ACC Conference Coverage

ORLANDO – Patients who received vouchers to cover copayments were more likely to receive prescriptions for more effective antiplatelet medication, according to data from a multicenter, randomized trial.

“We know that guidelines are very clear; we need to treat patients with antiplatelet therapy for 12 months,” and that the most potent drug, ticagrelor, should be used, Tracy Wang, MD, of Duke University, Durham, N.C., said in a video interview at the annual meeting of the American College of Cardiology. However, in the United States, clopidogrel, though less effective, is prescribed much more often, and many patients discontinue their P2Y₁₂ inhibitor therapy within the first year because of cost, she added.

“We hypothesized that, by reducing the out of pocket costs, treatment would be more evidence driven, rather than driven by what patients could afford,” she said.

The Affordability and Real-World Antiplatelet Treatment Effectiveness After Myocardial Infarction Study (ARTEMIS) included 11,001 MI patients at 301 hospitals across the United States. Patients in the treatment hospital group received a voucher to use at a pharmacy or through a mail-order pharmacy to reduce out of pocket costs. Randomization occurred at the hospital level, and hospital characteristics were similar between the groups.

Overall, patients in the treatment group were significantly more likely to receive a prescription for ticagrelor than clopidogrel (60% vs. 36%); 55% and 32% of patients in the usual care group were prescribed ticagrelor and clopidogrel, respectively. Nonpersistence, defined as a gap in P2Y₁₂-inhibitor use of at least 30 days within 1 year, was significantly lower in the treatment group than it was in the usual care group based on patient reported analysis (13% vs. 16%).

However, the incidence of major adverse cardiac events was roughly 10% in both groups. The similar outcomes may stem from the fact that 28% of patients with vouchers did not fill their prescriptions for reasons that the study did not explore, said Dr. Wang.

All patients had health insurance: 64% private, 42% Medicare, 9% Medicaid. The average age of the patients was 62 years, and 31% were women. Patient demographics and clinical characteristics were similar between the groups.

The vouchers affected choice of treatment but didn’t help clinical outcomes, which suggests that copayment reduction should be part of a broader strategy to help patients with adherence over time, said Dr. Wang.

Next steps for research include taking a subset of patients who are more likely to be nonadherent and at high risk for adverse events and targeting them for additional intervention, she noted.

Discussant Craig J. Beavers, PharmD, of the University of Kentucky College of Pharmacy, Lexington, agreed that a multipronged approach is needed to get patients to take their medicines. “We have to figure out what other barriers there are,” he said. “The real trick is, even if you lead a horse to water, how to get them to drink it,” he said.

The study was funded by AstraZeneca. Dr. Wang disclosed relationships with companies including Gilead Sciences, Merck, and Sanofi Pasteur. Dr. Beavers had no financial conflicts to disclose.

SOURCE: Wang T. ACC 18.

ORLANDO – Patients who received vouchers to cover copayments were more likely to receive prescriptions for more effective antiplatelet medication, according to data from a multicenter, randomized trial.

“We know that guidelines are very clear; we need to treat patients with antiplatelet therapy for 12 months,” and that the most potent drug, ticagrelor, should be used, Tracy Wang, MD, of Duke University, Durham, N.C., said in a video interview at the annual meeting of the American College of Cardiology. However, in the United States, clopidogrel, though less effective, is prescribed much more often, and many patients discontinue their P2Y₁₂ inhibitor therapy within the first year because of cost, she added.

“We hypothesized that, by reducing the out of pocket costs, treatment would be more evidence driven, rather than driven by what patients could afford,” she said.

The Affordability and Real-World Antiplatelet Treatment Effectiveness After Myocardial Infarction Study (ARTEMIS) included 11,001 MI patients at 301 hospitals across the United States. Patients in the treatment hospital group received a voucher to use at a pharmacy or through a mail-order pharmacy to reduce out of pocket costs. Randomization occurred at the hospital level, and hospital characteristics were similar between the groups.

Overall, patients in the treatment group were significantly more likely to receive a prescription for ticagrelor than clopidogrel (60% vs. 36%); 55% and 32% of patients in the usual care group were prescribed ticagrelor and clopidogrel, respectively. Nonpersistence, defined as a gap in P2Y₁₂-inhibitor use of at least 30 days within 1 year, was significantly lower in the treatment group than it was in the usual care group based on patient reported analysis (13% vs. 16%).

However, the incidence of major adverse cardiac events was roughly 10% in both groups. The similar outcomes may stem from the fact that 28% of patients with vouchers did not fill their prescriptions for reasons that the study did not explore, said Dr. Wang.

All patients had health insurance: 64% private, 42% Medicare, 9% Medicaid. The average age of the patients was 62 years, and 31% were women. Patient demographics and clinical characteristics were similar between the groups.

The vouchers affected choice of treatment but didn’t help clinical outcomes, which suggests that copayment reduction should be part of a broader strategy to help patients with adherence over time, said Dr. Wang.

Next steps for research include taking a subset of patients who are more likely to be nonadherent and at high risk for adverse events and targeting them for additional intervention, she noted.

Discussant Craig J. Beavers, PharmD, of the University of Kentucky College of Pharmacy, Lexington, agreed that a multipronged approach is needed to get patients to take their medicines. “We have to figure out what other barriers there are,” he said. “The real trick is, even if you lead a horse to water, how to get them to drink it,” he said.

The study was funded by AstraZeneca. Dr. Wang disclosed relationships with companies including Gilead Sciences, Merck, and Sanofi Pasteur. Dr. Beavers had no financial conflicts to disclose.

SOURCE: Wang T. ACC 18.

ORLANDO – Patients who received vouchers to cover copayments were more likely to receive prescriptions for more effective antiplatelet medication, according to data from a multicenter, randomized trial.

“We know that guidelines are very clear; we need to treat patients with antiplatelet therapy for 12 months,” and that the most potent drug, ticagrelor, should be used, Tracy Wang, MD, of Duke University, Durham, N.C., said in a video interview at the annual meeting of the American College of Cardiology. However, in the United States, clopidogrel, though less effective, is prescribed much more often, and many patients discontinue their P2Y₁₂ inhibitor therapy within the first year because of cost, she added.

“We hypothesized that, by reducing the out of pocket costs, treatment would be more evidence driven, rather than driven by what patients could afford,” she said.

The Affordability and Real-World Antiplatelet Treatment Effectiveness After Myocardial Infarction Study (ARTEMIS) included 11,001 MI patients at 301 hospitals across the United States. Patients in the treatment hospital group received a voucher to use at a pharmacy or through a mail-order pharmacy to reduce out of pocket costs. Randomization occurred at the hospital level, and hospital characteristics were similar between the groups.

Overall, patients in the treatment group were significantly more likely to receive a prescription for ticagrelor than clopidogrel (60% vs. 36%); 55% and 32% of patients in the usual care group were prescribed ticagrelor and clopidogrel, respectively. Nonpersistence, defined as a gap in P2Y₁₂-inhibitor use of at least 30 days within 1 year, was significantly lower in the treatment group than it was in the usual care group based on patient reported analysis (13% vs. 16%).

However, the incidence of major adverse cardiac events was roughly 10% in both groups. The similar outcomes may stem from the fact that 28% of patients with vouchers did not fill their prescriptions for reasons that the study did not explore, said Dr. Wang.

All patients had health insurance: 64% private, 42% Medicare, 9% Medicaid. The average age of the patients was 62 years, and 31% were women. Patient demographics and clinical characteristics were similar between the groups.

The vouchers affected choice of treatment but didn’t help clinical outcomes, which suggests that copayment reduction should be part of a broader strategy to help patients with adherence over time, said Dr. Wang.

Next steps for research include taking a subset of patients who are more likely to be nonadherent and at high risk for adverse events and targeting them for additional intervention, she noted.

Discussant Craig J. Beavers, PharmD, of the University of Kentucky College of Pharmacy, Lexington, agreed that a multipronged approach is needed to get patients to take their medicines. “We have to figure out what other barriers there are,” he said. “The real trick is, even if you lead a horse to water, how to get them to drink it,” he said.

The study was funded by AstraZeneca. Dr. Wang disclosed relationships with companies including Gilead Sciences, Merck, and Sanofi Pasteur. Dr. Beavers had no financial conflicts to disclose.

SOURCE: Wang T. ACC 18.

ORLANDO – Black men who received a pharmacist-led intervention in their local barbershops showed significantly improved blood pressure after 6 months, compared with controls, in a randomized trial of 319 individuals.

“Non-Hispanic black men still have the highest hypertension death rate of any group in the country. Something like 60% of black men have blood pressure of 140/90 or higher,” but they have relatively low rates of physician interaction for blood pressure management, compared with other groups, Ronald G. Victor, MD, of Cedars-Sinai Medical Center, Los Angeles, said in a video interview at the annual meeting of the American College of Cardiology.

“Health outreach to barbershops has been well established in the lay press, but they only scratch the surface in terms of a scientific evaluation, and that’s what we did,” he noted.

The primary outcome was a change in systolic blood pressure at 6 months. The average decrease was 27.0 mm Hg in the intervention group, compared with 9.3 mm Hg in the control group.

cardnews@frontlinemedcom.com

SOURCE: Victor R et al. ACC 2018.

