma. Dr. Lonn reported research grants, lecture fees, and/or consulting fees from Astra-Zeneca, Canadian Institutes of Health Research, GlaxoSmithKline, Heart and Stroke Foundation of Canada, Merck, Novartis, Servier, and Sanofi. Dr. Deanfield reported consulting and speakers bureau participation for Pfizer, Merck, Roche, Takeda, Novartis, Sanofi, and Danone.
Pregnancy in Lupus Poses Unique Challenges
CHICAGO – The risk of active disease in pregnant women with systemic lupus erythematosus far outweighs the risks of most medications.
Indeed, the risk of pregnancy loss doubles if lupus is active during pregnancy and jumps fourfold if the autoimmune disease is active in the 3 months before conception.
"My general rule is that the inflammation of active lupus is more dangerous to a pregnancy than medications," said Dr. Megan Clowse, director of the Duke University Autoimmunity in Pregnancy Registry in Durham, N.C. "We don’t have a medication that will cause a 40% pregnancy loss. So I think it’s important to continue medications within this population, although some drugs are certainly better than others."
She advocates the use of hydroxychloroquine (Plaquenil) as the best way to prevent a systemic lupus erythematosus (SLE) flare. It’s a pregnancy category C drug because of reports of hearing abnormalities in children exposed to high doses of chloroquine (Aralen), but there are no clear fetal risks with hydroxychloroquine itself, particularly at the doses used by rheumatologists, she said. Moreover, several reports have suggested that hydroxychloroquine discontinuation during pregnancy may precipitate SLE flares, thereby worsening pregnancy prognosis.
The one exception to hydroxychloroquine use in SLE is the patient who’s been off the drug for years and is no longer symptomatic but becomes pregnant. "I don’t force those women back on their hydroxychloroquine, but basically everybody else should be on it," Dr. Clowse said at a symposium sponsored by the American College of Rheumatology.
For women with more active SLE, consider the use of azathioprine (Azasan, Imuran). It is a pregnancy category D drug due to the risk for fetal immunosuppression at delivery, but its use in SLE pregnancy is supported by extensive data among renal transplant patients, who have a higher rate of prematurity than SLE patients.
Azathioprine is most effective in preventing SLE flare in pregnancy, but Dr. Clowse said she has not been as impressed with its ability to treat flares during pregnancy. In her own recent study, azathioprine did not prevent pregnancy loss, and was actually associated with higher rates of loss among women with high-activity SLE.
When SLE flares occur, they need to be treated promptly, she stressed. Prednisone is probably the most effective treatment, although intravenous immunoglobulin may be a reasonable option. Prednisone is metabolized by the placenta, allowing only 10% of the maternal dose to reach the fetus. In contrast, the fluorinated corticosteroid betamethasone (Betnesol injection) is not metabolized and is transferred to the fetus, so it should not be used during pregnancy. Prednisone may decrease birth weight and is associated with a modest, threefold increased risk for cleft lip and palate, but this is really a first-trimester risk, she noted.
Drugs to avoid in pregnancy include cyclophosphamide (Cytoxan), mycophenolate mofetil (CellCept), and belimumab (Benlysta). A review of 26 pregnancies in 18 renal transplant patients receiving mycophenolate reported that 11 ended in spontaneous abortions and 10 in preterm births, and there were 4 cases of congenital anomalies (Transplantation 2006;82:1698-702). Not only was the 26% birth defect rate staggering compared with the 3% seen in the general population, but three of the infants had microtia. This was not simply underdeveloped pinnae, but the ears were located in the wrong place on the head, resulting in the babies being deaf, Dr. Clowse warned.
Although teratogenicity has not been observed in animals on belimumab, GlaxoSmithKline recently launched a global Benlysta Pregnancy Registry to prospectively collect data on birth defects and other pregnancy outcomes from women receiving belimumab within the 4 months prior to and/or during pregnancy (telephone: 1-877-681-6296).
Dr. Clowse said she recently began putting most of her pregnant SLE patients on aspirin 81 mg/day to prevent preeclampsia. Data from high-risk, nonlupus patients suggest aspirin may decrease the risk of preterm birth, preeclampsia, maternal hypertension, and low-birth weight without increasing the risk of congenital anomalies or ductus arteriosus closure observed with regular aspirin.
"It also, to be honest, takes away that whole discussion of low anticardiolipin antibodies and what do you do," she added.
Pregnant women with SLE should be closely monitored by a rheumatologist and an obstetrician skilled in high-risk pregnancies. Key parameters to monitor are hypertension, particularly in the first trimester, as this can increase the risk of pregnancy loss, preterm birth, and preeclampsia by up to 40%; and proteinuria, which may rise modestly during pregnancy due to increased renal function. More than a doubling or a 1-g increase of proteinuria, however, should raise the alarm, Dr. Clowse said.
To achieve the best possible pregnancy outcome, women with SLE should be advised to avoid pregnancy when SLE is active. Dr. Clowse said it’s recently come to her attention that in North Carolina and other parts of the United States where abstinence-only education has been the law of the land for the past dozen years, this may mean having that first conversation about contraception with a patient already in her 20s.
"I think it’s really important that we address this with our rheumatology patients," she said.
Dr. Clowse said progesterone-only contraceptives are probably the safest method in SLE patients, with medroxyprogesterone injection (Depo-Provera) generally well tolerated, and the 3-year etonogestrel implant (Implanon) is better tolerated than the levonorgestrel implant (Norplant). She also advises her SLE patients to use barrier methods and to pick up levonorgestrel (Plan B One-Step) on the way home from the clinic to have on hand for emergencies.
