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VIDEO: Evolocumab caused no cognitive issues in FOURIER substudy
WASHINGTON – Don’t give the cognitive effects of evolocumab a second thought, results from a preplanned substudy of the landmark FOURIER study that assessed the impact of this PCSK9 inhibitor on memory or other measures of cognition in a random subgroup of 1,973 patients enrolled in the main study suggest.
Based on these results “I wouldn’t be concerned about adverse cognitive effects” in patients treated with evolocumab (Repatha) or, for the time being, any other PCSK9 inhibitor, said Robert P. Giugliano, MD, in a video interview at the annual meeting of the American College of Cardiology”
Concerns about the cognitive effects of the drugs in this class of lipid-lowering drugs have lingered following suggestions of a possible problem that arose during earlier, much smaller studies of these agents as well as similar concerns that arose about statins that have been perpetuated through misleading posts on the Internet.
The battery of memory and cognition assessments used in EBBINGHAUS, the FOURIER substudy, should lay concerns about brain effects of evolocumab to rest, at least within the context of the median 26 months of treatment that patients in FOURIER received, said Dr. Giugliano, a cardiologist at Brigham and Women’s Hospital in Boston and lead investigator of the EBBINGHAUS substudy. Further analysis also showed that, even among patients who achieved LDL cholesterol levels of less than 25 mg/dL, treatment with evolocumab appeared to cause no deterioration of the measured mental functions.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
[email protected]
On Twitter @mitchelzoler
WASHINGTON – Don’t give the cognitive effects of evolocumab a second thought, results from a preplanned substudy of the landmark FOURIER study that assessed the impact of this PCSK9 inhibitor on memory or other measures of cognition in a random subgroup of 1,973 patients enrolled in the main study suggest.
Based on these results “I wouldn’t be concerned about adverse cognitive effects” in patients treated with evolocumab (Repatha) or, for the time being, any other PCSK9 inhibitor, said Robert P. Giugliano, MD, in a video interview at the annual meeting of the American College of Cardiology”
Concerns about the cognitive effects of the drugs in this class of lipid-lowering drugs have lingered following suggestions of a possible problem that arose during earlier, much smaller studies of these agents as well as similar concerns that arose about statins that have been perpetuated through misleading posts on the Internet.
The battery of memory and cognition assessments used in EBBINGHAUS, the FOURIER substudy, should lay concerns about brain effects of evolocumab to rest, at least within the context of the median 26 months of treatment that patients in FOURIER received, said Dr. Giugliano, a cardiologist at Brigham and Women’s Hospital in Boston and lead investigator of the EBBINGHAUS substudy. Further analysis also showed that, even among patients who achieved LDL cholesterol levels of less than 25 mg/dL, treatment with evolocumab appeared to cause no deterioration of the measured mental functions.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
[email protected]
On Twitter @mitchelzoler
WASHINGTON – Don’t give the cognitive effects of evolocumab a second thought, results from a preplanned substudy of the landmark FOURIER study that assessed the impact of this PCSK9 inhibitor on memory or other measures of cognition in a random subgroup of 1,973 patients enrolled in the main study suggest.
Based on these results “I wouldn’t be concerned about adverse cognitive effects” in patients treated with evolocumab (Repatha) or, for the time being, any other PCSK9 inhibitor, said Robert P. Giugliano, MD, in a video interview at the annual meeting of the American College of Cardiology”
Concerns about the cognitive effects of the drugs in this class of lipid-lowering drugs have lingered following suggestions of a possible problem that arose during earlier, much smaller studies of these agents as well as similar concerns that arose about statins that have been perpetuated through misleading posts on the Internet.
The battery of memory and cognition assessments used in EBBINGHAUS, the FOURIER substudy, should lay concerns about brain effects of evolocumab to rest, at least within the context of the median 26 months of treatment that patients in FOURIER received, said Dr. Giugliano, a cardiologist at Brigham and Women’s Hospital in Boston and lead investigator of the EBBINGHAUS substudy. Further analysis also showed that, even among patients who achieved LDL cholesterol levels of less than 25 mg/dL, treatment with evolocumab appeared to cause no deterioration of the measured mental functions.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
[email protected]
On Twitter @mitchelzoler
AT ACC 2017
Evolocumab strikes gold in FOURIER trial
WASHINGTON – The PCSK9 inhibitor evolocumab reduced the incidence of the composite endpoint of cardiovascular death, MI, or stroke by an additional 20% in patients with established cardiovascular disease who were already on background maximum-tolerated statin therapy in the landmark FOURIER trial, Marc S. Sabatine, MD, reported at the annual meeting of the American College of Cardiology.
FOURIER (Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk) was eagerly anticipated as the first dedicated cardiovascular outcomes trial to report results for a proprotein convertase subtilisin/kexin type 9 inhibitor, the novel drug class that achieves previously unattainable LDL lowering.
FOURIER randomized 27,564 patients with preexisting high-risk cardiovascular disease in 49 countries to double-blind therapy with subcutaneous evolocumab (Repatha) at either 140 mg every 2 weeks or 420 mg once monthly or to placebo injections. Participants had a baseline LDL-cholesterol level of 70 mg/dL or above while on statin therapy, which continued throughout the study. Sixty-nine percent of subjects were on high-intensity statin therapy, and the rest were on a moderate-intensity statin.
The median LDL level plunged from 92 mg/dL at baseline to 30 mg/dL in the evolocumab group, a 59% reduction. Moreover, one-quarter of patients on evolocumab achieved an LDL below 20 mg/dL. And this effect remained durable over the median 26 months of study follow-up.
“The LDL reduction achieved with evolocumab was rock steady over time,” observed Dr. Sabatine, professor of medicine at Harvard Medical School, Boston, and chair of the Thrombolysis in Myocardial Infarction Study Group.
The primary study endpoint – a composite of cardiovascular death, MI, stroke, hospitalization for unstable angina, or coronary revascularization – occurred in 11.3% of controls and 9.8% of the evolocumab group, for a significant 15% relative risk reduction. But Dr. Sabatine drew attention to the prespecified and fully powered secondary endpoint of cardiovascular death, MI, or stroke, which he considers more clinically relevant: 7.4% in controls, compared with 5.9% in the evolocumab group, for a 20% reduction in risk.
The cardiovascular benefits of greater lipid lowering grew over time. The evolocumab group’s relative risk reduction in the secondary composite endpoint was 16% in the first 12 months of follow-up and 25% beyond 12 months.
Even more impressively, the relative risk reduction in the stripped-down secondary endpoint of fatal or nonfatal MI or stroke was 19% in the first 12 months and 33%, compared with placebo, beyond 12 months.
The benefit in terms of cardiovascular risk reduction was consistent across baseline LDL subgroups, including those in the lowest baseline quartile, whose average baseline LDL was 74 mg/dL. Thus, the former LDL goal of a target below 70 mg/dL as representing maximum benefit has flown out the window.
“Even lower LDL appears to be even better, now down in this trial to 22 mg/dL,” the cardiologist declared.
There was no significant difference between the two study arms in the cardiovascular mortality rate, although Dr. Sabatine didn’t consider that surprising.
“Over the past decade, none of the trials of more intensive LDL lowering when compared with patients on moderate-intensity LDL-lowering therapy showed a significant reduction in cardiovascular mortality, which thankfully is now less common after acute MI and acute stroke than it had been in the past,” he said.
The number needed to treat (NNT) in order to prevent one additional cardiovascular death, MI, or stroke, based upon the current 3-year follow-up data, is roughly 50, according to Dr. Sabatine. Projecting out to 5 years, based upon the close fit between FOURIER and the data from the Cholesterol Treatment Trialists Collaboration, the NNT at 5 years for evolocumab is about 30, although the true NNT may actually prove to be smaller than that, given the steadily increasing benefit seen through 3 years. The projected 5-year NNT for the composite of coronary revascularization, cardiovascular death, MI, or stroke drops to about 20, he added.