ORLANDO – Black men who received a pharmacist-led intervention in their local barbershops showed significantly improved blood pressure after 6 months, compared with controls, in a randomized trial of 319 individuals.

“Non-Hispanic black men still have the highest hypertension death rate of any group in the country. Something like 60% of black men have blood pressure of 140/90 or higher,” but they have relatively low rates of physician interaction for blood pressure management, compared with other groups, Ronald G. Victor, MD, of Cedars-Sinai Medical Center, Los Angeles, said in a video interview at the annual meeting of the American College of Cardiology.

“Health outreach to barbershops has been well established in the lay press, but they only scratch the surface in terms of a scientific evaluation, and that’s what we did,” he noted.

The primary outcome was a change in systolic blood pressure at 6 months. The average decrease was 27.0 mm Hg in the intervention group, compared with 9.3 mm Hg in the control group.

cardnews@frontlinemedcom.com

SOURCE: Victor R et al. ACC 2018.

ORLANDO – Black men who received a pharmacist-led intervention in their local barbershops showed significantly improved blood pressure after 6 months, compared with controls, in a randomized trial of 319 individuals.

“Non-Hispanic black men still have the highest hypertension death rate of any group in the country. Something like 60% of black men have blood pressure of 140/90 or higher,” but they have relatively low rates of physician interaction for blood pressure management, compared with other groups, Ronald G. Victor, MD, of Cedars-Sinai Medical Center, Los Angeles, said in a video interview at the annual meeting of the American College of Cardiology.

“Health outreach to barbershops has been well established in the lay press, but they only scratch the surface in terms of a scientific evaluation, and that’s what we did,” he noted.

The primary outcome was a change in systolic blood pressure at 6 months. The average decrease was 27.0 mm Hg in the intervention group, compared with 9.3 mm Hg in the control group.

cardnews@frontlinemedcom.com

SOURCE: Victor R et al. ACC 2018.

ORLANDO – Treating patients who developed myocardial injury after noncardiac surgery with the anticoagulant dabigatran significantly cut the rate of subsequent major vascular complications in a randomized, multicenter trial with 1,754 patients, a result that gives surgeons and physicians the first evidence-based intervention for treating a common postsurgical condition.

“Because we have not systematically followed noncardiac surgery patients, it’s easy to presume that everyone is okay, but all the epidemiology data show that these patients [who develop myocardial injury after noncardiac surgery] don’t do okay. We need to be aggressive with secondary prophylaxis,” P.J. Devereaux, MD, said at the annual meeting of the American College of Cardiology. “The unfortunate thing is that right now, we don’t do much for these patients,” said Dr. Devereaux, professor of medicine and director of cardiology at McMaster University in Hamilton, Ont.

Results from prior epidemiology studies have shown that, among the roughly 200 million patients who undergo noncardiac surgery worldwide each year, 8% will develop MINS (myocardial injury after noncardiac surgery) (Anesthesiology. 2014 March;120[3]:564-78). The myocardial injury that defines MINS is identified by either an overt MI that meets the universal definition, or an otherwise unexplained rise in serum troponin levels from baseline in the first couple of days after surgery. In the new study, Dr. Devereaux and his associates identified 80% of MINS by a troponin rise and 20% by a diagnosed MI.

The challenge in diagnosing MINS and then administering dabigatran will be implementation of this strategy into routine practice, commented Erin A. Bohula May, MD, a cardiologist at Brigham and Women’s Hospital in Boston. “The problem is, troponin is not routinely measured in postoperative patients. It will be hard to change practice,” she noted.

Dr. Devereaux agreed that a significant barrier is convincing clinicians, especially surgeons, to routinely measure a patient’s troponin levels just before and immediately after surgery. “People are lulled into a false sense of security because patients [who develop MINS] usually don’t have chest pain,” he said in a video interview. “When we first showed that patients with MINS have bad outcomes, that convinced some [surgeons] to measure troponin after surgery. “Showing we can do something about it” is another important step toward fostering more awareness of and interest in diagnosing and treating MINS.

The Management of Myocardial Injury After Noncardiac Surgery Trial (MANAGE) enrolled 1,754 patients at 82 centers in 19 countries. Researchers randomized patients to treatment with either 110 mg dabigatran b.i.d. or placebo. A majority of patients in both arms also received aspirin and a statin, treatments that Dr. Devereaux should be used along with dabigatran in routine practice, based on observational findings, although the efficacy of these drugs for MINS patients has not been tested in randomized studies. The study’s primary endpoint was the incidence of major vascular complications, a composite that included vascular mortality, nonfatal MI, nonfatal and nonhemorrhagic stroke, peripheral arterial thrombosis, amputation, or symptomatic venous thromboembolism.

After an average follow-up of 16 months, the primary endpoint occurred in 11% of the dabigatran-treated patients and in 15% of controls, which represented a 28% risk reduction that was statistically significant. The study’s primary safety endpoint was a composite of life-threatening, major, and critical organ bleeds, which occurred in 3% of the dabigatran-treated patients and in 4% of controls, a nonsignificant difference. The dabigatran-treated patients showed a significant excess of both minor bleeds – 15% compared with 10% in controls – and “nonsignificant” lower gastrointestinal bleeds, 4% with dabigatran and 1% in the controls. The dabigatran-treated patients also had a significantly higher incidence of dyspepsia.

MANAGE was funded by the Population Health Research Institute and had no commercial funding. Dr. Devereaux has received research support from Abbott Diagnostics, Boehringer Ingelheim, Philips Healthcare, and Roche Diagnostics. Dr. May has been a consultant to Daiichi Sankyo, Merck, and Servier and has received research funding from Eisai.

mzoler@frontlinemedcom.com

SOURCE: Devereaux P et al. ACC 18.

ORLANDO – Treating patients who developed myocardial injury after noncardiac surgery with the anticoagulant dabigatran significantly cut the rate of subsequent major vascular complications in a randomized, multicenter trial with 1,754 patients, a result that gives surgeons and physicians the first evidence-based intervention for treating a common postsurgical condition.

“Because we have not systematically followed noncardiac surgery patients, it’s easy to presume that everyone is okay, but all the epidemiology data show that these patients [who develop myocardial injury after noncardiac surgery] don’t do okay. We need to be aggressive with secondary prophylaxis,” P.J. Devereaux, MD, said at the annual meeting of the American College of Cardiology. “The unfortunate thing is that right now, we don’t do much for these patients,” said Dr. Devereaux, professor of medicine and director of cardiology at McMaster University in Hamilton, Ont.

Results from prior epidemiology studies have shown that, among the roughly 200 million patients who undergo noncardiac surgery worldwide each year, 8% will develop MINS (myocardial injury after noncardiac surgery) (Anesthesiology. 2014 March;120[3]:564-78). The myocardial injury that defines MINS is identified by either an overt MI that meets the universal definition, or an otherwise unexplained rise in serum troponin levels from baseline in the first couple of days after surgery. In the new study, Dr. Devereaux and his associates identified 80% of MINS by a troponin rise and 20% by a diagnosed MI.

The challenge in diagnosing MINS and then administering dabigatran will be implementation of this strategy into routine practice, commented Erin A. Bohula May, MD, a cardiologist at Brigham and Women’s Hospital in Boston. “The problem is, troponin is not routinely measured in postoperative patients. It will be hard to change practice,” she noted.

Dr. Devereaux agreed that a significant barrier is convincing clinicians, especially surgeons, to routinely measure a patient’s troponin levels just before and immediately after surgery. “People are lulled into a false sense of security because patients [who develop MINS] usually don’t have chest pain,” he said in a video interview. “When we first showed that patients with MINS have bad outcomes, that convinced some [surgeons] to measure troponin after surgery. “Showing we can do something about it” is another important step toward fostering more awareness of and interest in diagnosing and treating MINS.

The Management of Myocardial Injury After Noncardiac Surgery Trial (MANAGE) enrolled 1,754 patients at 82 centers in 19 countries. Researchers randomized patients to treatment with either 110 mg dabigatran b.i.d. or placebo. A majority of patients in both arms also received aspirin and a statin, treatments that Dr. Devereaux should be used along with dabigatran in routine practice, based on observational findings, although the efficacy of these drugs for MINS patients has not been tested in randomized studies. The study’s primary endpoint was the incidence of major vascular complications, a composite that included vascular mortality, nonfatal MI, nonfatal and nonhemorrhagic stroke, peripheral arterial thrombosis, amputation, or symptomatic venous thromboembolism.

After an average follow-up of 16 months, the primary endpoint occurred in 11% of the dabigatran-treated patients and in 15% of controls, which represented a 28% risk reduction that was statistically significant. The study’s primary safety endpoint was a composite of life-threatening, major, and critical organ bleeds, which occurred in 3% of the dabigatran-treated patients and in 4% of controls, a nonsignificant difference. The dabigatran-treated patients showed a significant excess of both minor bleeds – 15% compared with 10% in controls – and “nonsignificant” lower gastrointestinal bleeds, 4% with dabigatran and 1% in the controls. The dabigatran-treated patients also had a significantly higher incidence of dyspepsia.