Dr. Clowse reported consulting for UCB and receiving grant support from the Arthritis Foundation.
CHICAGO – The risk of active disease in pregnant women with systemic lupus erythematosus far outweighs the risks of most medications.
Indeed, the risk of pregnancy loss doubles if lupus is active during pregnancy and jumps fourfold if the autoimmune disease is active in the 3 months before conception.
"My general rule is that the inflammation of active lupus is more dangerous to a pregnancy than medications," said Dr. Megan Clowse, director of the Duke University Autoimmunity in Pregnancy Registry in Durham, N.C. "We don’t have a medication that will cause a 40% pregnancy loss. So I think it’s important to continue medications within this population, although some drugs are certainly better than others."
She advocates the use of hydroxychloroquine (Plaquenil) as the best way to prevent a systemic lupus erythematosus (SLE) flare. It’s a pregnancy category C drug because of reports of hearing abnormalities in children exposed to high doses of chloroquine (Aralen), but there are no clear fetal risks with hydroxychloroquine itself, particularly at the doses used by rheumatologists, she said. Moreover, several reports have suggested that hydroxychloroquine discontinuation during pregnancy may precipitate SLE flares, thereby worsening pregnancy prognosis.
The one exception to hydroxychloroquine use in SLE is the patient who’s been off the drug for years and is no longer symptomatic but becomes pregnant. "I don’t force those women back on their hydroxychloroquine, but basically everybody else should be on it," Dr. Clowse said at a symposium sponsored by the American College of Rheumatology.
For women with more active SLE, consider the use of azathioprine (Azasan, Imuran). It is a pregnancy category D drug due to the risk for fetal immunosuppression at delivery, but its use in SLE pregnancy is supported by extensive data among renal transplant patients, who have a higher rate of prematurity than SLE patients.
Azathioprine is most effective in preventing SLE flare in pregnancy, but Dr. Clowse said she has not been as impressed with its ability to treat flares during pregnancy. In her own recent study, azathioprine did not prevent pregnancy loss, and was actually associated with higher rates of loss among women with high-activity SLE.
When SLE flares occur, they need to be treated promptly, she stressed. Prednisone is probably the most effective treatment, although intravenous immunoglobulin may be a reasonable option. Prednisone is metabolized by the placenta, allowing only 10% of the maternal dose to reach the fetus. In contrast, the fluorinated corticosteroid betamethasone (Betnesol injection) is not metabolized and is transferred to the fetus, so it should not be used during pregnancy. Prednisone may decrease birth weight and is associated with a modest, threefold increased risk for cleft lip and palate, but this is really a first-trimester risk, she noted.
Drugs to avoid in pregnancy include cyclophosphamide (Cytoxan), mycophenolate mofetil (CellCept), and belimumab (Benlysta). A review of 26 pregnancies in 18 renal transplant patients receiving mycophenolate reported that 11 ended in spontaneous abortions and 10 in preterm births, and there were 4 cases of congenital anomalies (Transplantation 2006;82:1698-702). Not only was the 26% birth defect rate staggering compared with the 3% seen in the general population, but three of the infants had microtia. This was not simply underdeveloped pinnae, but the ears were located in the wrong place on the head, resulting in the babies being deaf, Dr. Clowse warned.
Although teratogenicity has not been observed in animals on belimumab, GlaxoSmithKline recently launched a global Benlysta Pregnancy Registry to prospectively collect data on birth defects and other pregnancy outcomes from women receiving belimumab within the 4 months prior to and/or during pregnancy (telephone: 1-877-681-6296).
Dr. Clowse said she recently began putting most of her pregnant SLE patients on aspirin 81 mg/day to prevent preeclampsia. Data from high-risk, nonlupus patients suggest aspirin may decrease the risk of preterm birth, preeclampsia, maternal hypertension, and low-birth weight without increasing the risk of congenital anomalies or ductus arteriosus closure observed with regular aspirin.
"It also, to be honest, takes away that whole discussion of low anticardiolipin antibodies and what do you do," she added.
Pregnant women with SLE should be closely monitored by a rheumatologist and an obstetrician skilled in high-risk pregnancies. Key parameters to monitor are hypertension, particularly in the first trimester, as this can increase the risk of pregnancy loss, preterm birth, and preeclampsia by up to 40%; and proteinuria, which may rise modestly during pregnancy due to increased renal function. More than a doubling or a 1-g increase of proteinuria, however, should raise the alarm, Dr. Clowse said.
To achieve the best possible pregnancy outcome, women with SLE should be advised to avoid pregnancy when SLE is active. Dr. Clowse said it’s recently come to her attention that in North Carolina and other parts of the United States where abstinence-only education has been the law of the land for the past dozen years, this may mean having that first conversation about contraception with a patient already in her 20s.
"I think it’s really important that we address this with our rheumatology patients," she said.
Dr. Clowse said progesterone-only contraceptives are probably the safest method in SLE patients, with medroxyprogesterone injection (Depo-Provera) generally well tolerated, and the 3-year etonogestrel implant (Implanon) is better tolerated than the levonorgestrel implant (Norplant). She also advises her SLE patients to use barrier methods and to pick up levonorgestrel (Plan B One-Step) on the way home from the clinic to have on hand for emergencies.
Dr. Clowse reported consulting for UCB and receiving grant support from the Arthritis Foundation.
CHICAGO – The risk of active disease in pregnant women with systemic lupus erythematosus far outweighs the risks of most medications.
Indeed, the risk of pregnancy loss doubles if lupus is active during pregnancy and jumps fourfold if the autoimmune disease is active in the 3 months before conception.