The treatment was safe and well tolerated. The rate of study discontinuation attributable to treatment-related adverse events was low, at about 1.5% in both treatment arms. The rates of neurocognitive adverse events, new-onset diabetes, cataracts, and muscle-related complaints didn’t differ between the evolocumab and placebo groups, either. Of note, no one developed neutralizing antibodies to evolocumab. Long-term follow-up will continue in roughly 6,000 FOURIER participants.
Discussant Pamela B. Morris, MD, said FOURIER contains an important secondary message that mustn’t get lost in the enthusiasm for a safe and effective new drug.
“I’m very struck by the high event rate in this population, even with LDL levels down to 30 mg/dL. I think what that says is that although LDL cholesterol is etiologic and incredibly important, there were multiple other risk factors in this population, and given a 4.2% event rate per year despite achieving a very low LDL, we can’t take our foot off the gas in terms of other risk factors,” said Dr. Morris of the Medical University of South Carolina, Charleston.
Discussant Sidney C. Smith Jr., MD, a member of the 2013 ACC/AHA cholesterol treatment guidelines committee, which did away with LDL lowering to a target level in favor of a risk-based approach which embraced percent reduction in LDL as a therapeutic goal, asked Dr. Sabatine if it’s time for the committee to revisit and perhaps restore the concept of shooting for an LDL target range.
“We labored with that in the 2013 guidelines, as to whether there’s some optimal range for LDL or one can look at percent reduction as an indicator,” noted Dr. Smith, professor of medicine at the University of North Carolina in Chapel Hill.
Dr. Sabatine replied, “Dr. [Eugene] Braunwald has made the analogy that if this was smoking, we wouldn’t want people to just reduce their amount of smoking by 50%, we’d want them to reduce it to zero cigarettes.”
The investigator added, “My own feeling is that the benefit is more closely related to the absolute reduction than the percent reduction in LDL, and like any other risk factor, you want to get it down as low as you can go.”
In a later video interview, Dr. Smith said that the FOURIER data make a strong case – at least in these first years of what will be much-longer-term drug therapy – that a target LDL in the range of 25-35 mg/dL may be optimal in a very-high-risk patient population.
Dr. Sabatine reported receiving grant support and consultant fees from Amgen, which funded the FOURIER trial.
Simultaneous with his presentation at the ACC meeting, the FOURIER results were published online at NEJM.org (doi: 10.1056/NEJMoa1615664).
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
WASHINGTON – The PCSK9 inhibitor evolocumab reduced the incidence of the composite endpoint of cardiovascular death, MI, or stroke by an additional 20% in patients with established cardiovascular disease who were already on background maximum-tolerated statin therapy in the landmark FOURIER trial, Marc S. Sabatine, MD, reported at the annual meeting of the American College of Cardiology.
FOURIER (Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk) was eagerly anticipated as the first dedicated cardiovascular outcomes trial to report results for a proprotein convertase subtilisin/kexin type 9 inhibitor, the novel drug class that achieves previously unattainable LDL lowering.
FOURIER randomized 27,564 patients with preexisting high-risk cardiovascular disease in 49 countries to double-blind therapy with subcutaneous evolocumab (Repatha) at either 140 mg every 2 weeks or 420 mg once monthly or to placebo injections. Participants had a baseline LDL-cholesterol level of 70 mg/dL or above while on statin therapy, which continued throughout the study. Sixty-nine percent of subjects were on high-intensity statin therapy, and the rest were on a moderate-intensity statin.
The median LDL level plunged from 92 mg/dL at baseline to 30 mg/dL in the evolocumab group, a 59% reduction. Moreover, one-quarter of patients on evolocumab achieved an LDL below 20 mg/dL. And this effect remained durable over the median 26 months of study follow-up.
“The LDL reduction achieved with evolocumab was rock steady over time,” observed Dr. Sabatine, professor of medicine at Harvard Medical School, Boston, and chair of the Thrombolysis in Myocardial Infarction Study Group.
The primary study endpoint – a composite of cardiovascular death, MI, stroke, hospitalization for unstable angina, or coronary revascularization – occurred in 11.3% of controls and 9.8% of the evolocumab group, for a significant 15% relative risk reduction. But Dr. Sabatine drew attention to the prespecified and fully powered secondary endpoint of cardiovascular death, MI, or stroke, which he considers more clinically relevant: 7.4% in controls, compared with 5.9% in the evolocumab group, for a 20% reduction in risk.
The cardiovascular benefits of greater lipid lowering grew over time. The evolocumab group’s relative risk reduction in the secondary composite endpoint was 16% in the first 12 months of follow-up and 25% beyond 12 months.
Even more impressively, the relative risk reduction in the stripped-down secondary endpoint of fatal or nonfatal MI or stroke was 19% in the first 12 months and 33%, compared with placebo, beyond 12 months.
The benefit in terms of cardiovascular risk reduction was consistent across baseline LDL subgroups, including those in the lowest baseline quartile, whose average baseline LDL was 74 mg/dL. Thus, the former LDL goal of a target below 70 mg/dL as representing maximum benefit has flown out the window.
“Even lower LDL appears to be even better, now down in this trial to 22 mg/dL,” the cardiologist declared.
There was no significant difference between the two study arms in the cardiovascular mortality rate, although Dr. Sabatine didn’t consider that surprising.
“Over the past decade, none of the trials of more intensive LDL lowering when compared with patients on moderate-intensity LDL-lowering therapy showed a significant reduction in cardiovascular mortality, which thankfully is now less common after acute MI and acute stroke than it had been in the past,” he said.
The number needed to treat (NNT) in order to prevent one additional cardiovascular death, MI, or stroke, based upon the current 3-year follow-up data, is roughly 50, according to Dr. Sabatine. Projecting out to 5 years, based upon the close fit between FOURIER and the data from the Cholesterol Treatment Trialists Collaboration, the NNT at 5 years for evolocumab is about 30, although the true NNT may actually prove to be smaller than that, given the steadily increasing benefit seen through 3 years. The projected 5-year NNT for the composite of coronary revascularization, cardiovascular death, MI, or stroke drops to about 20, he added.
The treatment was safe and well tolerated. The rate of study discontinuation attributable to treatment-related adverse events was low, at about 1.5% in both treatment arms. The rates of neurocognitive adverse events, new-onset diabetes, cataracts, and muscle-related complaints didn’t differ between the evolocumab and placebo groups, either. Of note, no one developed neutralizing antibodies to evolocumab. Long-term follow-up will continue in roughly 6,000 FOURIER participants.
Discussant Pamela B. Morris, MD, said FOURIER contains an important secondary message that mustn’t get lost in the enthusiasm for a safe and effective new drug.
“I’m very struck by the high event rate in this population, even with LDL levels down to 30 mg/dL. I think what that says is that although LDL cholesterol is etiologic and incredibly important, there were multiple other risk factors in this population, and given a 4.2% event rate per year despite achieving a very low LDL, we can’t take our foot off the gas in terms of other risk factors,” said Dr. Morris of the Medical University of South Carolina, Charleston.
Discussant Sidney C. Smith Jr., MD, a member of the 2013 ACC/AHA cholesterol treatment guidelines committee, which did away with LDL lowering to a target level in favor of a risk-based approach which embraced percent reduction in LDL as a therapeutic goal, asked Dr. Sabatine if it’s time for the committee to revisit and perhaps restore the concept of shooting for an LDL target range.
“We labored with that in the 2013 guidelines, as to whether there’s some optimal range for LDL or one can look at percent reduction as an indicator,” noted Dr. Smith, professor of medicine at the University of North Carolina in Chapel Hill.
Dr. Sabatine replied, “Dr. [Eugene] Braunwald has made the analogy that if this was smoking, we wouldn’t want people to just reduce their amount of smoking by 50%, we’d want them to reduce it to zero cigarettes.”
The investigator added, “My own feeling is that the benefit is more closely related to the absolute reduction than the percent reduction in LDL, and like any other risk factor, you want to get it down as low as you can go.”