MANAGE was funded by the Population Health Research Institute and had no commercial funding. Dr. Devereaux has received research support from Abbott Diagnostics, Boehringer Ingelheim, Philips Healthcare, and Roche Diagnostics. Dr. May has been a consultant to Daiichi Sankyo, Merck, and Servier and has received research funding from Eisai.

mzoler@frontlinemedcom.com

SOURCE: Devereaux P et al. ACC 18.

ORLANDO – Treating patients who developed myocardial injury after noncardiac surgery with the anticoagulant dabigatran significantly cut the rate of subsequent major vascular complications in a randomized, multicenter trial with 1,754 patients, a result that gives surgeons and physicians the first evidence-based intervention for treating a common postsurgical condition.

“Because we have not systematically followed noncardiac surgery patients, it’s easy to presume that everyone is okay, but all the epidemiology data show that these patients [who develop myocardial injury after noncardiac surgery] don’t do okay. We need to be aggressive with secondary prophylaxis,” P.J. Devereaux, MD, said at the annual meeting of the American College of Cardiology. “The unfortunate thing is that right now, we don’t do much for these patients,” said Dr. Devereaux, professor of medicine and director of cardiology at McMaster University in Hamilton, Ont.

Results from prior epidemiology studies have shown that, among the roughly 200 million patients who undergo noncardiac surgery worldwide each year, 8% will develop MINS (myocardial injury after noncardiac surgery) (Anesthesiology. 2014 March;120[3]:564-78). The myocardial injury that defines MINS is identified by either an overt MI that meets the universal definition, or an otherwise unexplained rise in serum troponin levels from baseline in the first couple of days after surgery. In the new study, Dr. Devereaux and his associates identified 80% of MINS by a troponin rise and 20% by a diagnosed MI.

The challenge in diagnosing MINS and then administering dabigatran will be implementation of this strategy into routine practice, commented Erin A. Bohula May, MD, a cardiologist at Brigham and Women’s Hospital in Boston. “The problem is, troponin is not routinely measured in postoperative patients. It will be hard to change practice,” she noted.

Dr. Devereaux agreed that a significant barrier is convincing clinicians, especially surgeons, to routinely measure a patient’s troponin levels just before and immediately after surgery. “People are lulled into a false sense of security because patients [who develop MINS] usually don’t have chest pain,” he said in a video interview. “When we first showed that patients with MINS have bad outcomes, that convinced some [surgeons] to measure troponin after surgery. “Showing we can do something about it” is another important step toward fostering more awareness of and interest in diagnosing and treating MINS.

The Management of Myocardial Injury After Noncardiac Surgery Trial (MANAGE) enrolled 1,754 patients at 82 centers in 19 countries. Researchers randomized patients to treatment with either 110 mg dabigatran b.i.d. or placebo. A majority of patients in both arms also received aspirin and a statin, treatments that Dr. Devereaux should be used along with dabigatran in routine practice, based on observational findings, although the efficacy of these drugs for MINS patients has not been tested in randomized studies. The study’s primary endpoint was the incidence of major vascular complications, a composite that included vascular mortality, nonfatal MI, nonfatal and nonhemorrhagic stroke, peripheral arterial thrombosis, amputation, or symptomatic venous thromboembolism.

After an average follow-up of 16 months, the primary endpoint occurred in 11% of the dabigatran-treated patients and in 15% of controls, which represented a 28% risk reduction that was statistically significant. The study’s primary safety endpoint was a composite of life-threatening, major, and critical organ bleeds, which occurred in 3% of the dabigatran-treated patients and in 4% of controls, a nonsignificant difference. The dabigatran-treated patients showed a significant excess of both minor bleeds – 15% compared with 10% in controls – and “nonsignificant” lower gastrointestinal bleeds, 4% with dabigatran and 1% in the controls. The dabigatran-treated patients also had a significantly higher incidence of dyspepsia.

MANAGE was funded by the Population Health Research Institute and had no commercial funding. Dr. Devereaux has received research support from Abbott Diagnostics, Boehringer Ingelheim, Philips Healthcare, and Roche Diagnostics. Dr. May has been a consultant to Daiichi Sankyo, Merck, and Servier and has received research funding from Eisai.

mzoler@frontlinemedcom.com

SOURCE: Devereaux P et al. ACC 18.

ORLANDO – The HeartMate 3 magnetically levitated left ventricular assist (LVAD) device provided far superior outcomes, compared with the widely used HeartMate II axial-flow pump at 2 years of follow-up in patients with advanced heart failure in the large multicenter MOMENTUM 3 trial, Mandeep R. Mehra, MD, reported at the annual meeting of the American College of Cardiology.

Bruce Jancin/Frontline Medical News

HeartMate 3 recipients had a 90% lower risk of undergoing reoperation to replace or remove their device because of malfunction, and a stroke rate half that in the HeartMate II group.

“This was the lowest rate of stroke ever seen in any LVAD trial,” according to Dr. Mehra, medical director of the Brigham and Women’s Hospital Heart and Vascular Center, Boston, and professor of medicine at Harvard Medical School.

“We believe this is a practice-changing result in the field, and that the real implication of our findings is to reassure those who refer or treat patients with advanced heart failure that it is perhaps going to be ignorant not to refer patients for consideration for destination therapy,” he said at a press conference highlighting the MOMENTUM 3 results, also presented in a late-breaking clinical trials session.

The HeartMate 3 is a miniaturized centrifugal-flow device that fits entirely within the chest, whereas the HeartMate II requires creation of a pocket in the abdomen. The HeartMate 3 was designed to prevent pump thrombosis – a common limiting problem with the HeartMate II and other LVADs – by employing three innovations: use of wide blood-flow passages to reduce shear stress and minimize disruption of red blood cells as they pass through the pump; reliance on magnetic levitation technology to create a frictionless pump with no mechanical bearings, which are subject to wear and tear; and incorporation of an artificial fixed pulse that speeds up and slows every 2 seconds in order to minimize blood stasis, which promotes thrombosis, the cardiologist explained in a video interview.

Bruce Jancin/Frontline Medical News

Discussant James L. Janzuzzi Jr., called the MOMENTUM 3 results “a very-much-needed step forward.”

bjancin@frontlinemedcom.com

SOURCE: Mehra M et al. ACC 18.

ORLANDO – The HeartMate 3 magnetically levitated left ventricular assist (LVAD) device provided far superior outcomes, compared with the widely used HeartMate II axial-flow pump at 2 years of follow-up in patients with advanced heart failure in the large multicenter MOMENTUM 3 trial, Mandeep R. Mehra, MD, reported at the annual meeting of the American College of Cardiology.

Bruce Jancin/Frontline Medical News

HeartMate 3 recipients had a 90% lower risk of undergoing reoperation to replace or remove their device because of malfunction, and a stroke rate half that in the HeartMate II group.

“This was the lowest rate of stroke ever seen in any LVAD trial,” according to Dr. Mehra, medical director of the Brigham and Women’s Hospital Heart and Vascular Center, Boston, and professor of medicine at Harvard Medical School.

“We believe this is a practice-changing result in the field, and that the real implication of our findings is to reassure those who refer or treat patients with advanced heart failure that it is perhaps going to be ignorant not to refer patients for consideration for destination therapy,” he said at a press conference highlighting the MOMENTUM 3 results, also presented in a late-breaking clinical trials session.

The HeartMate 3 is a miniaturized centrifugal-flow device that fits entirely within the chest, whereas the HeartMate II requires creation of a pocket in the abdomen. The HeartMate 3 was designed to prevent pump thrombosis – a common limiting problem with the HeartMate II and other LVADs – by employing three innovations: use of wide blood-flow passages to reduce shear stress and minimize disruption of red blood cells as they pass through the pump; reliance on magnetic levitation technology to create a frictionless pump with no mechanical bearings, which are subject to wear and tear; and incorporation of an artificial fixed pulse that speeds up and slows every 2 seconds in order to minimize blood stasis, which promotes thrombosis, the cardiologist explained in a video interview.

Bruce Jancin/Frontline Medical News

Discussant James L. Janzuzzi Jr., called the MOMENTUM 3 results “a very-much-needed step forward.”

bjancin@frontlinemedcom.com

SOURCE: Mehra M et al. ACC 18.

ORLANDO – The HeartMate 3 magnetically levitated left ventricular assist (LVAD) device provided far superior outcomes, compared with the widely used HeartMate II axial-flow pump at 2 years of follow-up in patients with advanced heart failure in the large multicenter MOMENTUM 3 trial, Mandeep R. Mehra, MD, reported at the annual meeting of the American College of Cardiology.

Bruce Jancin/Frontline Medical News

HeartMate 3 recipients had a 90% lower risk of undergoing reoperation to replace or remove their device because of malfunction, and a stroke rate half that in the HeartMate II group.

“This was the lowest rate of stroke ever seen in any LVAD trial,” according to Dr. Mehra, medical director of the Brigham and Women’s Hospital Heart and Vascular Center, Boston, and professor of medicine at Harvard Medical School.

“We believe this is a practice-changing result in the field, and that the real implication of our findings is to reassure those who refer or treat patients with advanced heart failure that it is perhaps going to be ignorant not to refer patients for consideration for destination therapy,” he said at a press conference highlighting the MOMENTUM 3 results, also presented in a late-breaking clinical trials session.