"My general rule is that the inflammation of active lupus is more dangerous to a pregnancy than medications," said Dr. Megan Clowse, director of the Duke University Autoimmunity in Pregnancy Registry in Durham, N.C. "We don’t have a medication that will cause a 40% pregnancy loss. So I think it’s important to continue medications within this population, although some drugs are certainly better than others."
She advocates the use of hydroxychloroquine (Plaquenil) as the best way to prevent a systemic lupus erythematosus (SLE) flare. It’s a pregnancy category C drug because of reports of hearing abnormalities in children exposed to high doses of chloroquine (Aralen), but there are no clear fetal risks with hydroxychloroquine itself, particularly at the doses used by rheumatologists, she said. Moreover, several reports have suggested that hydroxychloroquine discontinuation during pregnancy may precipitate SLE flares, thereby worsening pregnancy prognosis.
The one exception to hydroxychloroquine use in SLE is the patient who’s been off the drug for years and is no longer symptomatic but becomes pregnant. "I don’t force those women back on their hydroxychloroquine, but basically everybody else should be on it," Dr. Clowse said at a symposium sponsored by the American College of Rheumatology.
For women with more active SLE, consider the use of azathioprine (Azasan, Imuran). It is a pregnancy category D drug due to the risk for fetal immunosuppression at delivery, but its use in SLE pregnancy is supported by extensive data among renal transplant patients, who have a higher rate of prematurity than SLE patients.
Azathioprine is most effective in preventing SLE flare in pregnancy, but Dr. Clowse said she has not been as impressed with its ability to treat flares during pregnancy. In her own recent study, azathioprine did not prevent pregnancy loss, and was actually associated with higher rates of loss among women with high-activity SLE.
When SLE flares occur, they need to be treated promptly, she stressed. Prednisone is probably the most effective treatment, although intravenous immunoglobulin may be a reasonable option. Prednisone is metabolized by the placenta, allowing only 10% of the maternal dose to reach the fetus. In contrast, the fluorinated corticosteroid betamethasone (Betnesol injection) is not metabolized and is transferred to the fetus, so it should not be used during pregnancy. Prednisone may decrease birth weight and is associated with a modest, threefold increased risk for cleft lip and palate, but this is really a first-trimester risk, she noted.
Drugs to avoid in pregnancy include cyclophosphamide (Cytoxan), mycophenolate mofetil (CellCept), and belimumab (Benlysta). A review of 26 pregnancies in 18 renal transplant patients receiving mycophenolate reported that 11 ended in spontaneous abortions and 10 in preterm births, and there were 4 cases of congenital anomalies (Transplantation 2006;82:1698-702). Not only was the 26% birth defect rate staggering compared with the 3% seen in the general population, but three of the infants had microtia. This was not simply underdeveloped pinnae, but the ears were located in the wrong place on the head, resulting in the babies being deaf, Dr. Clowse warned.
Although teratogenicity has not been observed in animals on belimumab, GlaxoSmithKline recently launched a global Benlysta Pregnancy Registry to prospectively collect data on birth defects and other pregnancy outcomes from women receiving belimumab within the 4 months prior to and/or during pregnancy (telephone: 1-877-681-6296).
Dr. Clowse said she recently began putting most of her pregnant SLE patients on aspirin 81 mg/day to prevent preeclampsia. Data from high-risk, nonlupus patients suggest aspirin may decrease the risk of preterm birth, preeclampsia, maternal hypertension, and low-birth weight without increasing the risk of congenital anomalies or ductus arteriosus closure observed with regular aspirin.
"It also, to be honest, takes away that whole discussion of low anticardiolipin antibodies and what do you do," she added.
Pregnant women with SLE should be closely monitored by a rheumatologist and an obstetrician skilled in high-risk pregnancies. Key parameters to monitor are hypertension, particularly in the first trimester, as this can increase the risk of pregnancy loss, preterm birth, and preeclampsia by up to 40%; and proteinuria, which may rise modestly during pregnancy due to increased renal function. More than a doubling or a 1-g increase of proteinuria, however, should raise the alarm, Dr. Clowse said.
To achieve the best possible pregnancy outcome, women with SLE should be advised to avoid pregnancy when SLE is active. Dr. Clowse said it’s recently come to her attention that in North Carolina and other parts of the United States where abstinence-only education has been the law of the land for the past dozen years, this may mean having that first conversation about contraception with a patient already in her 20s.
"I think it’s really important that we address this with our rheumatology patients," she said.
Dr. Clowse said progesterone-only contraceptives are probably the safest method in SLE patients, with medroxyprogesterone injection (Depo-Provera) generally well tolerated, and the 3-year etonogestrel implant (Implanon) is better tolerated than the levonorgestrel implant (Norplant). She also advises her SLE patients to use barrier methods and to pick up levonorgestrel (Plan B One-Step) on the way home from the clinic to have on hand for emergencies.
Dr. Clowse reported consulting for UCB and receiving grant support from the Arthritis Foundation.
EXPERT ANALYSIS FROM A SYMPOSIUM SPONSORED BY THE AMERICAN COLLEGE OF RHEUMATOLOGY
Lifestyle Messages After PCI Need to Be Hit Harder
MUNICH – Despite undergoing a lifesaving coronary intervention, patients are failing to heed the message from physicians to adopt a heart-healthy lifestyle, according to a patient survey.
Among 1,703 Swedish patients surveyed within 8 weeks of an acute percutaneous coronary intervention (PCI), 16% were still smoking, 45% had inadequate dietary habits, and just 47% were physically active, Dr. Joep Perk reported at the annual congress of the European Society of Cardiology.