In a later video interview, Dr. Smith said that the FOURIER data make a strong case – at least in these first years of what will be much-longer-term drug therapy – that a target LDL in the range of 25-35 mg/dL may be optimal in a very-high-risk patient population.
Dr. Sabatine reported receiving grant support and consultant fees from Amgen, which funded the FOURIER trial.
Simultaneous with his presentation at the ACC meeting, the FOURIER results were published online at NEJM.org (doi: 10.1056/NEJMoa1615664).
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
WASHINGTON – The PCSK9 inhibitor evolocumab reduced the incidence of the composite endpoint of cardiovascular death, MI, or stroke by an additional 20% in patients with established cardiovascular disease who were already on background maximum-tolerated statin therapy in the landmark FOURIER trial, Marc S. Sabatine, MD, reported at the annual meeting of the American College of Cardiology.
FOURIER (Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk) was eagerly anticipated as the first dedicated cardiovascular outcomes trial to report results for a proprotein convertase subtilisin/kexin type 9 inhibitor, the novel drug class that achieves previously unattainable LDL lowering.
FOURIER randomized 27,564 patients with preexisting high-risk cardiovascular disease in 49 countries to double-blind therapy with subcutaneous evolocumab (Repatha) at either 140 mg every 2 weeks or 420 mg once monthly or to placebo injections. Participants had a baseline LDL-cholesterol level of 70 mg/dL or above while on statin therapy, which continued throughout the study. Sixty-nine percent of subjects were on high-intensity statin therapy, and the rest were on a moderate-intensity statin.
The median LDL level plunged from 92 mg/dL at baseline to 30 mg/dL in the evolocumab group, a 59% reduction. Moreover, one-quarter of patients on evolocumab achieved an LDL below 20 mg/dL. And this effect remained durable over the median 26 months of study follow-up.
“The LDL reduction achieved with evolocumab was rock steady over time,” observed Dr. Sabatine, professor of medicine at Harvard Medical School, Boston, and chair of the Thrombolysis in Myocardial Infarction Study Group.
The primary study endpoint – a composite of cardiovascular death, MI, stroke, hospitalization for unstable angina, or coronary revascularization – occurred in 11.3% of controls and 9.8% of the evolocumab group, for a significant 15% relative risk reduction. But Dr. Sabatine drew attention to the prespecified and fully powered secondary endpoint of cardiovascular death, MI, or stroke, which he considers more clinically relevant: 7.4% in controls, compared with 5.9% in the evolocumab group, for a 20% reduction in risk.
The cardiovascular benefits of greater lipid lowering grew over time. The evolocumab group’s relative risk reduction in the secondary composite endpoint was 16% in the first 12 months of follow-up and 25% beyond 12 months.
Even more impressively, the relative risk reduction in the stripped-down secondary endpoint of fatal or nonfatal MI or stroke was 19% in the first 12 months and 33%, compared with placebo, beyond 12 months.
The benefit in terms of cardiovascular risk reduction was consistent across baseline LDL subgroups, including those in the lowest baseline quartile, whose average baseline LDL was 74 mg/dL. Thus, the former LDL goal of a target below 70 mg/dL as representing maximum benefit has flown out the window.
“Even lower LDL appears to be even better, now down in this trial to 22 mg/dL,” the cardiologist declared.
There was no significant difference between the two study arms in the cardiovascular mortality rate, although Dr. Sabatine didn’t consider that surprising.
“Over the past decade, none of the trials of more intensive LDL lowering when compared with patients on moderate-intensity LDL-lowering therapy showed a significant reduction in cardiovascular mortality, which thankfully is now less common after acute MI and acute stroke than it had been in the past,” he said.
The number needed to treat (NNT) in order to prevent one additional cardiovascular death, MI, or stroke, based upon the current 3-year follow-up data, is roughly 50, according to Dr. Sabatine. Projecting out to 5 years, based upon the close fit between FOURIER and the data from the Cholesterol Treatment Trialists Collaboration, the NNT at 5 years for evolocumab is about 30, although the true NNT may actually prove to be smaller than that, given the steadily increasing benefit seen through 3 years. The projected 5-year NNT for the composite of coronary revascularization, cardiovascular death, MI, or stroke drops to about 20, he added.
The treatment was safe and well tolerated. The rate of study discontinuation attributable to treatment-related adverse events was low, at about 1.5% in both treatment arms. The rates of neurocognitive adverse events, new-onset diabetes, cataracts, and muscle-related complaints didn’t differ between the evolocumab and placebo groups, either. Of note, no one developed neutralizing antibodies to evolocumab. Long-term follow-up will continue in roughly 6,000 FOURIER participants.
Discussant Pamela B. Morris, MD, said FOURIER contains an important secondary message that mustn’t get lost in the enthusiasm for a safe and effective new drug.
“I’m very struck by the high event rate in this population, even with LDL levels down to 30 mg/dL. I think what that says is that although LDL cholesterol is etiologic and incredibly important, there were multiple other risk factors in this population, and given a 4.2% event rate per year despite achieving a very low LDL, we can’t take our foot off the gas in terms of other risk factors,” said Dr. Morris of the Medical University of South Carolina, Charleston.
Discussant Sidney C. Smith Jr., MD, a member of the 2013 ACC/AHA cholesterol treatment guidelines committee, which did away with LDL lowering to a target level in favor of a risk-based approach which embraced percent reduction in LDL as a therapeutic goal, asked Dr. Sabatine if it’s time for the committee to revisit and perhaps restore the concept of shooting for an LDL target range.
“We labored with that in the 2013 guidelines, as to whether there’s some optimal range for LDL or one can look at percent reduction as an indicator,” noted Dr. Smith, professor of medicine at the University of North Carolina in Chapel Hill.
Dr. Sabatine replied, “Dr. [Eugene] Braunwald has made the analogy that if this was smoking, we wouldn’t want people to just reduce their amount of smoking by 50%, we’d want them to reduce it to zero cigarettes.”
The investigator added, “My own feeling is that the benefit is more closely related to the absolute reduction than the percent reduction in LDL, and like any other risk factor, you want to get it down as low as you can go.”
In a later video interview, Dr. Smith said that the FOURIER data make a strong case – at least in these first years of what will be much-longer-term drug therapy – that a target LDL in the range of 25-35 mg/dL may be optimal in a very-high-risk patient population.
Dr. Sabatine reported receiving grant support and consultant fees from Amgen, which funded the FOURIER trial.
Simultaneous with his presentation at the ACC meeting, the FOURIER results were published online at NEJM.org (doi: 10.1056/NEJMoa1615664).
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
Key clinical point:
Major finding: The projected NNT with evolocumab for 5 years in order to prevent one additional cardiovascular death, MI, or stroke is roughly 30 patients.
Data source: The FOURIER trial was a randomized, double-blind, placebo-controlled trial including more than 27,000 patients with high-risk cardiovascular disease on background statin therapy.
Disclosures: The presenter reported receiving grant support and consultant fees from Amgen, which funded the study.
Calcium scores may assist cardiac screening in African Americans
A new study suggests calcium scores may help physicians as they navigate a wide cardiac screening guideline gap over recommendations about statin therapy in African Americans.
In a study sample of Mississippi residents, researchers found that the 2016 U.S. Preventive Services Task Force guidelines would reject statins for a quarter of the African Americans who’d be deemed statin eligible by the 2013 American College of Cardiology/American Heart Association (ACC/AHA) recommendations.
“ACC/AHA guidelines are more sensitive, but may lead to overtreatment of those who may not be at increased risk of cardiovascular disease,” said study coauthor Aferdita Spahillari, MD, a cardiology fellow at Tufts Medical Center and Beth Israel Deaconess Medical Center, Boston. In contrast, the task force guidelines “are more specific, yet they may miss individuals at higher risk who should be treated with statins,” she said.
Regardless of which screening guidelines are used, Dr. Spahillari said, “calcium scoring may aid decision making in those cases where guideline recommendations may be divergent.”
The study was presented at the annual meeting of the American College of Cardiology and published simultaneously in the JAMA Cardiology (doi: 10.1001/jamacardio.2017.0944).