The HeartMate 3 is a miniaturized centrifugal-flow device that fits entirely within the chest, whereas the HeartMate II requires creation of a pocket in the abdomen. The HeartMate 3 was designed to prevent pump thrombosis – a common limiting problem with the HeartMate II and other LVADs – by employing three innovations: use of wide blood-flow passages to reduce shear stress and minimize disruption of red blood cells as they pass through the pump; reliance on magnetic levitation technology to create a frictionless pump with no mechanical bearings, which are subject to wear and tear; and incorporation of an artificial fixed pulse that speeds up and slows every 2 seconds in order to minimize blood stasis, which promotes thrombosis, the cardiologist explained in a video interview.

Bruce Jancin/Frontline Medical News

Discussant James L. Janzuzzi Jr., called the MOMENTUM 3 results “a very-much-needed step forward.”

bjancin@frontlinemedcom.com

SOURCE: Mehra M et al. ACC 18.

Closer tailoring might boost wearable cardioverter defibrillators’ benefit, alirocumab cuts deaths in post–acute coronary syndrome patients, the ODYSSEY Outcomes trial redefines secondary cardiovascular prevention, and how walking cuts postmenopausal women’s heart failure risk.

Listen to the MDedge Daily News podcast for all the details on today’s top news.


 

Closer tailoring might boost wearable cardioverter defibrillators’ benefit, alirocumab cuts deaths in post–acute coronary syndrome patients, the ODYSSEY Outcomes trial redefines secondary cardiovascular prevention, and how walking cuts postmenopausal women’s heart failure risk.

Listen to the MDedge Daily News podcast for all the details on today’s top news.


 

Closer tailoring might boost wearable cardioverter defibrillators’ benefit, alirocumab cuts deaths in post–acute coronary syndrome patients, the ODYSSEY Outcomes trial redefines secondary cardiovascular prevention, and how walking cuts postmenopausal women’s heart failure risk.

Listen to the MDedge Daily News podcast for all the details on today’s top news.


 

Evacetrapib missed its primary MACE endpoint compared with placebo among patients with high-risk vascular disease, including those who were homozygous (AA) for polymorphism rs1967309 of the ADCY gene, in a large nested case-control analysis of the ACCELERATE trial.
The results contradict those for another cholesteryl ester transfer protein (CETP) inhibitor – dalcetrapib –  which has shown significant cardiovascular benefits only among AA patients.

“Although directionally similar to the dalcetrapib analysis, there was no significant interaction between genotype and cardiovascular outcome with evacetrapib,” Steven E. Nissen, MD, and his associates wrote simultaneously in JAMA Cardiology and reported at the annual meeting of the American College of Cardiology.

Four CETP inhibitors have reached full-scale development: evacetrapib, dalcetrapib, torcetrapib, and anacetrapib. They all markedly increase circulating HDL, and all except dalcetrapib cut circulating LDL. But those benefits largely haven’t extended to the key endpoint, major adverse cardiovascular events (MACE). In large trials, torcetrapib increased MACE, anacetrapib reduced MACE by such a small amount that its maker did not file for FDA approval, and evacetrapib and dalcetrapib had no effect on MACE. 

But there was a caveat for dalcetrapib. In a post-hoc analysis of its placebo-controlled trial, the CETP inhibitor reduced MACE by 39% among AA individuals and increased MACE by 27% among GG individuals, those homozygous negative for the SNP rs1967309. 

These findings could make sense because ADCY gene variants have been linked to carotid intimal medial thickness, high-sensitivity C-reactive protein, and cholesterol efflux capacity, wrote Dr. Nissen of the department of cardiovascular medicine, Cleveland Clinic, Cleveland, Ohio (JAMA Cardiol. 2018 Mar 11. doi: 10.1001/jamacardio.2018.0569). 

To explore whether ADCY genotypep also affects evacetrapib response, he and his associates compared 1,427 cases with MACE with 1,532 matched controls from the international, randomized, double-blind ACCELERATE (Assessment of Clinical Effects of Cholesteryl Ester Transfer Protein Inhibition with Evacetrapib in Patients at a High Risk for Vascular Outcomes) trial (NCT01687998). Participants had cerebrovascular atherosclerotic disease, peripheral arterial disease, coronary artery disease with diabetes, or recent acute coronary syndrome. They received oral evacetrapib (130 mg) or placebo, and the primary endpoint was a composite of cardiovascular death, myocardial infarction, stroke, coronary revascularization, or hospitalization for unstable angina.

Evacetrapib missed this primary endpoint in all genetic subgroups. Odds ratios for evacetrapib compared with placebo were 0.88 (95% confidence interval, 0.69 to 1.12) among AA patients, 1.04 (95% CI, 0.90 to 1.21) among heterozygous (AG) patients, and 1.18 (95% CI, 0.98 to 1.41) among GG patients. A test for interaction also was insignificant (P = .17). A test for trend nearly reached significance (P = .06), but weakened when the investigators controlled for cardiovascular risk factors or looked only at hard cardiovascular outcomes, they said.

Thus, the relationship between evacetrapib response and AA genotype “was far less in magnitude than observed in the pharmacogenetic study with dalcetrapib,” they wrote. Dalcetrapib is a weaker CETP inhibitor than evacetrapib, the study populations weren’t identical, and the trials used different statistical methods, all of which could explain the discrepant findings, they added. “The completion of the dalcetrapib pharmacogenetics outcome trial should clarify whether this is a false signal or a paradigm-shifting discovery.”

Eli Lilly provided funding, helped design and conduct the study, and helped write the manuscript. Dr. Nissen reported receiving grants and nonfinancial support from Eli Lilly while conducting the study. Several coinvestigators also disclosed ties to Eli Lilly and six reported being employees of the company.

Source: JAMA Cardiol. doi:10.1001/jamacardio.2018.0569.

Evacetrapib missed its primary MACE endpoint compared with placebo among patients with high-risk vascular disease, including those who were homozygous (AA) for polymorphism rs1967309 of the ADCY gene, in a large nested case-control analysis of the ACCELERATE trial.
The results contradict those for another cholesteryl ester transfer protein (CETP) inhibitor – dalcetrapib –  which has shown significant cardiovascular benefits only among AA patients.

“Although directionally similar to the dalcetrapib analysis, there was no significant interaction between genotype and cardiovascular outcome with evacetrapib,” Steven E. Nissen, MD, and his associates wrote simultaneously in JAMA Cardiology and reported at the annual meeting of the American College of Cardiology.

Four CETP inhibitors have reached full-scale development: evacetrapib, dalcetrapib, torcetrapib, and anacetrapib. They all markedly increase circulating HDL, and all except dalcetrapib cut circulating LDL. But those benefits largely haven’t extended to the key endpoint, major adverse cardiovascular events (MACE). In large trials, torcetrapib increased MACE, anacetrapib reduced MACE by such a small amount that its maker did not file for FDA approval, and evacetrapib and dalcetrapib had no effect on MACE. 

But there was a caveat for dalcetrapib. In a post-hoc analysis of its placebo-controlled trial, the CETP inhibitor reduced MACE by 39% among AA individuals and increased MACE by 27% among GG individuals, those homozygous negative for the SNP rs1967309. 

These findings could make sense because ADCY gene variants have been linked to carotid intimal medial thickness, high-sensitivity C-reactive protein, and cholesterol efflux capacity, wrote Dr. Nissen of the department of cardiovascular medicine, Cleveland Clinic, Cleveland, Ohio (JAMA Cardiol. 2018 Mar 11. doi: 10.1001/jamacardio.2018.0569). 

To explore whether ADCY genotypep also affects evacetrapib response, he and his associates compared 1,427 cases with MACE with 1,532 matched controls from the international, randomized, double-blind ACCELERATE (Assessment of Clinical Effects of Cholesteryl Ester Transfer Protein Inhibition with Evacetrapib in Patients at a High Risk for Vascular Outcomes) trial (NCT01687998). Participants had cerebrovascular atherosclerotic disease, peripheral arterial disease, coronary artery disease with diabetes, or recent acute coronary syndrome. They received oral evacetrapib (130 mg) or placebo, and the primary endpoint was a composite of cardiovascular death, myocardial infarction, stroke, coronary revascularization, or hospitalization for unstable angina.

Evacetrapib missed this primary endpoint in all genetic subgroups. Odds ratios for evacetrapib compared with placebo were 0.88 (95% confidence interval, 0.69 to 1.12) among AA patients, 1.04 (95% CI, 0.90 to 1.21) among heterozygous (AG) patients, and 1.18 (95% CI, 0.98 to 1.41) among GG patients. A test for interaction also was insignificant (P = .17). A test for trend nearly reached significance (P = .06), but weakened when the investigators controlled for cardiovascular risk factors or looked only at hard cardiovascular outcomes, they said.

Thus, the relationship between evacetrapib response and AA genotype “was far less in magnitude than observed in the pharmacogenetic study with dalcetrapib,” they wrote. Dalcetrapib is a weaker CETP inhibitor than evacetrapib, the study populations weren’t identical, and the trials used different statistical methods, all of which could explain the discrepant findings, they added. “The completion of the dalcetrapib pharmacogenetics outcome trial should clarify whether this is a false signal or a paradigm-shifting discovery.”