"When we asked them, ‘Why did you get your myocardial infarction?’ they said, ‘It’s in the family, it’s my age. It has nothing to do with smoking or running around eating," Dr. Perk said.
"They thought it was something you could not influence and had to go to the doctor to get mended, and the next time it breaks down, you have to go back to the doctor again."
Patients, however, may not get that chance.
Patients who reported persistent smoking and nonadherence to diet and exercise had a 3.8-fold higher risk of myocardial infarction (MI), stroke, or death within 6 months of PCI in the massive OASIS-5 (Organization to Assess Strategies in Acute Ischemic Syndromes 5) study, involving 18,809 patients from 41 countries, observed Dr. Perk, a senior professor at Linnaeus University in Kalmar, Sweden, and editor of the European Journal of Preventive Cardiology.
In contrast, quitting smoking dramatically reduced the risk of MI (odds ratio, 0.57), as did diet and exercise adherence (OR, 0.52), he said.
Using the 6% post-PCI rate for all cardiac events reported in OASIS-5, Dr. Perk and his colleagues conducted the SPICI (Study of Patient Information after Coronary Intervention) study, and estimated that the expected cardiac event rate in the Swedish population would be 1,100-1,200 events annually.
Thus, a prudent estimate indicates that at least 400-500 cases of MI, cardiac death, or stroke could be prevented if the Swedish post-PCI population would adhere 100% to a cardioprotective lifestyle, saving the lives of 150-200 persons yearly, he reported in the poster presentation.
Clearly, cardiac rehabilitation programs need to find news ways to reach their patients. Many of the patients in SPICI reported searching the Internet or asking friends and relatives for advice post PCI, while only 78% were invited to exercise training programs and 71% received nutritional counseling.
"There is fantastic room for improvement," Dr. Perk said in a press briefing. "We feel cardiac rehabilitation has lost touch with modern interventional cardiology."
Part of the problem is that some physicians may not be aware of the "really explosive information" in OASIS-5, or may focus their message on cure rather than grim statistics and the need to modify bad habits. Others may reach out to their patients too soon after PCI, when they are in a state of "shock" and unable to process information about lifestyle changes, Dr. Perk said in an interview.
"Timing is very important," he said. "Patients need time to think and consider what they can do themselves."
In this study, most patients expressed the belief that after PCI their disease was cured. Or they thought that if it were to come back, it would merely mean another trip to the PCI lab, an attitude that Dr. Perk considers "a fatal mistake."
Patients seemed to comprehend the need for lifestyle changes equally as poorly whether the message was delivered by physicians or nurses. Patient age and gender also had no significant impact on the uptake of healthy lifestyle choices, he said.
If physicians want to get their message across, he suggests they engage the patient’s partner and family, use modern educational technology such as interactive Internet-based models or support groups, and engage educators to help hone the communication skills of health professionals.
Dr. Michel Bertrand, past president of the European Society of Cardiology (ESC), said in an interview, "I am pessimistic because in spite of all that we tell our patients – ‘You need to stop smoking, you need to exercise, you need to have a good diet’ – they don’t do it."
He pointed to data from the cross-sectional EUROASPIRE I, II, and III studies showing that blood pressure, lipid targets, and smoking rates remained the same among patients with coronary heart disease despite a substantial increase in antihypertensive and lipid-lowering drugs (Lancet 2009;373:929-40).
In addition, investigators with the FAST-MI (French Registry of Acute ST-Elevation or non-ST-elevation Myocardial Infarction) study reported at the same ESC meeting that the proportion of female ST-segment elevation MI patients under age 60 more than doubled, from 11.8% to 25.5%, and the number under age 50 tripled, from 3.7% to 11.1% from 1995 to 2010 (JAMA Aug. 27 [doi: 10.1001/2012.jama.11348]).
Over the same period, the proportion of younger women (under age 60) who were current smokers jumped from 37% to 73%, and the prevalence of obesity rose from 18% to 27%.
"The problem is young women; they are smoking more and more and more," said Dr. Bertrand. "In my own experience, I have been obliged in the past to find the possibility to have heart transplantation for a woman under 30. Under 30! And why? It’s because [of] the pill and tobacco. This is a bomb. Tobacco is a bomb."
Click here to view a video interview with Dr. Perk.
Dr. Perk and Dr. Bertrand reported having no relevant conflicts.
MUNICH – Despite undergoing a lifesaving coronary intervention, patients are failing to heed the message from physicians to adopt a heart-healthy lifestyle, according to a patient survey.
Among 1,703 Swedish patients surveyed within 8 weeks of an acute percutaneous coronary intervention (PCI), 16% were still smoking, 45% had inadequate dietary habits, and just 47% were physically active, Dr. Joep Perk reported at the annual congress of the European Society of Cardiology.
"When we asked them, ‘Why did you get your myocardial infarction?’ they said, ‘It’s in the family, it’s my age. It has nothing to do with smoking or running around eating," Dr. Perk said.
"They thought it was something you could not influence and had to go to the doctor to get mended, and the next time it breaks down, you have to go back to the doctor again."
Patients, however, may not get that chance.
Patients who reported persistent smoking and nonadherence to diet and exercise had a 3.8-fold higher risk of myocardial infarction (MI), stroke, or death within 6 months of PCI in the massive OASIS-5 (Organization to Assess Strategies in Acute Ischemic Syndromes 5) study, involving 18,809 patients from 41 countries, observed Dr. Perk, a senior professor at Linnaeus University in Kalmar, Sweden, and editor of the European Journal of Preventive Cardiology.
In contrast, quitting smoking dramatically reduced the risk of MI (odds ratio, 0.57), as did diet and exercise adherence (OR, 0.52), he said.