The researchers sought to answer these questions: How do the ACC/AHA and task force guidelines perform at identifying at-risk African Americans? And can calcium scores help refine decisions regarding statins? According to Dr. Spahillari, the latter issue has been studied in whites but not large African American populations.
Insight could help physicians better provide preventive treatment to African Americans, who face a higher risk of cardiac problems compared with whites. In addition, “studies have shown that racial disparities exist in prescription of cardioprotective medications,” Dr. Spahillari said, “and African Americans are prescribed statins less frequently than whites.”
For the new study, researchers tracked 2,812 African American individuals aged 40-75 years (mean age 55 [SD 9.4], 65.3% female, mean body mass index 31.6 kg/m2 [SD 7.0]) in the Jackson, Miss., area. They were examined in 2000-2004, 2005-2008, and 2009-2013 and included if they didn’t show signs of prevalent subclinical and clinical atherosclerotic cardiovascular disease and weren’t on statins at baseline.
If the task force guidelines regarding 10-year risk had been in existence, 1,072 (38.1%) of the participants would have been deemed eligible for treatment. A higher number – 1,404 (49.9%) – would have been eligible under ACC/AHA guidelines (risk difference, 11.8%; 95% CI, 10.5-13.1; P less than .001).
The two sets of guidelines diverged on the eligibility of 13.8% of the total subjects: 361 (12.8%) were deemed eligible for statins by the ACC/AHA guidelines alone. (They account for 25.7% of all the statin-eligible subjects under the ACC/AHA guidelines.)
In contrast, the task force guidelines alone deemed 29 (1%) to be eligible.
Those deemed eligible for statins under both guidelines had a cardiovascular event rate of 9.6 per 1,000 patient-years (95% CI, 7.8-11.8, P = .003) over a median 10-year follow-up. The event rate for those only statin-eligible under the ACC/AHA guidelines had an event rate of 4.1 events per 1,000 patient-years (95% CI, 2.4-6.9; P = .003), which Dr. Spahillari calls “a low to intermediate rate suggesting a decreased sensitivity of the task force recommendations in identifying participants at risk of atherosclerotic cardiovascular disease.”
And what about CAC levels? Task force guidelines identified 404 of 732 (55.2%) African Americans with coronary calcium; ACC/AHA guidelines identified 507 (69.3%).
“Participants eligible for statins under the ACC/AHA guidelines who had CAC were at higher risk than those without CAC,” Dr. Spahillari said. Specifically, among those deemed eligible for statins by the ACC/AHA recommendations, the 10-year event rate per 1,000 person-years was 8.1 (95% CI, 5.9-11.1) in those with CAC and 3.1 (95% CI, 1.6-5.9) in those without CAC (P = .02).
The situation was different under the task force guidelines. CAC didn’t significantly affect the risk in those deemed eligible for statins by the task force guidelines, but it did seem to boost risk in those who weren’t statin eligible, she said.
Among those deemed not statin eligible by the task force guidelines, the event rate per 1,000 person-years was 2.8 in those with CAC (95% CI, 1.5-5.4) and 0.8 in those without (95%, CI 0.3-1.7) (P = .03).
How could CAC levels be useful for physicians? “As the role of CAC measurement is evolving, our findings support that measurement of CAC in an African-American population with an intermediate risk score would be clinically useful,” Dr. Spahillari said.
When ACC/AHA guidelines are used, she said, “the absence of CAC may reduce the number of individuals indicated for treatment with statins by ACC/AHA recommendations and temper concerns for overtreatment.”
What if a physician uses the task force guidelines in this population? “The presence of CAC may push a recommendation for statin treatment in individuals who would otherwise not be indicated for statins,” she said.
The National Heart, Lung, and Blood Institute and the National Institute on Minority Health and Health Disparities funded the study. One author reported funding from a National Institutes of Health grant. The others had no disclosures.
A new study suggests calcium scores may help physicians as they navigate a wide cardiac screening guideline gap over recommendations about statin therapy in African Americans.
In a study sample of Mississippi residents, researchers found that the 2016 U.S. Preventive Services Task Force guidelines would reject statins for a quarter of the African Americans who’d be deemed statin eligible by the 2013 American College of Cardiology/American Heart Association (ACC/AHA) recommendations.
“ACC/AHA guidelines are more sensitive, but may lead to overtreatment of those who may not be at increased risk of cardiovascular disease,” said study coauthor Aferdita Spahillari, MD, a cardiology fellow at Tufts Medical Center and Beth Israel Deaconess Medical Center, Boston. In contrast, the task force guidelines “are more specific, yet they may miss individuals at higher risk who should be treated with statins,” she said.
Regardless of which screening guidelines are used, Dr. Spahillari said, “calcium scoring may aid decision making in those cases where guideline recommendations may be divergent.”
The study was presented at the annual meeting of the American College of Cardiology and published simultaneously in the JAMA Cardiology (doi: 10.1001/jamacardio.2017.0944).
The researchers sought to answer these questions: How do the ACC/AHA and task force guidelines perform at identifying at-risk African Americans? And can calcium scores help refine decisions regarding statins? According to Dr. Spahillari, the latter issue has been studied in whites but not large African American populations.
Insight could help physicians better provide preventive treatment to African Americans, who face a higher risk of cardiac problems compared with whites. In addition, “studies have shown that racial disparities exist in prescription of cardioprotective medications,” Dr. Spahillari said, “and African Americans are prescribed statins less frequently than whites.”
For the new study, researchers tracked 2,812 African American individuals aged 40-75 years (mean age 55 [SD 9.4], 65.3% female, mean body mass index 31.6 kg/m2 [SD 7.0]) in the Jackson, Miss., area. They were examined in 2000-2004, 2005-2008, and 2009-2013 and included if they didn’t show signs of prevalent subclinical and clinical atherosclerotic cardiovascular disease and weren’t on statins at baseline.
If the task force guidelines regarding 10-year risk had been in existence, 1,072 (38.1%) of the participants would have been deemed eligible for treatment. A higher number – 1,404 (49.9%) – would have been eligible under ACC/AHA guidelines (risk difference, 11.8%; 95% CI, 10.5-13.1; P less than .001).
The two sets of guidelines diverged on the eligibility of 13.8% of the total subjects: 361 (12.8%) were deemed eligible for statins by the ACC/AHA guidelines alone. (They account for 25.7% of all the statin-eligible subjects under the ACC/AHA guidelines.)
In contrast, the task force guidelines alone deemed 29 (1%) to be eligible.
Those deemed eligible for statins under both guidelines had a cardiovascular event rate of 9.6 per 1,000 patient-years (95% CI, 7.8-11.8, P = .003) over a median 10-year follow-up. The event rate for those only statin-eligible under the ACC/AHA guidelines had an event rate of 4.1 events per 1,000 patient-years (95% CI, 2.4-6.9; P = .003), which Dr. Spahillari calls “a low to intermediate rate suggesting a decreased sensitivity of the task force recommendations in identifying participants at risk of atherosclerotic cardiovascular disease.”
And what about CAC levels? Task force guidelines identified 404 of 732 (55.2%) African Americans with coronary calcium; ACC/AHA guidelines identified 507 (69.3%).
“Participants eligible for statins under the ACC/AHA guidelines who had CAC were at higher risk than those without CAC,” Dr. Spahillari said. Specifically, among those deemed eligible for statins by the ACC/AHA recommendations, the 10-year event rate per 1,000 person-years was 8.1 (95% CI, 5.9-11.1) in those with CAC and 3.1 (95% CI, 1.6-5.9) in those without CAC (P = .02).
The situation was different under the task force guidelines. CAC didn’t significantly affect the risk in those deemed eligible for statins by the task force guidelines, but it did seem to boost risk in those who weren’t statin eligible, she said.
Among those deemed not statin eligible by the task force guidelines, the event rate per 1,000 person-years was 2.8 in those with CAC (95% CI, 1.5-5.4) and 0.8 in those without (95%, CI 0.3-1.7) (P = .03).