Eli Lilly provided funding, helped design and conduct the study, and helped write the manuscript. Dr. Nissen reported receiving grants and nonfinancial support from Eli Lilly while conducting the study. Several coinvestigators also disclosed ties to Eli Lilly and six reported being employees of the company.

Source: JAMA Cardiol. doi:10.1001/jamacardio.2018.0569.

Evacetrapib missed its primary MACE endpoint compared with placebo among patients with high-risk vascular disease, including those who were homozygous (AA) for polymorphism rs1967309 of the ADCY gene, in a large nested case-control analysis of the ACCELERATE trial.
The results contradict those for another cholesteryl ester transfer protein (CETP) inhibitor – dalcetrapib –  which has shown significant cardiovascular benefits only among AA patients.

“Although directionally similar to the dalcetrapib analysis, there was no significant interaction between genotype and cardiovascular outcome with evacetrapib,” Steven E. Nissen, MD, and his associates wrote simultaneously in JAMA Cardiology and reported at the annual meeting of the American College of Cardiology.

Four CETP inhibitors have reached full-scale development: evacetrapib, dalcetrapib, torcetrapib, and anacetrapib. They all markedly increase circulating HDL, and all except dalcetrapib cut circulating LDL. But those benefits largely haven’t extended to the key endpoint, major adverse cardiovascular events (MACE). In large trials, torcetrapib increased MACE, anacetrapib reduced MACE by such a small amount that its maker did not file for FDA approval, and evacetrapib and dalcetrapib had no effect on MACE. 

But there was a caveat for dalcetrapib. In a post-hoc analysis of its placebo-controlled trial, the CETP inhibitor reduced MACE by 39% among AA individuals and increased MACE by 27% among GG individuals, those homozygous negative for the SNP rs1967309. 

These findings could make sense because ADCY gene variants have been linked to carotid intimal medial thickness, high-sensitivity C-reactive protein, and cholesterol efflux capacity, wrote Dr. Nissen of the department of cardiovascular medicine, Cleveland Clinic, Cleveland, Ohio (JAMA Cardiol. 2018 Mar 11. doi: 10.1001/jamacardio.2018.0569). 

To explore whether ADCY genotypep also affects evacetrapib response, he and his associates compared 1,427 cases with MACE with 1,532 matched controls from the international, randomized, double-blind ACCELERATE (Assessment of Clinical Effects of Cholesteryl Ester Transfer Protein Inhibition with Evacetrapib in Patients at a High Risk for Vascular Outcomes) trial (NCT01687998). Participants had cerebrovascular atherosclerotic disease, peripheral arterial disease, coronary artery disease with diabetes, or recent acute coronary syndrome. They received oral evacetrapib (130 mg) or placebo, and the primary endpoint was a composite of cardiovascular death, myocardial infarction, stroke, coronary revascularization, or hospitalization for unstable angina.

Evacetrapib missed this primary endpoint in all genetic subgroups. Odds ratios for evacetrapib compared with placebo were 0.88 (95% confidence interval, 0.69 to 1.12) among AA patients, 1.04 (95% CI, 0.90 to 1.21) among heterozygous (AG) patients, and 1.18 (95% CI, 0.98 to 1.41) among GG patients. A test for interaction also was insignificant (P = .17). A test for trend nearly reached significance (P = .06), but weakened when the investigators controlled for cardiovascular risk factors or looked only at hard cardiovascular outcomes, they said.

Thus, the relationship between evacetrapib response and AA genotype “was far less in magnitude than observed in the pharmacogenetic study with dalcetrapib,” they wrote. Dalcetrapib is a weaker CETP inhibitor than evacetrapib, the study populations weren’t identical, and the trials used different statistical methods, all of which could explain the discrepant findings, they added. “The completion of the dalcetrapib pharmacogenetics outcome trial should clarify whether this is a false signal or a paradigm-shifting discovery.”

Eli Lilly provided funding, helped design and conduct the study, and helped write the manuscript. Dr. Nissen reported receiving grants and nonfinancial support from Eli Lilly while conducting the study. Several coinvestigators also disclosed ties to Eli Lilly and six reported being employees of the company.

Source: JAMA Cardiol. doi:10.1001/jamacardio.2018.0569.

ORLANDO – Anthracycline chemotherapy was associated with a cardiotoxicity incidence of roughly 14% of breast cancer patients regardless of treatment with carvedilol, based on data from a randomized trial of 200 patients.

“Cardio-oncology has been neglected,” Monica Samuel Avila, MD, of Hospital das Clínicas da Faculdade de Medicina da Universidade in São Paulo, Brazil, said in a video interview at the annual meeting of the American College of Cardiology. “We have seen improvement of survival in patients with cancer, but with that comes complications related to treatment. I think that the interactions between cardiologists and oncologists are increasing in a more important way,” she said.

In the Carvedilol for Prevention of Chemotherapy-Induced Cardiotoxicity (CECCY) Trial, Dr. Avila and colleagues evaluated primary prevention of cardiotoxicity in women with normal hearts who were undergoing chemotherapy for breast cancer.

SOURCE: Avila, M. ACC 18

ORLANDO – Anthracycline chemotherapy was associated with a cardiotoxicity incidence of roughly 14% of breast cancer patients regardless of treatment with carvedilol, based on data from a randomized trial of 200 patients.

“Cardio-oncology has been neglected,” Monica Samuel Avila, MD, of Hospital das Clínicas da Faculdade de Medicina da Universidade in São Paulo, Brazil, said in a video interview at the annual meeting of the American College of Cardiology. “We have seen improvement of survival in patients with cancer, but with that comes complications related to treatment. I think that the interactions between cardiologists and oncologists are increasing in a more important way,” she said.

In the Carvedilol for Prevention of Chemotherapy-Induced Cardiotoxicity (CECCY) Trial, Dr. Avila and colleagues evaluated primary prevention of cardiotoxicity in women with normal hearts who were undergoing chemotherapy for breast cancer.

SOURCE: Avila, M. ACC 18

ORLANDO – Anthracycline chemotherapy was associated with a cardiotoxicity incidence of roughly 14% of breast cancer patients regardless of treatment with carvedilol, based on data from a randomized trial of 200 patients.

“Cardio-oncology has been neglected,” Monica Samuel Avila, MD, of Hospital das Clínicas da Faculdade de Medicina da Universidade in São Paulo, Brazil, said in a video interview at the annual meeting of the American College of Cardiology. “We have seen improvement of survival in patients with cancer, but with that comes complications related to treatment. I think that the interactions between cardiologists and oncologists are increasing in a more important way,” she said.

In the Carvedilol for Prevention of Chemotherapy-Induced Cardiotoxicity (CECCY) Trial, Dr. Avila and colleagues evaluated primary prevention of cardiotoxicity in women with normal hearts who were undergoing chemotherapy for breast cancer.

SOURCE: Avila, M. ACC 18

For patients under age 75 years with ST-segment elevation myocardial infarction, switching from clopidogrel to ticagrelor was noninferior to continuing clopidogrel in terms of 30-day rates of major bleeding, investigators reported at the annual meeting of the American College of Cardiology.

Catherine Hackett/Frontline Medical News

Rates of thrombolysis in myocardial infarction (TIMI) major bleeding through 30 days were 0.73% in the ticagrelor group and 0.69% in the clopidogrel group, for an absolute difference of 0.04% (95% confidence interval, −0.49% to 0.58%; P less than .001 for noninferiority). “However, minor bleeding was increased with ticagrelor, and there was no benefit on efficacy outcomes,” Otavio Berwanger, MD, PhD, wrote simultaneously in JAMA Cardiology, on behalf of the writing committee for the randomized, phase 3, open-label TREAT trial.

Abundant, robust data support prompt revascularization in ST-elevation myocardial infarction (STEMI), but the real world doesn’t always meet this standard, and lytics remain in wide use in many countries, noted Dr. Berwanger, Director of the Research Institute at the Heart Hospital of Sao Paulo (Brazil). In the early 2000s, two large trials showed that dual antiplatelet therapy with aspirin and clopidogrel reduced major adverse cardiovascular events in patients receiving fibrinolytics for STEMI. More recently, the Platelet Inhibition and Patient Outcomes (PLATO) study favored ticagrelor over clopidogrel for reducing cardiovascular or stroke-related death, with no increase in the risk of major bleeding, despite ticagrelor’s boxed warning.  

However, PLATO excluded patients who received fibrinolytics in the 24 hours before treatment because of concerns that ticagrelor might contribute to serious or fatal bleeding. To assess this risk, Dr. Berwanger and his associates from 10 countries randomly assigned 3,799 patients with STEMI to receive either ticagrelor (180-mg loading dose; 90 mg twice daily thereafter) or clopidogrel (300-mg to 600-mg loading dose; 75 mg daily thereafter) a median of 11.4 hours after fibrinolysis. Patients averaged 58 years in age (standard deviation, 9.5 years), 77% were men, and 57% were white. 

Because about 90% of patients had been pretreated with clopidogrel, the study primarily compared the effect of staying on clopidogrel with switching to ticagrelor, the investigators noted. “Our trial was an investigator- initiated trial with limited funding that did not allow a double-dummy design,” they added. “We attempted to minimize the risk of bias associated with the open-label nature of the study by performing blinded outcome adjudication.”