Using the 6% post-PCI rate for all cardiac events reported in OASIS-5, Dr. Perk and his colleagues conducted the SPICI (Study of Patient Information after Coronary Intervention) study, and estimated that the expected cardiac event rate in the Swedish population would be 1,100-1,200 events annually.
Thus, a prudent estimate indicates that at least 400-500 cases of MI, cardiac death, or stroke could be prevented if the Swedish post-PCI population would adhere 100% to a cardioprotective lifestyle, saving the lives of 150-200 persons yearly, he reported in the poster presentation.
Clearly, cardiac rehabilitation programs need to find news ways to reach their patients. Many of the patients in SPICI reported searching the Internet or asking friends and relatives for advice post PCI, while only 78% were invited to exercise training programs and 71% received nutritional counseling.
"There is fantastic room for improvement," Dr. Perk said in a press briefing. "We feel cardiac rehabilitation has lost touch with modern interventional cardiology."
Part of the problem is that some physicians may not be aware of the "really explosive information" in OASIS-5, or may focus their message on cure rather than grim statistics and the need to modify bad habits. Others may reach out to their patients too soon after PCI, when they are in a state of "shock" and unable to process information about lifestyle changes, Dr. Perk said in an interview.
"Timing is very important," he said. "Patients need time to think and consider what they can do themselves."
In this study, most patients expressed the belief that after PCI their disease was cured. Or they thought that if it were to come back, it would merely mean another trip to the PCI lab, an attitude that Dr. Perk considers "a fatal mistake."
Patients seemed to comprehend the need for lifestyle changes equally as poorly whether the message was delivered by physicians or nurses. Patient age and gender also had no significant impact on the uptake of healthy lifestyle choices, he said.
If physicians want to get their message across, he suggests they engage the patient’s partner and family, use modern educational technology such as interactive Internet-based models or support groups, and engage educators to help hone the communication skills of health professionals.
Dr. Michel Bertrand, past president of the European Society of Cardiology (ESC), said in an interview, "I am pessimistic because in spite of all that we tell our patients – ‘You need to stop smoking, you need to exercise, you need to have a good diet’ – they don’t do it."
He pointed to data from the cross-sectional EUROASPIRE I, II, and III studies showing that blood pressure, lipid targets, and smoking rates remained the same among patients with coronary heart disease despite a substantial increase in antihypertensive and lipid-lowering drugs (Lancet 2009;373:929-40).
In addition, investigators with the FAST-MI (French Registry of Acute ST-Elevation or non-ST-elevation Myocardial Infarction) study reported at the same ESC meeting that the proportion of female ST-segment elevation MI patients under age 60 more than doubled, from 11.8% to 25.5%, and the number under age 50 tripled, from 3.7% to 11.1% from 1995 to 2010 (JAMA Aug. 27 [doi: 10.1001/2012.jama.11348]).
Over the same period, the proportion of younger women (under age 60) who were current smokers jumped from 37% to 73%, and the prevalence of obesity rose from 18% to 27%.
"The problem is young women; they are smoking more and more and more," said Dr. Bertrand. "In my own experience, I have been obliged in the past to find the possibility to have heart transplantation for a woman under 30. Under 30! And why? It’s because [of] the pill and tobacco. This is a bomb. Tobacco is a bomb."
Click here to view a video interview with Dr. Perk.
Dr. Perk and Dr. Bertrand reported having no relevant conflicts.
MUNICH – Despite undergoing a lifesaving coronary intervention, patients are failing to heed the message from physicians to adopt a heart-healthy lifestyle, according to a patient survey.
Among 1,703 Swedish patients surveyed within 8 weeks of an acute percutaneous coronary intervention (PCI), 16% were still smoking, 45% had inadequate dietary habits, and just 47% were physically active, Dr. Joep Perk reported at the annual congress of the European Society of Cardiology.
"When we asked them, ‘Why did you get your myocardial infarction?’ they said, ‘It’s in the family, it’s my age. It has nothing to do with smoking or running around eating," Dr. Perk said.
"They thought it was something you could not influence and had to go to the doctor to get mended, and the next time it breaks down, you have to go back to the doctor again."
Patients, however, may not get that chance.
Patients who reported persistent smoking and nonadherence to diet and exercise had a 3.8-fold higher risk of myocardial infarction (MI), stroke, or death within 6 months of PCI in the massive OASIS-5 (Organization to Assess Strategies in Acute Ischemic Syndromes 5) study, involving 18,809 patients from 41 countries, observed Dr. Perk, a senior professor at Linnaeus University in Kalmar, Sweden, and editor of the European Journal of Preventive Cardiology.
In contrast, quitting smoking dramatically reduced the risk of MI (odds ratio, 0.57), as did diet and exercise adherence (OR, 0.52), he said.
Using the 6% post-PCI rate for all cardiac events reported in OASIS-5, Dr. Perk and his colleagues conducted the SPICI (Study of Patient Information after Coronary Intervention) study, and estimated that the expected cardiac event rate in the Swedish population would be 1,100-1,200 events annually.
Thus, a prudent estimate indicates that at least 400-500 cases of MI, cardiac death, or stroke could be prevented if the Swedish post-PCI population would adhere 100% to a cardioprotective lifestyle, saving the lives of 150-200 persons yearly, he reported in the poster presentation.
Clearly, cardiac rehabilitation programs need to find news ways to reach their patients. Many of the patients in SPICI reported searching the Internet or asking friends and relatives for advice post PCI, while only 78% were invited to exercise training programs and 71% received nutritional counseling.