How could CAC levels be useful for physicians? “As the role of CAC measurement is evolving, our findings support that measurement of CAC in an African-American population with an intermediate risk score would be clinically useful,” Dr. Spahillari said.
When ACC/AHA guidelines are used, she said, “the absence of CAC may reduce the number of individuals indicated for treatment with statins by ACC/AHA recommendations and temper concerns for overtreatment.”
What if a physician uses the task force guidelines in this population? “The presence of CAC may push a recommendation for statin treatment in individuals who would otherwise not be indicated for statins,” she said.
The National Heart, Lung, and Blood Institute and the National Institute on Minority Health and Health Disparities funded the study. One author reported funding from a National Institutes of Health grant. The others had no disclosures.
A new study suggests calcium scores may help physicians as they navigate a wide cardiac screening guideline gap over recommendations about statin therapy in African Americans.
In a study sample of Mississippi residents, researchers found that the 2016 U.S. Preventive Services Task Force guidelines would reject statins for a quarter of the African Americans who’d be deemed statin eligible by the 2013 American College of Cardiology/American Heart Association (ACC/AHA) recommendations.
“ACC/AHA guidelines are more sensitive, but may lead to overtreatment of those who may not be at increased risk of cardiovascular disease,” said study coauthor Aferdita Spahillari, MD, a cardiology fellow at Tufts Medical Center and Beth Israel Deaconess Medical Center, Boston. In contrast, the task force guidelines “are more specific, yet they may miss individuals at higher risk who should be treated with statins,” she said.
Regardless of which screening guidelines are used, Dr. Spahillari said, “calcium scoring may aid decision making in those cases where guideline recommendations may be divergent.”
The study was presented at the annual meeting of the American College of Cardiology and published simultaneously in the JAMA Cardiology (doi: 10.1001/jamacardio.2017.0944).
The researchers sought to answer these questions: How do the ACC/AHA and task force guidelines perform at identifying at-risk African Americans? And can calcium scores help refine decisions regarding statins? According to Dr. Spahillari, the latter issue has been studied in whites but not large African American populations.
Insight could help physicians better provide preventive treatment to African Americans, who face a higher risk of cardiac problems compared with whites. In addition, “studies have shown that racial disparities exist in prescription of cardioprotective medications,” Dr. Spahillari said, “and African Americans are prescribed statins less frequently than whites.”
For the new study, researchers tracked 2,812 African American individuals aged 40-75 years (mean age 55 [SD 9.4], 65.3% female, mean body mass index 31.6 kg/m2 [SD 7.0]) in the Jackson, Miss., area. They were examined in 2000-2004, 2005-2008, and 2009-2013 and included if they didn’t show signs of prevalent subclinical and clinical atherosclerotic cardiovascular disease and weren’t on statins at baseline.
If the task force guidelines regarding 10-year risk had been in existence, 1,072 (38.1%) of the participants would have been deemed eligible for treatment. A higher number – 1,404 (49.9%) – would have been eligible under ACC/AHA guidelines (risk difference, 11.8%; 95% CI, 10.5-13.1; P less than .001).
The two sets of guidelines diverged on the eligibility of 13.8% of the total subjects: 361 (12.8%) were deemed eligible for statins by the ACC/AHA guidelines alone. (They account for 25.7% of all the statin-eligible subjects under the ACC/AHA guidelines.)
In contrast, the task force guidelines alone deemed 29 (1%) to be eligible.
Those deemed eligible for statins under both guidelines had a cardiovascular event rate of 9.6 per 1,000 patient-years (95% CI, 7.8-11.8, P = .003) over a median 10-year follow-up. The event rate for those only statin-eligible under the ACC/AHA guidelines had an event rate of 4.1 events per 1,000 patient-years (95% CI, 2.4-6.9; P = .003), which Dr. Spahillari calls “a low to intermediate rate suggesting a decreased sensitivity of the task force recommendations in identifying participants at risk of atherosclerotic cardiovascular disease.”
And what about CAC levels? Task force guidelines identified 404 of 732 (55.2%) African Americans with coronary calcium; ACC/AHA guidelines identified 507 (69.3%).
“Participants eligible for statins under the ACC/AHA guidelines who had CAC were at higher risk than those without CAC,” Dr. Spahillari said. Specifically, among those deemed eligible for statins by the ACC/AHA recommendations, the 10-year event rate per 1,000 person-years was 8.1 (95% CI, 5.9-11.1) in those with CAC and 3.1 (95% CI, 1.6-5.9) in those without CAC (P = .02).
The situation was different under the task force guidelines. CAC didn’t significantly affect the risk in those deemed eligible for statins by the task force guidelines, but it did seem to boost risk in those who weren’t statin eligible, she said.
Among those deemed not statin eligible by the task force guidelines, the event rate per 1,000 person-years was 2.8 in those with CAC (95% CI, 1.5-5.4) and 0.8 in those without (95%, CI 0.3-1.7) (P = .03).
How could CAC levels be useful for physicians? “As the role of CAC measurement is evolving, our findings support that measurement of CAC in an African-American population with an intermediate risk score would be clinically useful,” Dr. Spahillari said.
When ACC/AHA guidelines are used, she said, “the absence of CAC may reduce the number of individuals indicated for treatment with statins by ACC/AHA recommendations and temper concerns for overtreatment.”
What if a physician uses the task force guidelines in this population? “The presence of CAC may push a recommendation for statin treatment in individuals who would otherwise not be indicated for statins,” she said.
The National Heart, Lung, and Blood Institute and the National Institute on Minority Health and Health Disparities funded the study. One author reported funding from a National Institutes of Health grant. The others had no disclosures.
FROM ACC 17
Key clinical point: Cardiac screening guidelines diverge on statin-eligible African Americans, but calcium levels can provide treatment insight.
Major finding: U.S. Preventive Services Task Force guidelines did not recommend statins in 25.7% of 1,404 African Americans who were deemed statin eligible by American College of Cardiology/American Heart Association guidelines.
Data source: Prospective, community-based study of 2,812 African American subjects in Mississippi – aged 40-75 years, mean age 55, 65.3% female, mean body mass index 31.6 kg/m2 – tracked for median of 10 years; 1,743 underwent computed tomography.
Disclosures: The National Heart, Lung, and Blood Institute and the National Institute on Minority Health and Health Disparities funded the study. One author reported funding from a National Institutes of Health grant. The others had no disclosures.
Trial supports FFR-guided complete revascularization during PCI for STEMI
WASHINGTON – Using fractional flow reserve (FFR) to revascularize noninfarct coronary arteries during percutaneous coronary intervention (PCI) significantly reduced the subsequent 1-year risk of major adverse cardiovascular events among patients with ST-segment myocardial infarction and multivessel disease, according to the results of a randomized, multicenter trial.
Only 23 patients (8%) who underwent complete FFR-guided revascularization died or had a nonfatal myocardial infarction, cerebrovascular event, or repeat revascularization within a year of treatment, compared with 121 (20.5%) patients who underwent infarct-only treatment (hazard ratio, 0.35; 95% confidence interval, 0.22-0.55; P less than .001), Pieter C. Smits, MD, PhD, reported during a late-breaker session at the annual meeting of the American College of Cardiology.
Importantly, coronary angiography overestimated the physiological significance of noninfart lesions in the study, the researchers wrote. About half of noninfarct lesions that were considered significant on angiography had FFR values above 0.80, meaning that they were not physiologically significant.
Some 50% of patients with acute ST-segment elevation myocardial infarction (STEMI) have severe stenotic lesions of noninfarct coronary arteries. These lesions often are managed conservatively, but two recent randomized trials have challenged this approach, tying preventive stent placement to lower rates of subsequent adverse events. However, both studies based the decision to use stents on angiographic appearance, not symptoms or ischemia, even though angiography can fail to accurately estimate the functional severity of a lesion, the investigators wrote. For stable patients, using FFR to guide revascularization instead can prevent adverse events compared with angiography or conservative management, they added.