In terms of secondary endpoints, 23 patients (1.2%) on ticagrelor developed major bleeding according to PLATO criteria and Bleeding Academic Research Consortium (BARC) criteria, as did 26 patients (1.4%) on clopidogrel at 30-day follow-up (absolute difference, −0.18%; 95% CI, −0.89% to 0.54; P = .001 for noninferiority). Ticagrelor and clopidogrel also resembled each other in terms of fatal bleeds (0.16% versus 0.11%, respectively; P = .67) and intracranial bleeds (0.42% versus 0.37%; P = .82).

However, minimal PLATO bleeding was significantly more common with ticagrelor (3.2%) than with clopidogrel (2%; P = .02), the researchers reported. Clinically significant TIMI bleeding requiring medical attention occurred in 2% of the ticagrelor group and 1.2% of the clopidogrel group (P = .06), and ticagrelor was no more effective than clopidogrel in terms of preventing death from vascular causes, myocardial infarction, or stroke, with a composite rate of 4% in each arm and a statistically insignificant hazard ratio of (0.91; 95% CI, 0.67 to 1.25; P = .57). 

Additionally, while similar proportions of patients stopped treatment because of adverse events, dyspnea was more common with ticagrelor (13.9%) than clopidogrel (7.6%). “Based on our findings, patients with STEMI younger than 75 years who initially received clopidogrel can be safely switched to ticagrelor in the first 24 hours after fibrinolysis,” the researchers wrote. “Whether this strategy will result in fewer cardiovascular events in the long term remains to be determined.”

AstraZeneca makes ticagrelor and funded the trial. Dr. Berwanger disclosed grants and personal fees from AstraZeneca and several other pharmaceutical companies.

Source: JAMA Cardiol. doi:10.1001/jamacardio.2018.0612

For patients under age 75 years with ST-segment elevation myocardial infarction, switching from clopidogrel to ticagrelor was noninferior to continuing clopidogrel in terms of 30-day rates of major bleeding, investigators reported at the annual meeting of the American College of Cardiology.

Catherine Hackett/Frontline Medical News

Rates of thrombolysis in myocardial infarction (TIMI) major bleeding through 30 days were 0.73% in the ticagrelor group and 0.69% in the clopidogrel group, for an absolute difference of 0.04% (95% confidence interval, −0.49% to 0.58%; P less than .001 for noninferiority). “However, minor bleeding was increased with ticagrelor, and there was no benefit on efficacy outcomes,” Otavio Berwanger, MD, PhD, wrote simultaneously in JAMA Cardiology, on behalf of the writing committee for the randomized, phase 3, open-label TREAT trial.

Abundant, robust data support prompt revascularization in ST-elevation myocardial infarction (STEMI), but the real world doesn’t always meet this standard, and lytics remain in wide use in many countries, noted Dr. Berwanger, Director of the Research Institute at the Heart Hospital of Sao Paulo (Brazil). In the early 2000s, two large trials showed that dual antiplatelet therapy with aspirin and clopidogrel reduced major adverse cardiovascular events in patients receiving fibrinolytics for STEMI. More recently, the Platelet Inhibition and Patient Outcomes (PLATO) study favored ticagrelor over clopidogrel for reducing cardiovascular or stroke-related death, with no increase in the risk of major bleeding, despite ticagrelor’s boxed warning.  

However, PLATO excluded patients who received fibrinolytics in the 24 hours before treatment because of concerns that ticagrelor might contribute to serious or fatal bleeding. To assess this risk, Dr. Berwanger and his associates from 10 countries randomly assigned 3,799 patients with STEMI to receive either ticagrelor (180-mg loading dose; 90 mg twice daily thereafter) or clopidogrel (300-mg to 600-mg loading dose; 75 mg daily thereafter) a median of 11.4 hours after fibrinolysis. Patients averaged 58 years in age (standard deviation, 9.5 years), 77% were men, and 57% were white. 

Because about 90% of patients had been pretreated with clopidogrel, the study primarily compared the effect of staying on clopidogrel with switching to ticagrelor, the investigators noted. “Our trial was an investigator- initiated trial with limited funding that did not allow a double-dummy design,” they added. “We attempted to minimize the risk of bias associated with the open-label nature of the study by performing blinded outcome adjudication.”

In terms of secondary endpoints, 23 patients (1.2%) on ticagrelor developed major bleeding according to PLATO criteria and Bleeding Academic Research Consortium (BARC) criteria, as did 26 patients (1.4%) on clopidogrel at 30-day follow-up (absolute difference, −0.18%; 95% CI, −0.89% to 0.54; P = .001 for noninferiority). Ticagrelor and clopidogrel also resembled each other in terms of fatal bleeds (0.16% versus 0.11%, respectively; P = .67) and intracranial bleeds (0.42% versus 0.37%; P = .82).

However, minimal PLATO bleeding was significantly more common with ticagrelor (3.2%) than with clopidogrel (2%; P = .02), the researchers reported. Clinically significant TIMI bleeding requiring medical attention occurred in 2% of the ticagrelor group and 1.2% of the clopidogrel group (P = .06), and ticagrelor was no more effective than clopidogrel in terms of preventing death from vascular causes, myocardial infarction, or stroke, with a composite rate of 4% in each arm and a statistically insignificant hazard ratio of (0.91; 95% CI, 0.67 to 1.25; P = .57). 

Additionally, while similar proportions of patients stopped treatment because of adverse events, dyspnea was more common with ticagrelor (13.9%) than clopidogrel (7.6%). “Based on our findings, patients with STEMI younger than 75 years who initially received clopidogrel can be safely switched to ticagrelor in the first 24 hours after fibrinolysis,” the researchers wrote. “Whether this strategy will result in fewer cardiovascular events in the long term remains to be determined.”

AstraZeneca makes ticagrelor and funded the trial. Dr. Berwanger disclosed grants and personal fees from AstraZeneca and several other pharmaceutical companies.

Source: JAMA Cardiol. doi:10.1001/jamacardio.2018.0612

For patients under age 75 years with ST-segment elevation myocardial infarction, switching from clopidogrel to ticagrelor was noninferior to continuing clopidogrel in terms of 30-day rates of major bleeding, investigators reported at the annual meeting of the American College of Cardiology.

Catherine Hackett/Frontline Medical News

Rates of thrombolysis in myocardial infarction (TIMI) major bleeding through 30 days were 0.73% in the ticagrelor group and 0.69% in the clopidogrel group, for an absolute difference of 0.04% (95% confidence interval, −0.49% to 0.58%; P less than .001 for noninferiority). “However, minor bleeding was increased with ticagrelor, and there was no benefit on efficacy outcomes,” Otavio Berwanger, MD, PhD, wrote simultaneously in JAMA Cardiology, on behalf of the writing committee for the randomized, phase 3, open-label TREAT trial.

Abundant, robust data support prompt revascularization in ST-elevation myocardial infarction (STEMI), but the real world doesn’t always meet this standard, and lytics remain in wide use in many countries, noted Dr. Berwanger, Director of the Research Institute at the Heart Hospital of Sao Paulo (Brazil). In the early 2000s, two large trials showed that dual antiplatelet therapy with aspirin and clopidogrel reduced major adverse cardiovascular events in patients receiving fibrinolytics for STEMI. More recently, the Platelet Inhibition and Patient Outcomes (PLATO) study favored ticagrelor over clopidogrel for reducing cardiovascular or stroke-related death, with no increase in the risk of major bleeding, despite ticagrelor’s boxed warning.  

However, PLATO excluded patients who received fibrinolytics in the 24 hours before treatment because of concerns that ticagrelor might contribute to serious or fatal bleeding. To assess this risk, Dr. Berwanger and his associates from 10 countries randomly assigned 3,799 patients with STEMI to receive either ticagrelor (180-mg loading dose; 90 mg twice daily thereafter) or clopidogrel (300-mg to 600-mg loading dose; 75 mg daily thereafter) a median of 11.4 hours after fibrinolysis. Patients averaged 58 years in age (standard deviation, 9.5 years), 77% were men, and 57% were white. 

Because about 90% of patients had been pretreated with clopidogrel, the study primarily compared the effect of staying on clopidogrel with switching to ticagrelor, the investigators noted. “Our trial was an investigator- initiated trial with limited funding that did not allow a double-dummy design,” they added. “We attempted to minimize the risk of bias associated with the open-label nature of the study by performing blinded outcome adjudication.”

In terms of secondary endpoints, 23 patients (1.2%) on ticagrelor developed major bleeding according to PLATO criteria and Bleeding Academic Research Consortium (BARC) criteria, as did 26 patients (1.4%) on clopidogrel at 30-day follow-up (absolute difference, −0.18%; 95% CI, −0.89% to 0.54; P = .001 for noninferiority). Ticagrelor and clopidogrel also resembled each other in terms of fatal bleeds (0.16% versus 0.11%, respectively; P = .67) and intracranial bleeds (0.42% versus 0.37%; P = .82).

However, minimal PLATO bleeding was significantly more common with ticagrelor (3.2%) than with clopidogrel (2%; P = .02), the researchers reported. Clinically significant TIMI bleeding requiring medical attention occurred in 2% of the ticagrelor group and 1.2% of the clopidogrel group (P = .06), and ticagrelor was no more effective than clopidogrel in terms of preventing death from vascular causes, myocardial infarction, or stroke, with a composite rate of 4% in each arm and a statistically insignificant hazard ratio of (0.91; 95% CI, 0.67 to 1.25; P = .57). 