"There is fantastic room for improvement," Dr. Perk said in a press briefing. "We feel cardiac rehabilitation has lost touch with modern interventional cardiology."
Part of the problem is that some physicians may not be aware of the "really explosive information" in OASIS-5, or may focus their message on cure rather than grim statistics and the need to modify bad habits. Others may reach out to their patients too soon after PCI, when they are in a state of "shock" and unable to process information about lifestyle changes, Dr. Perk said in an interview.
"Timing is very important," he said. "Patients need time to think and consider what they can do themselves."
In this study, most patients expressed the belief that after PCI their disease was cured. Or they thought that if it were to come back, it would merely mean another trip to the PCI lab, an attitude that Dr. Perk considers "a fatal mistake."
Patients seemed to comprehend the need for lifestyle changes equally as poorly whether the message was delivered by physicians or nurses. Patient age and gender also had no significant impact on the uptake of healthy lifestyle choices, he said.
If physicians want to get their message across, he suggests they engage the patient’s partner and family, use modern educational technology such as interactive Internet-based models or support groups, and engage educators to help hone the communication skills of health professionals.
Dr. Michel Bertrand, past president of the European Society of Cardiology (ESC), said in an interview, "I am pessimistic because in spite of all that we tell our patients – ‘You need to stop smoking, you need to exercise, you need to have a good diet’ – they don’t do it."
He pointed to data from the cross-sectional EUROASPIRE I, II, and III studies showing that blood pressure, lipid targets, and smoking rates remained the same among patients with coronary heart disease despite a substantial increase in antihypertensive and lipid-lowering drugs (Lancet 2009;373:929-40).
In addition, investigators with the FAST-MI (French Registry of Acute ST-Elevation or non-ST-elevation Myocardial Infarction) study reported at the same ESC meeting that the proportion of female ST-segment elevation MI patients under age 60 more than doubled, from 11.8% to 25.5%, and the number under age 50 tripled, from 3.7% to 11.1% from 1995 to 2010 (JAMA Aug. 27 [doi: 10.1001/2012.jama.11348]).
Over the same period, the proportion of younger women (under age 60) who were current smokers jumped from 37% to 73%, and the prevalence of obesity rose from 18% to 27%.
"The problem is young women; they are smoking more and more and more," said Dr. Bertrand. "In my own experience, I have been obliged in the past to find the possibility to have heart transplantation for a woman under 30. Under 30! And why? It’s because [of] the pill and tobacco. This is a bomb. Tobacco is a bomb."
Click here to view a video interview with Dr. Perk.
Dr. Perk and Dr. Bertrand reported having no relevant conflicts.
AT THE ANNUAL CONGRESS OF THE EUROPEAN SOCIETY OF CARDIOLOGY
Major Finding: Among 1,703 Swedish patients surveyed within 8 weeks of an acute percutaneous coronary intervention (PCI), 16% were still smoking, 45% had inadequate dietary habits, and only 47% were physically active.
Data Source: Retrospective analysis of 1,800 patients who underwent acute percutaneous coronary intervention.
Disclosures: Dr. Perk and Dr. Bertrand report no relevant conflicts of interest.
No Benefit of Balloon Pump in Acute MI With Shock
MUNICH – Although it is routinely used in clinical practice, the intra-aortic balloon pump provided no early mortality benefit in patients with myocardial infarction complicated by cardiogenic shock in the randomized IABP-SHOCK II study.
The primary end point of 30-day all-cause mortality was 41.3% in controls and 39.7% in patients receiving intra-aortic balloon pump (IABP) support, a difference that was not significant. None of the subgroups that were analyzed derived benefit.
Use of an IABP also failed to improve any of the secondary outcomes of the trial, the largest to date in patients with cardiogenic shock, Dr. Holger Thiele reported at the annual congress of the European Society of Cardiology (ESC).
However, "it’s too early to say that it’s the end of the pump," Dr. Thiele said in an interview. "Before we close this chapter, I think we have to wait for long-term follow-up data."
While awaiting 6- and 12-month mortality data, which could be reported by the end of 2013, use of IABPs is likely to go down because of the negative results of IABP-SHOCK II (Intraaortic Balloon Pump in Cardiogenic Shock II), he said.
Discussant Dr. Uta Hoppe, of the Paracelsus Medical University of Salzburg, Austria, agreed that it’s unlikely clinicians can improve the outcome of patients by implanting more IABPs.
"These data rather show that IABPs are not useful for most of these patients, and we still have to define the individuals that might derive benefit," she said. "Particularly, if the long-term data would support and confirm this neutral effect of IABP, I think that our guidelines have to be reconsidered."
Before the trial, IABP results were available from registries and only one randomized controlled trial of just 57 patients. Results were mixed, possibly explaining why the IABP is currently used in only about 35% of cardiogenic shock patients in Europe and 39% in the United States, said Dr. Thiele, professor of medicine at the University of Leipzig (Germany) Heart Center.
Despite the limited data, IABPs became part of contemporary practice and were carried forward through various iterations of the ESC guidelines and American College of Cardiology/American Heart Association guidelines with a class I recommendation.
The lack of solid data, however, was likely behind the decision to downgrade the IABP recommendation to IIb in the new ESC guidelines for ST-segment elevation acute MI, presented just 24 hours earlier at the meeting, Dr. Thiele said. It was also the impetus for IABP-SHOCK II.
In the trial, investigators at 37 German sites randomized 600 acute MI patients in cardiogenic shock to either percutaneous coronary intervention plus IABP insertion and optimal medical therapy or PCI plus medical therapy only.