To more rigorously compare FFR-guided revascularization of noninfarct coronary arteries with infarct-only treatment, the researchers randomly assigned 885 adults with acute STEMI and multivessel disease to one of these two approaches during primary PCI. A total of 295 patients underwent FFR-guided complete revascularization, and 590 underwent infarct-only treatment plus FFR evaluation of noninfarct-artery lesions.
Compared with infarct-only treatment, complete revascularization was associated with lower, but statistically similar, rates of mortality (1.7% vs. 1.4%; HR, 0.80; 95% CI, 0.25-2.6; P = .7), nonfatal myocardial infarction (4.7% vs. 2.4%; HR, 0.5; 95% CI, 0.2-1.1; P = .1), and cerebrovascular events (0.7% vs. 0%). The study lacked power to detect differences in rates of these uncommon events, the researchers noted.
In the infarct-only treatment group, stable or unstable angina accounted for most repeat revascularizations, about 80% of which were clinically indicated based on the study protocol, according to the researchers. Performing FFR-guided revascularization during primary PCI prevents sequential catheterizations and can potentially save costs by reducing predischarge stress tests, they commented. In their study, 12% of patients in the infarct-only group underwent stress tests, compared with 7% of those who underwent FFR-guided revascularization (P = .03).
Two patients experienced a serious adverse event related to FFR, the investigators noted. In one case, the FFR wire caused a dissection in the noninfarcted right coronary artery. The artery subsequently infarcted and the patient died in the hospital. Another patient developed an occlusion of the noninfarcted left anterior descending coronary artery. The patient developed ST-segment elevation and recurrent chest pain, but underwent successful PCI of the artery. There were no other adverse events except for brief episodes of atrioventricular conduction delay and episodes of moderate hypotension, they wrote.
This was an open-label study, and it is possible that patients and physicians in the infarct-only group were biased toward subsequent revascularizations because they knew the angiography results, the researchers also noted.
Maasstad Cardiovascular Research funded the study with unrestricted grants from Abbott Vascular and St. Jude Medical. Dr. Smits disclosed grant support from Abbott Vascular and St. Jude Medical, and grants support and personal fees from both entities outside the submitted work.
WASHINGTON – Using fractional flow reserve (FFR) to revascularize noninfarct coronary arteries during percutaneous coronary intervention (PCI) significantly reduced the subsequent 1-year risk of major adverse cardiovascular events among patients with ST-segment myocardial infarction and multivessel disease, according to the results of a randomized, multicenter trial.
Only 23 patients (8%) who underwent complete FFR-guided revascularization died or had a nonfatal myocardial infarction, cerebrovascular event, or repeat revascularization within a year of treatment, compared with 121 (20.5%) patients who underwent infarct-only treatment (hazard ratio, 0.35; 95% confidence interval, 0.22-0.55; P less than .001), Pieter C. Smits, MD, PhD, reported during a late-breaker session at the annual meeting of the American College of Cardiology.
Importantly, coronary angiography overestimated the physiological significance of noninfart lesions in the study, the researchers wrote. About half of noninfarct lesions that were considered significant on angiography had FFR values above 0.80, meaning that they were not physiologically significant.
Some 50% of patients with acute ST-segment elevation myocardial infarction (STEMI) have severe stenotic lesions of noninfarct coronary arteries. These lesions often are managed conservatively, but two recent randomized trials have challenged this approach, tying preventive stent placement to lower rates of subsequent adverse events. However, both studies based the decision to use stents on angiographic appearance, not symptoms or ischemia, even though angiography can fail to accurately estimate the functional severity of a lesion, the investigators wrote. For stable patients, using FFR to guide revascularization instead can prevent adverse events compared with angiography or conservative management, they added.
To more rigorously compare FFR-guided revascularization of noninfarct coronary arteries with infarct-only treatment, the researchers randomly assigned 885 adults with acute STEMI and multivessel disease to one of these two approaches during primary PCI. A total of 295 patients underwent FFR-guided complete revascularization, and 590 underwent infarct-only treatment plus FFR evaluation of noninfarct-artery lesions.
Compared with infarct-only treatment, complete revascularization was associated with lower, but statistically similar, rates of mortality (1.7% vs. 1.4%; HR, 0.80; 95% CI, 0.25-2.6; P = .7), nonfatal myocardial infarction (4.7% vs. 2.4%; HR, 0.5; 95% CI, 0.2-1.1; P = .1), and cerebrovascular events (0.7% vs. 0%). The study lacked power to detect differences in rates of these uncommon events, the researchers noted.
In the infarct-only treatment group, stable or unstable angina accounted for most repeat revascularizations, about 80% of which were clinically indicated based on the study protocol, according to the researchers. Performing FFR-guided revascularization during primary PCI prevents sequential catheterizations and can potentially save costs by reducing predischarge stress tests, they commented. In their study, 12% of patients in the infarct-only group underwent stress tests, compared with 7% of those who underwent FFR-guided revascularization (P = .03).
Two patients experienced a serious adverse event related to FFR, the investigators noted. In one case, the FFR wire caused a dissection in the noninfarcted right coronary artery. The artery subsequently infarcted and the patient died in the hospital. Another patient developed an occlusion of the noninfarcted left anterior descending coronary artery. The patient developed ST-segment elevation and recurrent chest pain, but underwent successful PCI of the artery. There were no other adverse events except for brief episodes of atrioventricular conduction delay and episodes of moderate hypotension, they wrote.
This was an open-label study, and it is possible that patients and physicians in the infarct-only group were biased toward subsequent revascularizations because they knew the angiography results, the researchers also noted.
Maasstad Cardiovascular Research funded the study with unrestricted grants from Abbott Vascular and St. Jude Medical. Dr. Smits disclosed grant support from Abbott Vascular and St. Jude Medical, and grants support and personal fees from both entities outside the submitted work.
WASHINGTON – Using fractional flow reserve (FFR) to revascularize noninfarct coronary arteries during percutaneous coronary intervention (PCI) significantly reduced the subsequent 1-year risk of major adverse cardiovascular events among patients with ST-segment myocardial infarction and multivessel disease, according to the results of a randomized, multicenter trial.
Only 23 patients (8%) who underwent complete FFR-guided revascularization died or had a nonfatal myocardial infarction, cerebrovascular event, or repeat revascularization within a year of treatment, compared with 121 (20.5%) patients who underwent infarct-only treatment (hazard ratio, 0.35; 95% confidence interval, 0.22-0.55; P less than .001), Pieter C. Smits, MD, PhD, reported during a late-breaker session at the annual meeting of the American College of Cardiology.
Importantly, coronary angiography overestimated the physiological significance of noninfart lesions in the study, the researchers wrote. About half of noninfarct lesions that were considered significant on angiography had FFR values above 0.80, meaning that they were not physiologically significant.
Some 50% of patients with acute ST-segment elevation myocardial infarction (STEMI) have severe stenotic lesions of noninfarct coronary arteries. These lesions often are managed conservatively, but two recent randomized trials have challenged this approach, tying preventive stent placement to lower rates of subsequent adverse events. However, both studies based the decision to use stents on angiographic appearance, not symptoms or ischemia, even though angiography can fail to accurately estimate the functional severity of a lesion, the investigators wrote. For stable patients, using FFR to guide revascularization instead can prevent adverse events compared with angiography or conservative management, they added.
To more rigorously compare FFR-guided revascularization of noninfarct coronary arteries with infarct-only treatment, the researchers randomly assigned 885 adults with acute STEMI and multivessel disease to one of these two approaches during primary PCI. A total of 295 patients underwent FFR-guided complete revascularization, and 590 underwent infarct-only treatment plus FFR evaluation of noninfarct-artery lesions.
Compared with infarct-only treatment, complete revascularization was associated with lower, but statistically similar, rates of mortality (1.7% vs. 1.4%; HR, 0.80; 95% CI, 0.25-2.6; P = .7), nonfatal myocardial infarction (4.7% vs. 2.4%; HR, 0.5; 95% CI, 0.2-1.1; P = .1), and cerebrovascular events (0.7% vs. 0%). The study lacked power to detect differences in rates of these uncommon events, the researchers noted.