Additionally, while similar proportions of patients stopped treatment because of adverse events, dyspnea was more common with ticagrelor (13.9%) than clopidogrel (7.6%). “Based on our findings, patients with STEMI younger than 75 years who initially received clopidogrel can be safely switched to ticagrelor in the first 24 hours after fibrinolysis,” the researchers wrote. “Whether this strategy will result in fewer cardiovascular events in the long term remains to be determined.”

AstraZeneca makes ticagrelor and funded the trial. Dr. Berwanger disclosed grants and personal fees from AstraZeneca and several other pharmaceutical companies.

Source: JAMA Cardiol. doi:10.1001/jamacardio.2018.0612

ORLANDO – In what was hailed as a major advance in preventive cardiology, the ODYSSEY Outcomes trial has shown that adding the PCSK9 inhibitor alirocumab on top of intensive statin therapy reduced major adverse cardiovascular events and all-cause mortality significantly more than placebo plus intensive statin therapy in patients with a recent acute coronary syndrome and an elevated on-statin LDL cholesterol level. 

Bruce Jancin/Frontline Medical News

ODYSSEY Outcomes was a double-blind trial in which 18,924 patients at 1,315 sites in 57 countries were randomized to alirocumab (Praluent) or placebo plus background high-intensity statin therapy starting a median of 2.5 months after an acute coronary syndrome. All participants had to have a baseline LDL cholesterol level of 70 mg/dL or higher despite intensive statin therapy. Alirocumab was titrated to maintain a target LDL of 25-50 mg/dL. An LDL of 15-25 mg/dL was deemed acceptable, but if the level dropped below 15 mg/dL on two consecutive measurements the patient was blindly switched to placebo, as occurred in 7.7% of the alirocumab group. 

The primary study endpoint was a composite outcome comprised of CHD (coronary heart disease) death, nonfatal MI, ischemic stroke, or unstable angina requiring hospitalization. During a median 2.8 years of follow-up, this outcome occurred in 9.5% of the overall population randomized to alirocumab and 11.1% of those on placebo, for a statistically significant and clinically meaningful 15% reduction in relative risk. The CHD death rates in the two study arms were similar; however, the other three components of the primary endpoint occurred significantly less often in the alirocumab group: The risk of nonfatal MI was 14% less (6.6% vs. 7.6%), ischemic stroke was 27% less (1.2 vs. 1.6%), and unstable angina was 39% less (0.4% vs. 0.6%).

All-cause mortality occurred in 3.5% of patients receiving alirocumab and 4.1% on placebo, once again for a statistically significant 15% reduction in risk. This was a major achievement, since even statins haven’t shown a mortality benefit in the post-ACS setting, observed Dr. Steg, cochair of the study. 

The greatest benefits were seen in the 5,629 participants with a baseline LDL of 100 mg/dL or more on high-intensity statin therapy. In this large subgroup at highest baseline risk, alirocumab resulted in an absolute 3.4% risk reduction and a 24% reduction in relative risk of MACE. All-cause mortality decreased by an absolute 1.7%, translating to a 29% relative risk reduction. The number-needed-to-treat (NNT) for the duration of the study in order to prevent one additional MACE event in this group was 29, with an NNT to prevent one additional death of 60, added Dr. Steg, professor of cardiology at the University of Paris and chief of cardiology at Bichat Hospital. 

“The risk/benefit for alirocumab is extraordinarily favorable. There was almost no risk over the course of the trial. There was no increase in neurocognitive disorders, new-onset or worsening diabetes, cataracts, or hemorrhagic stroke,” the cardiologist said. 
Indeed, the sole adverse event that occurred more frequently in the alirocumab group was mild local injection site reactions, which occurred in 3.8% of the alirocumab group and 2.1% of controls. 

There was a tendency for LDL to creep upward in both the alirocumab and placebo arms over the course of follow-up. Dr. Steg attributed this to down-titration or cessation of alirocumab as per protocol along with the inability of a substantial proportion of patients to tolerate intensive statin therapy. Most study participants had never been on a statin until their ACS. 

A year ago at ACC 2017, other investigators presented the results of FOURIER, a large clinical outcomes trial of evolocumab (Repatha), another PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitor. FOURIER also showed a 15% relative risk reduction in major adverse cardiovascular events, but unlike in ODYSSEY Outcomes, there was no significant impact upon mortality. Dr. Steg attributed this to several key differences between the two trials.

The post-ACS population of ODYSSEY Outcomes was on average higher-risk than FOURIER participants, who had stable atherosclerotic cardiovascular disease. The background statin therapy was more intensive in ODYSSEY, and the average follow-up was close to 8 months longer, too. 

Bruce Jancin/Frontline Medical News

The study population is representative of an enormous number of patients seen in clinical practice, added Dr. Fuster, professor of medicine and physician-in-chief at Mount Sinai Hospital in New York. He estimated that one-third of patients who experience ACS can’t subsequently get their LDL down to the 70 mg/dL range on statin therapy, generally because of drug intolerance. 
He voiced a concern: “Up until now, the feasibility and affordability of using this type of drug has been extremely difficult. I hope this particular study is a trigger – a catalyzer – for making this drug much more available to people who need it.” 

The study met with an enthusiastic audience reception. Prior to presentation of the results at the meeting’s opening session, 79% of the audience of more than 4,000 in the main arena indicated they either don’t prescribe PCSK9 inhibitors or do so only a handful of times per year.

Immediately after seeing the data, 62% of the audience said their practice will change as a result of the study findings. 

ODYSSEY Outcomes was funded by Sanofi and Regeneron Pharmaceuticals. Dr. Steg reported serving as a consultant to and receiving research grants from those pharmaceutical companies and numerous others. 

bjancin@frontlinemedcom.com 
SOURCE: Steg GP. 

ORLANDO – In what was hailed as a major advance in preventive cardiology, the ODYSSEY Outcomes trial has shown that adding the PCSK9 inhibitor alirocumab on top of intensive statin therapy reduced major adverse cardiovascular events and all-cause mortality significantly more than placebo plus intensive statin therapy in patients with a recent acute coronary syndrome and an elevated on-statin LDL cholesterol level. 

Bruce Jancin/Frontline Medical News

ODYSSEY Outcomes was a double-blind trial in which 18,924 patients at 1,315 sites in 57 countries were randomized to alirocumab (Praluent) or placebo plus background high-intensity statin therapy starting a median of 2.5 months after an acute coronary syndrome. All participants had to have a baseline LDL cholesterol level of 70 mg/dL or higher despite intensive statin therapy. Alirocumab was titrated to maintain a target LDL of 25-50 mg/dL. An LDL of 15-25 mg/dL was deemed acceptable, but if the level dropped below 15 mg/dL on two consecutive measurements the patient was blindly switched to placebo, as occurred in 7.7% of the alirocumab group. 

The primary study endpoint was a composite outcome comprised of CHD (coronary heart disease) death, nonfatal MI, ischemic stroke, or unstable angina requiring hospitalization. During a median 2.8 years of follow-up, this outcome occurred in 9.5% of the overall population randomized to alirocumab and 11.1% of those on placebo, for a statistically significant and clinically meaningful 15% reduction in relative risk. The CHD death rates in the two study arms were similar; however, the other three components of the primary endpoint occurred significantly less often in the alirocumab group: The risk of nonfatal MI was 14% less (6.6% vs. 7.6%), ischemic stroke was 27% less (1.2 vs. 1.6%), and unstable angina was 39% less (0.4% vs. 0.6%).

All-cause mortality occurred in 3.5% of patients receiving alirocumab and 4.1% on placebo, once again for a statistically significant 15% reduction in risk. This was a major achievement, since even statins haven’t shown a mortality benefit in the post-ACS setting, observed Dr. Steg, cochair of the study. 

The greatest benefits were seen in the 5,629 participants with a baseline LDL of 100 mg/dL or more on high-intensity statin therapy. In this large subgroup at highest baseline risk, alirocumab resulted in an absolute 3.4% risk reduction and a 24% reduction in relative risk of MACE. All-cause mortality decreased by an absolute 1.7%, translating to a 29% relative risk reduction. The number-needed-to-treat (NNT) for the duration of the study in order to prevent one additional MACE event in this group was 29, with an NNT to prevent one additional death of 60, added Dr. Steg, professor of cardiology at the University of Paris and chief of cardiology at Bichat Hospital. 

“The risk/benefit for alirocumab is extraordinarily favorable. There was almost no risk over the course of the trial. There was no increase in neurocognitive disorders, new-onset or worsening diabetes, cataracts, or hemorrhagic stroke,” the cardiologist said. 
Indeed, the sole adverse event that occurred more frequently in the alirocumab group was mild local injection site reactions, which occurred in 3.8% of the alirocumab group and 2.1% of controls. 

There was a tendency for LDL to creep upward in both the alirocumab and placebo arms over the course of follow-up. Dr. Steg attributed this to down-titration or cessation of alirocumab as per protocol along with the inability of a substantial proportion of patients to tolerate intensive statin therapy. Most study participants had never been on a statin until their ACS. 