Nearly 50% of patients underwent resuscitation before randomization, 80% had mild vessel disease that was the cause of the shock, and 96% underwent primary PCI. Notably, the timing of pump insertion was left up to the investigators, with 87% of IABPs inserted after the procedure.
There were no significant differences between groups in the secondary outcomes of renal function, serum lactate, and inflammatory reaction, Dr. Thiele said. There was a significant benefit on the Simplified Acute Physiology Score-II intensive care instrument, favoring the balloon pump on day 2 and day 3 post procedure, but this was attenuated and no longer significant on day 4.
Dr. Thiele said in an interview that he will likely stop using IABPs in cardiogenic shock patients because the trial has shown that 60% of patients will not need anything else, if treated according to guidelines with early revascularization and optimal management.
He went on to say that, although some may be tempted to turn to left ventricular assist devices in high-risk patients, data are almost nonexistent comparing assist devices with the balloon pump. Only 5.5% of patients received LVADs in IABP-SHOCK II, and mortality was high at 67%. "Nevertheless, if you have a young patient who is not responding to the standard therapy, then I would always put in such a percutaneous left ventricular assist device," he added.
The study was simultaneously published in the New England Journal of Medicine (2012 Aug. 27 [doi: 10.1056/NEJMoa1208410]).
In an accompanying editorial (2012 Aug. 27 [doi: 10.1056/NEJMe1209601]), Dr. Christopher M. O’Connor and Dr. Joseph G. Rogers, both of Duke University in Durham, N.C., called the results surprising, and said that "on the basis of the findings of the IABP-SHOCK II trial, we must move forward with the understanding that a cardiovascular condition with 40% mortality at 30 days remains unacceptable."
Dr. Thiele reported research funding from several pharmaceutical and device firms. Dr. Hoppe did not provide disclosures. The trial was funded by the German Research Foundation, the German Heart Research Foundation, and other organizations, as well as by Maquet Cardiopulmonary and Teleflex Medical.
MUNICH – Although it is routinely used in clinical practice, the intra-aortic balloon pump provided no early mortality benefit in patients with myocardial infarction complicated by cardiogenic shock in the randomized IABP-SHOCK II study.
The primary end point of 30-day all-cause mortality was 41.3% in controls and 39.7% in patients receiving intra-aortic balloon pump (IABP) support, a difference that was not significant. None of the subgroups that were analyzed derived benefit.
Use of an IABP also failed to improve any of the secondary outcomes of the trial, the largest to date in patients with cardiogenic shock, Dr. Holger Thiele reported at the annual congress of the European Society of Cardiology (ESC).
However, "it’s too early to say that it’s the end of the pump," Dr. Thiele said in an interview. "Before we close this chapter, I think we have to wait for long-term follow-up data."
While awaiting 6- and 12-month mortality data, which could be reported by the end of 2013, use of IABPs is likely to go down because of the negative results of IABP-SHOCK II (Intraaortic Balloon Pump in Cardiogenic Shock II), he said.
Discussant Dr. Uta Hoppe, of the Paracelsus Medical University of Salzburg, Austria, agreed that it’s unlikely clinicians can improve the outcome of patients by implanting more IABPs.
"These data rather show that IABPs are not useful for most of these patients, and we still have to define the individuals that might derive benefit," she said. "Particularly, if the long-term data would support and confirm this neutral effect of IABP, I think that our guidelines have to be reconsidered."
Before the trial, IABP results were available from registries and only one randomized controlled trial of just 57 patients. Results were mixed, possibly explaining why the IABP is currently used in only about 35% of cardiogenic shock patients in Europe and 39% in the United States, said Dr. Thiele, professor of medicine at the University of Leipzig (Germany) Heart Center.
Despite the limited data, IABPs became part of contemporary practice and were carried forward through various iterations of the ESC guidelines and American College of Cardiology/American Heart Association guidelines with a class I recommendation.
The lack of solid data, however, was likely behind the decision to downgrade the IABP recommendation to IIb in the new ESC guidelines for ST-segment elevation acute MI, presented just 24 hours earlier at the meeting, Dr. Thiele said. It was also the impetus for IABP-SHOCK II.
In the trial, investigators at 37 German sites randomized 600 acute MI patients in cardiogenic shock to either percutaneous coronary intervention plus IABP insertion and optimal medical therapy or PCI plus medical therapy only.
Nearly 50% of patients underwent resuscitation before randomization, 80% had mild vessel disease that was the cause of the shock, and 96% underwent primary PCI. Notably, the timing of pump insertion was left up to the investigators, with 87% of IABPs inserted after the procedure.
There were no significant differences between groups in the secondary outcomes of renal function, serum lactate, and inflammatory reaction, Dr. Thiele said. There was a significant benefit on the Simplified Acute Physiology Score-II intensive care instrument, favoring the balloon pump on day 2 and day 3 post procedure, but this was attenuated and no longer significant on day 4.
Dr. Thiele said in an interview that he will likely stop using IABPs in cardiogenic shock patients because the trial has shown that 60% of patients will not need anything else, if treated according to guidelines with early revascularization and optimal management.
He went on to say that, although some may be tempted to turn to left ventricular assist devices in high-risk patients, data are almost nonexistent comparing assist devices with the balloon pump. Only 5.5% of patients received LVADs in IABP-SHOCK II, and mortality was high at 67%. "Nevertheless, if you have a young patient who is not responding to the standard therapy, then I would always put in such a percutaneous left ventricular assist device," he added.
The study was simultaneously published in the New England Journal of Medicine (2012 Aug. 27 [doi: 10.1056/NEJMoa1208410]).