In the infarct-only treatment group, stable or unstable angina accounted for most repeat revascularizations, about 80% of which were clinically indicated based on the study protocol, according to the researchers. Performing FFR-guided revascularization during primary PCI prevents sequential catheterizations and can potentially save costs by reducing predischarge stress tests, they commented. In their study, 12% of patients in the infarct-only group underwent stress tests, compared with 7% of those who underwent FFR-guided revascularization (P = .03).
Two patients experienced a serious adverse event related to FFR, the investigators noted. In one case, the FFR wire caused a dissection in the noninfarcted right coronary artery. The artery subsequently infarcted and the patient died in the hospital. Another patient developed an occlusion of the noninfarcted left anterior descending coronary artery. The patient developed ST-segment elevation and recurrent chest pain, but underwent successful PCI of the artery. There were no other adverse events except for brief episodes of atrioventricular conduction delay and episodes of moderate hypotension, they wrote.
This was an open-label study, and it is possible that patients and physicians in the infarct-only group were biased toward subsequent revascularizations because they knew the angiography results, the researchers also noted.
Maasstad Cardiovascular Research funded the study with unrestricted grants from Abbott Vascular and St. Jude Medical. Dr. Smits disclosed grant support from Abbott Vascular and St. Jude Medical, and grants support and personal fees from both entities outside the submitted work.
FROM ACC 17
Key clinical point:
Major finding: Only 23 patients (8%) who underwent complete FFR-guided revascularization died or had a nonfatal myocardial infarction, cerebrovascular event, or repeat revascularization within a year of treatment, compared with 121 (20.5%) patients who underwent infarct-only treatment (HR, 0.35; 95% CI, 0.22-0.55; P less than .001).
Data source: A prospective, multicenter, open-label clinical trial of 885 adults with acute STEMI and multivessel disease.
Disclosures: Maasstad Cardiovascular Research funded the study with unrestricted grants from Abbott Vascular and St. Jude Medical. Dr. Smits disclosed grant support from Abbott Vascular and St. Jude Medical, and grant support and personal fees from both entities outside the submitted work.
Moderate exercise benefits hypertrophic cardiomyopathy patients
WASHINGTON – A regimen of moderately intense exercise for 16 weeks produced no adverse effects and led to a clinically meaningful improvement in exercise capacity in a multicenter, randomized trial involving 136 patients with hypertrophic cardiomyopathy.
While finding that regular exercise produced a statistically significant improvement, compared with control patients fulfilled the study’s primary endpoint, it was perhaps as important that patients with hypertrophic cardiomyopathy (HCM) randomized to the exercise arm experienced no ill effects, a finding that bucked conventional wisdom that, once diagnosed, HCM patients must adhere to a largely inactive lifestyle.
“I see patients with HCM who tell me that, when they were first diagnosed, they were told by their physician not to do anything at all,” said Dr. Saberi, a cardiologist at the University of Michigan in Arbor. Although she cautioned that the findings from this modestly sized trial cannot prove that exercise is safe for HMC patients – something that would require randomizing more than 2,000 patients and following them for about 3 years – the findings provide some level of reassurance that regular, moderately intense exercise as simple as walking can benefit patients and likely not cause any problems. “We saw no signal of harm,” she stressed in an interview. “I would recommend moderate-intensity, regular exercise. Physicians can feel comfortable using the exercise prescription” used in the study, she advised.
Concurrently with Dr. Saberi’s report at the meeting, the results also appeared in an article published online (JAMA. 2017 Mar 17. doi: 10.1001/jama.2017.2503).
The Study of Exercise Training in Hypertrophic Cardiomyopathy (RESET-HCM) ran during 2010-2015 at the University of Michigan and Stanford University, and enrolled 136 patients 18-80 years old diagnosed with HCM but without more severe manifestations such as a history of exercise-induced syncope or ventricular arrhythmia, a left ventricular ejection fraction less than 55%, recent clinical decompensation, or a history of a severe hypotensive response to exercise. Enrolled patients averaged about 50 years old, their baseline peak oxygen consumption, VO2, was about 22 mL/kg per min, and their maximal ventricular wall thickness was about 21 mm.
Following a comprehensive baseline heart function and imaging assessment, including a cardiopulmonary exercise test, the 67 patients in the intervention arm received an individualized exercise prescription based on their heart rate reserve. At a minimum, they started with three exercise sessions per week lasting at least 20 minutes on their own, a regimen designed to bring them to 60% of their heart rate reserve. Their prescription gradually increased to four to seven exercise periods weekly lasting up to 60 minutes and designed to bring them to 70% of their heart rate reserve. Although most patients accomplished this through walking, some engaged in activities that included cycling, swimming, jogging, or elliptical training. The researchers told the 69 control patients to continue doing their usual activities. Among the patients who entered the study, 57 in the exercise group and 56 controls remained for the full 16 weeks and had a complete final assessment.
After 16 weeks, the average change in peak VO2, was 1.35 mL/kg per min in the intervention group and 0.08 mL/kg per min in the control patients, a statistically significant difference for the primary endpoint and a 6% increase in exercise capacity, compared with baseline for the intervention group. Dr. Saberi noted that, in a prior study of patients with chronic heart failure, a 6% increase in peak VO2 linked with an 8% decrease in cardiovascular mortality of heart failure hospitalization.
This result is “a glimmer of hope for using exercise in HCM patients,” she said. “There are no other disease-modifying treatments for HCM, so this is the first ‘treatment’ to have any impact on the disease.”
The patients who exercised had no identified major adverse effects or changes in cardiac morphology after 16 weeks. Assessment of physical function quality of life using the SF-36v2 showed an average 8-point improvement in the patients who exercised, compared with the controls. In addition, “a lot of patients in the exercise group told us that they felt better,” Dr. Saberi said.
Because patients with HCM are often advised to limit their activity, the consequence is “we increasingly see HCM patients who are obese and have complications such as sleep apnea and atrial fibrillation. Patients are even fearful of going up and down stairs.” She stressed the simplicity and ease of the intervention she and her colleagues tested, which can involve nothing more than regular, daily walks of 20 minutes or more. Dr. Saberi advised tailoring the intensity and frequency of the exercise intervention to each patient and avoiding having the patient push beyond what they find comfortable.
A multicenter U.S. registry, the Lifestyle and Exercise in Hypertrophic Cardiomyopathy Study (LIVE-HCM), is now enrolling HCM patients that should eventually follow enough patients for a long enough period of time to definitely prove whether moderate exercise is safe for HCM patients, but the results will not be available for several more years, Dr. Saberi said. A recent analysis estimated that one in every 200 adults has HCM (J Am Coll Cardiol. 2015 Mar 31;65[12]:1249-54), which means the disease likely affects more than one million Americans.
[email protected]
On Twitter @mitchelzoler
WASHINGTON – A regimen of moderately intense exercise for 16 weeks produced no adverse effects and led to a clinically meaningful improvement in exercise capacity in a multicenter, randomized trial involving 136 patients with hypertrophic cardiomyopathy.
While finding that regular exercise produced a statistically significant improvement, compared with control patients fulfilled the study’s primary endpoint, it was perhaps as important that patients with hypertrophic cardiomyopathy (HCM) randomized to the exercise arm experienced no ill effects, a finding that bucked conventional wisdom that, once diagnosed, HCM patients must adhere to a largely inactive lifestyle.
“I see patients with HCM who tell me that, when they were first diagnosed, they were told by their physician not to do anything at all,” said Dr. Saberi, a cardiologist at the University of Michigan in Arbor. Although she cautioned that the findings from this modestly sized trial cannot prove that exercise is safe for HMC patients – something that would require randomizing more than 2,000 patients and following them for about 3 years – the findings provide some level of reassurance that regular, moderately intense exercise as simple as walking can benefit patients and likely not cause any problems. “We saw no signal of harm,” she stressed in an interview. “I would recommend moderate-intensity, regular exercise. Physicians can feel comfortable using the exercise prescription” used in the study, she advised.