A year ago at ACC 2017, other investigators presented the results of FOURIER, a large clinical outcomes trial of evolocumab (Repatha), another PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitor. FOURIER also showed a 15% relative risk reduction in major adverse cardiovascular events, but unlike in ODYSSEY Outcomes, there was no significant impact upon mortality. Dr. Steg attributed this to several key differences between the two trials.

The post-ACS population of ODYSSEY Outcomes was on average higher-risk than FOURIER participants, who had stable atherosclerotic cardiovascular disease. The background statin therapy was more intensive in ODYSSEY, and the average follow-up was close to 8 months longer, too. 

Bruce Jancin/Frontline Medical News

The study population is representative of an enormous number of patients seen in clinical practice, added Dr. Fuster, professor of medicine and physician-in-chief at Mount Sinai Hospital in New York. He estimated that one-third of patients who experience ACS can’t subsequently get their LDL down to the 70 mg/dL range on statin therapy, generally because of drug intolerance. 
He voiced a concern: “Up until now, the feasibility and affordability of using this type of drug has been extremely difficult. I hope this particular study is a trigger – a catalyzer – for making this drug much more available to people who need it.” 

The study met with an enthusiastic audience reception. Prior to presentation of the results at the meeting’s opening session, 79% of the audience of more than 4,000 in the main arena indicated they either don’t prescribe PCSK9 inhibitors or do so only a handful of times per year.

Immediately after seeing the data, 62% of the audience said their practice will change as a result of the study findings. 

ODYSSEY Outcomes was funded by Sanofi and Regeneron Pharmaceuticals. Dr. Steg reported serving as a consultant to and receiving research grants from those pharmaceutical companies and numerous others. 

bjancin@frontlinemedcom.com 
SOURCE: Steg GP. 

ORLANDO – In what was hailed as a major advance in preventive cardiology, the ODYSSEY Outcomes trial has shown that adding the PCSK9 inhibitor alirocumab on top of intensive statin therapy reduced major adverse cardiovascular events and all-cause mortality significantly more than placebo plus intensive statin therapy in patients with a recent acute coronary syndrome and an elevated on-statin LDL cholesterol level. 

Bruce Jancin/Frontline Medical News

ODYSSEY Outcomes was a double-blind trial in which 18,924 patients at 1,315 sites in 57 countries were randomized to alirocumab (Praluent) or placebo plus background high-intensity statin therapy starting a median of 2.5 months after an acute coronary syndrome. All participants had to have a baseline LDL cholesterol level of 70 mg/dL or higher despite intensive statin therapy. Alirocumab was titrated to maintain a target LDL of 25-50 mg/dL. An LDL of 15-25 mg/dL was deemed acceptable, but if the level dropped below 15 mg/dL on two consecutive measurements the patient was blindly switched to placebo, as occurred in 7.7% of the alirocumab group. 

The primary study endpoint was a composite outcome comprised of CHD (coronary heart disease) death, nonfatal MI, ischemic stroke, or unstable angina requiring hospitalization. During a median 2.8 years of follow-up, this outcome occurred in 9.5% of the overall population randomized to alirocumab and 11.1% of those on placebo, for a statistically significant and clinically meaningful 15% reduction in relative risk. The CHD death rates in the two study arms were similar; however, the other three components of the primary endpoint occurred significantly less often in the alirocumab group: The risk of nonfatal MI was 14% less (6.6% vs. 7.6%), ischemic stroke was 27% less (1.2 vs. 1.6%), and unstable angina was 39% less (0.4% vs. 0.6%).

All-cause mortality occurred in 3.5% of patients receiving alirocumab and 4.1% on placebo, once again for a statistically significant 15% reduction in risk. This was a major achievement, since even statins haven’t shown a mortality benefit in the post-ACS setting, observed Dr. Steg, cochair of the study. 

The greatest benefits were seen in the 5,629 participants with a baseline LDL of 100 mg/dL or more on high-intensity statin therapy. In this large subgroup at highest baseline risk, alirocumab resulted in an absolute 3.4% risk reduction and a 24% reduction in relative risk of MACE. All-cause mortality decreased by an absolute 1.7%, translating to a 29% relative risk reduction. The number-needed-to-treat (NNT) for the duration of the study in order to prevent one additional MACE event in this group was 29, with an NNT to prevent one additional death of 60, added Dr. Steg, professor of cardiology at the University of Paris and chief of cardiology at Bichat Hospital. 

“The risk/benefit for alirocumab is extraordinarily favorable. There was almost no risk over the course of the trial. There was no increase in neurocognitive disorders, new-onset or worsening diabetes, cataracts, or hemorrhagic stroke,” the cardiologist said. 
Indeed, the sole adverse event that occurred more frequently in the alirocumab group was mild local injection site reactions, which occurred in 3.8% of the alirocumab group and 2.1% of controls. 

There was a tendency for LDL to creep upward in both the alirocumab and placebo arms over the course of follow-up. Dr. Steg attributed this to down-titration or cessation of alirocumab as per protocol along with the inability of a substantial proportion of patients to tolerate intensive statin therapy. Most study participants had never been on a statin until their ACS. 

A year ago at ACC 2017, other investigators presented the results of FOURIER, a large clinical outcomes trial of evolocumab (Repatha), another PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitor. FOURIER also showed a 15% relative risk reduction in major adverse cardiovascular events, but unlike in ODYSSEY Outcomes, there was no significant impact upon mortality. Dr. Steg attributed this to several key differences between the two trials.

The post-ACS population of ODYSSEY Outcomes was on average higher-risk than FOURIER participants, who had stable atherosclerotic cardiovascular disease. The background statin therapy was more intensive in ODYSSEY, and the average follow-up was close to 8 months longer, too. 

Bruce Jancin/Frontline Medical News

The study population is representative of an enormous number of patients seen in clinical practice, added Dr. Fuster, professor of medicine and physician-in-chief at Mount Sinai Hospital in New York. He estimated that one-third of patients who experience ACS can’t subsequently get their LDL down to the 70 mg/dL range on statin therapy, generally because of drug intolerance. 
He voiced a concern: “Up until now, the feasibility and affordability of using this type of drug has been extremely difficult. I hope this particular study is a trigger – a catalyzer – for making this drug much more available to people who need it.” 

The study met with an enthusiastic audience reception. Prior to presentation of the results at the meeting’s opening session, 79% of the audience of more than 4,000 in the main arena indicated they either don’t prescribe PCSK9 inhibitors or do so only a handful of times per year.

Immediately after seeing the data, 62% of the audience said their practice will change as a result of the study findings. 

ODYSSEY Outcomes was funded by Sanofi and Regeneron Pharmaceuticals. Dr. Steg reported serving as a consultant to and receiving research grants from those pharmaceutical companies and numerous others. 

bjancin@frontlinemedcom.com 
SOURCE: Steg GP. 

ORLANDO – The ODYSSEY Outcomes trial proves the point that LDL-cholesterol reduction with PCSK9 inhibitors can reduce not only cardiovascular events, but all-cause mortality, Prakash Deedwania, MD, said in an interview at the annual meeting of the American College of Cardiology.

That mortality reduction builds on the FOURIER trial results, which showed last year that evolocumab significantly reduced cardiovascular events in patients with stable atherosclerotic cardiovascular disease who were still at residual risk based on elevated LDL cholesterol levels said Dr. Deedwania, professor of medicine at the University of California, San Francisco, in Fresno, who was not involved with ODYSSEY Outcomes.

However, one finding about mortality in ODYSSEY Outcomes was disappointing: LDL levels increase slightly over time in both the treatment and placebo groups.

Source: Deedwania P ACC 18.




 

ORLANDO – The ODYSSEY Outcomes trial proves the point that LDL-cholesterol reduction with PCSK9 inhibitors can reduce not only cardiovascular events, but all-cause mortality, Prakash Deedwania, MD, said in an interview at the annual meeting of the American College of Cardiology.

That mortality reduction builds on the FOURIER trial results, which showed last year that evolocumab significantly reduced cardiovascular events in patients with stable atherosclerotic cardiovascular disease who were still at residual risk based on elevated LDL cholesterol levels said Dr. Deedwania, professor of medicine at the University of California, San Francisco, in Fresno, who was not involved with ODYSSEY Outcomes.

However, one finding about mortality in ODYSSEY Outcomes was disappointing: LDL levels increase slightly over time in both the treatment and placebo groups.

Source: Deedwania P ACC 18.




 

ORLANDO – The ODYSSEY Outcomes trial proves the point that LDL-cholesterol reduction with PCSK9 inhibitors can reduce not only cardiovascular events, but all-cause mortality, Prakash Deedwania, MD, said in an interview at the annual meeting of the American College of Cardiology.

That mortality reduction builds on the FOURIER trial results, which showed last year that evolocumab significantly reduced cardiovascular events in patients with stable atherosclerotic cardiovascular disease who were still at residual risk based on elevated LDL cholesterol levels said Dr. Deedwania, professor of medicine at the University of California, San Francisco, in Fresno, who was not involved with ODYSSEY Outcomes.

However, one finding about mortality in ODYSSEY Outcomes was disappointing: LDL levels increase slightly over time in both the treatment and placebo groups.

Source: Deedwania P ACC 18.