In an accompanying editorial (2012 Aug. 27 [doi: 10.1056/NEJMe1209601]), Dr. Christopher M. O’Connor and Dr. Joseph G. Rogers, both of Duke University in Durham, N.C., called the results surprising, and said that "on the basis of the findings of the IABP-SHOCK II trial, we must move forward with the understanding that a cardiovascular condition with 40% mortality at 30 days remains unacceptable."
Dr. Thiele reported research funding from several pharmaceutical and device firms. Dr. Hoppe did not provide disclosures. The trial was funded by the German Research Foundation, the German Heart Research Foundation, and other organizations, as well as by Maquet Cardiopulmonary and Teleflex Medical.
MUNICH – Although it is routinely used in clinical practice, the intra-aortic balloon pump provided no early mortality benefit in patients with myocardial infarction complicated by cardiogenic shock in the randomized IABP-SHOCK II study.
The primary end point of 30-day all-cause mortality was 41.3% in controls and 39.7% in patients receiving intra-aortic balloon pump (IABP) support, a difference that was not significant. None of the subgroups that were analyzed derived benefit.
Use of an IABP also failed to improve any of the secondary outcomes of the trial, the largest to date in patients with cardiogenic shock, Dr. Holger Thiele reported at the annual congress of the European Society of Cardiology (ESC).
However, "it’s too early to say that it’s the end of the pump," Dr. Thiele said in an interview. "Before we close this chapter, I think we have to wait for long-term follow-up data."
While awaiting 6- and 12-month mortality data, which could be reported by the end of 2013, use of IABPs is likely to go down because of the negative results of IABP-SHOCK II (Intraaortic Balloon Pump in Cardiogenic Shock II), he said.
Discussant Dr. Uta Hoppe, of the Paracelsus Medical University of Salzburg, Austria, agreed that it’s unlikely clinicians can improve the outcome of patients by implanting more IABPs.
"These data rather show that IABPs are not useful for most of these patients, and we still have to define the individuals that might derive benefit," she said. "Particularly, if the long-term data would support and confirm this neutral effect of IABP, I think that our guidelines have to be reconsidered."
Before the trial, IABP results were available from registries and only one randomized controlled trial of just 57 patients. Results were mixed, possibly explaining why the IABP is currently used in only about 35% of cardiogenic shock patients in Europe and 39% in the United States, said Dr. Thiele, professor of medicine at the University of Leipzig (Germany) Heart Center.
Despite the limited data, IABPs became part of contemporary practice and were carried forward through various iterations of the ESC guidelines and American College of Cardiology/American Heart Association guidelines with a class I recommendation.
The lack of solid data, however, was likely behind the decision to downgrade the IABP recommendation to IIb in the new ESC guidelines for ST-segment elevation acute MI, presented just 24 hours earlier at the meeting, Dr. Thiele said. It was also the impetus for IABP-SHOCK II.
In the trial, investigators at 37 German sites randomized 600 acute MI patients in cardiogenic shock to either percutaneous coronary intervention plus IABP insertion and optimal medical therapy or PCI plus medical therapy only.
Nearly 50% of patients underwent resuscitation before randomization, 80% had mild vessel disease that was the cause of the shock, and 96% underwent primary PCI. Notably, the timing of pump insertion was left up to the investigators, with 87% of IABPs inserted after the procedure.
There were no significant differences between groups in the secondary outcomes of renal function, serum lactate, and inflammatory reaction, Dr. Thiele said. There was a significant benefit on the Simplified Acute Physiology Score-II intensive care instrument, favoring the balloon pump on day 2 and day 3 post procedure, but this was attenuated and no longer significant on day 4.
Dr. Thiele said in an interview that he will likely stop using IABPs in cardiogenic shock patients because the trial has shown that 60% of patients will not need anything else, if treated according to guidelines with early revascularization and optimal management.
He went on to say that, although some may be tempted to turn to left ventricular assist devices in high-risk patients, data are almost nonexistent comparing assist devices with the balloon pump. Only 5.5% of patients received LVADs in IABP-SHOCK II, and mortality was high at 67%. "Nevertheless, if you have a young patient who is not responding to the standard therapy, then I would always put in such a percutaneous left ventricular assist device," he added.
The study was simultaneously published in the New England Journal of Medicine (2012 Aug. 27 [doi: 10.1056/NEJMoa1208410]).
In an accompanying editorial (2012 Aug. 27 [doi: 10.1056/NEJMe1209601]), Dr. Christopher M. O’Connor and Dr. Joseph G. Rogers, both of Duke University in Durham, N.C., called the results surprising, and said that "on the basis of the findings of the IABP-SHOCK II trial, we must move forward with the understanding that a cardiovascular condition with 40% mortality at 30 days remains unacceptable."
Dr. Thiele reported research funding from several pharmaceutical and device firms. Dr. Hoppe did not provide disclosures. The trial was funded by the German Research Foundation, the German Heart Research Foundation, and other organizations, as well as by Maquet Cardiopulmonary and Teleflex Medical.
AT THE ANNUAL CONGRESS OF THE EUROPEAN SOCIETY OF CARDIOLOGY
Major Finding: The primary end point of 30-day all-cause mortality was 41.3% in controls and 39.7% in patients receiving IABP support, a nonsignificant difference.
Data Source: IABP-SHOCK II was a phase IV trial that randomized 600 acute MI patients in cardiogenic shock to either PCI plus IABP insertion and optimal medical therapy or PCI plus medical therapy only.
Disclosures: Dr. Thiele reported research funding from several pharmaceutical and device firms. Dr. Hoppe did not provide disclosures. The trial was funded by the German Research Foundation, the German Heart Research Foundation, and other organizations, as well as by Maquet Cardiopulmonary and Teleflex Medical.