Concurrently with Dr. Saberi’s report at the meeting, the results also appeared in an article published online (JAMA. 2017 Mar 17. doi: 10.1001/jama.2017.2503).
The Study of Exercise Training in Hypertrophic Cardiomyopathy (RESET-HCM) ran during 2010-2015 at the University of Michigan and Stanford University, and enrolled 136 patients 18-80 years old diagnosed with HCM but without more severe manifestations such as a history of exercise-induced syncope or ventricular arrhythmia, a left ventricular ejection fraction less than 55%, recent clinical decompensation, or a history of a severe hypotensive response to exercise. Enrolled patients averaged about 50 years old, their baseline peak oxygen consumption, VO2, was about 22 mL/kg per min, and their maximal ventricular wall thickness was about 21 mm.
Following a comprehensive baseline heart function and imaging assessment, including a cardiopulmonary exercise test, the 67 patients in the intervention arm received an individualized exercise prescription based on their heart rate reserve. At a minimum, they started with three exercise sessions per week lasting at least 20 minutes on their own, a regimen designed to bring them to 60% of their heart rate reserve. Their prescription gradually increased to four to seven exercise periods weekly lasting up to 60 minutes and designed to bring them to 70% of their heart rate reserve. Although most patients accomplished this through walking, some engaged in activities that included cycling, swimming, jogging, or elliptical training. The researchers told the 69 control patients to continue doing their usual activities. Among the patients who entered the study, 57 in the exercise group and 56 controls remained for the full 16 weeks and had a complete final assessment.
After 16 weeks, the average change in peak VO2, was 1.35 mL/kg per min in the intervention group and 0.08 mL/kg per min in the control patients, a statistically significant difference for the primary endpoint and a 6% increase in exercise capacity, compared with baseline for the intervention group. Dr. Saberi noted that, in a prior study of patients with chronic heart failure, a 6% increase in peak VO2 linked with an 8% decrease in cardiovascular mortality of heart failure hospitalization.
This result is “a glimmer of hope for using exercise in HCM patients,” she said. “There are no other disease-modifying treatments for HCM, so this is the first ‘treatment’ to have any impact on the disease.”
The patients who exercised had no identified major adverse effects or changes in cardiac morphology after 16 weeks. Assessment of physical function quality of life using the SF-36v2 showed an average 8-point improvement in the patients who exercised, compared with the controls. In addition, “a lot of patients in the exercise group told us that they felt better,” Dr. Saberi said.
Because patients with HCM are often advised to limit their activity, the consequence is “we increasingly see HCM patients who are obese and have complications such as sleep apnea and atrial fibrillation. Patients are even fearful of going up and down stairs.” She stressed the simplicity and ease of the intervention she and her colleagues tested, which can involve nothing more than regular, daily walks of 20 minutes or more. Dr. Saberi advised tailoring the intensity and frequency of the exercise intervention to each patient and avoiding having the patient push beyond what they find comfortable.
A multicenter U.S. registry, the Lifestyle and Exercise in Hypertrophic Cardiomyopathy Study (LIVE-HCM), is now enrolling HCM patients that should eventually follow enough patients for a long enough period of time to definitely prove whether moderate exercise is safe for HCM patients, but the results will not be available for several more years, Dr. Saberi said. A recent analysis estimated that one in every 200 adults has HCM (J Am Coll Cardiol. 2015 Mar 31;65[12]:1249-54), which means the disease likely affects more than one million Americans.
[email protected]
On Twitter @mitchelzoler
WASHINGTON – A regimen of moderately intense exercise for 16 weeks produced no adverse effects and led to a clinically meaningful improvement in exercise capacity in a multicenter, randomized trial involving 136 patients with hypertrophic cardiomyopathy.
While finding that regular exercise produced a statistically significant improvement, compared with control patients fulfilled the study’s primary endpoint, it was perhaps as important that patients with hypertrophic cardiomyopathy (HCM) randomized to the exercise arm experienced no ill effects, a finding that bucked conventional wisdom that, once diagnosed, HCM patients must adhere to a largely inactive lifestyle.
“I see patients with HCM who tell me that, when they were first diagnosed, they were told by their physician not to do anything at all,” said Dr. Saberi, a cardiologist at the University of Michigan in Arbor. Although she cautioned that the findings from this modestly sized trial cannot prove that exercise is safe for HMC patients – something that would require randomizing more than 2,000 patients and following them for about 3 years – the findings provide some level of reassurance that regular, moderately intense exercise as simple as walking can benefit patients and likely not cause any problems. “We saw no signal of harm,” she stressed in an interview. “I would recommend moderate-intensity, regular exercise. Physicians can feel comfortable using the exercise prescription” used in the study, she advised.
Concurrently with Dr. Saberi’s report at the meeting, the results also appeared in an article published online (JAMA. 2017 Mar 17. doi: 10.1001/jama.2017.2503).
The Study of Exercise Training in Hypertrophic Cardiomyopathy (RESET-HCM) ran during 2010-2015 at the University of Michigan and Stanford University, and enrolled 136 patients 18-80 years old diagnosed with HCM but without more severe manifestations such as a history of exercise-induced syncope or ventricular arrhythmia, a left ventricular ejection fraction less than 55%, recent clinical decompensation, or a history of a severe hypotensive response to exercise. Enrolled patients averaged about 50 years old, their baseline peak oxygen consumption, VO2, was about 22 mL/kg per min, and their maximal ventricular wall thickness was about 21 mm.
Following a comprehensive baseline heart function and imaging assessment, including a cardiopulmonary exercise test, the 67 patients in the intervention arm received an individualized exercise prescription based on their heart rate reserve. At a minimum, they started with three exercise sessions per week lasting at least 20 minutes on their own, a regimen designed to bring them to 60% of their heart rate reserve. Their prescription gradually increased to four to seven exercise periods weekly lasting up to 60 minutes and designed to bring them to 70% of their heart rate reserve. Although most patients accomplished this through walking, some engaged in activities that included cycling, swimming, jogging, or elliptical training. The researchers told the 69 control patients to continue doing their usual activities. Among the patients who entered the study, 57 in the exercise group and 56 controls remained for the full 16 weeks and had a complete final assessment.
After 16 weeks, the average change in peak VO2, was 1.35 mL/kg per min in the intervention group and 0.08 mL/kg per min in the control patients, a statistically significant difference for the primary endpoint and a 6% increase in exercise capacity, compared with baseline for the intervention group. Dr. Saberi noted that, in a prior study of patients with chronic heart failure, a 6% increase in peak VO2 linked with an 8% decrease in cardiovascular mortality of heart failure hospitalization.
This result is “a glimmer of hope for using exercise in HCM patients,” she said. “There are no other disease-modifying treatments for HCM, so this is the first ‘treatment’ to have any impact on the disease.”
The patients who exercised had no identified major adverse effects or changes in cardiac morphology after 16 weeks. Assessment of physical function quality of life using the SF-36v2 showed an average 8-point improvement in the patients who exercised, compared with the controls. In addition, “a lot of patients in the exercise group told us that they felt better,” Dr. Saberi said.
Because patients with HCM are often advised to limit their activity, the consequence is “we increasingly see HCM patients who are obese and have complications such as sleep apnea and atrial fibrillation. Patients are even fearful of going up and down stairs.” She stressed the simplicity and ease of the intervention she and her colleagues tested, which can involve nothing more than regular, daily walks of 20 minutes or more. Dr. Saberi advised tailoring the intensity and frequency of the exercise intervention to each patient and avoiding having the patient push beyond what they find comfortable.
A multicenter U.S. registry, the Lifestyle and Exercise in Hypertrophic Cardiomyopathy Study (LIVE-HCM), is now enrolling HCM patients that should eventually follow enough patients for a long enough period of time to definitely prove whether moderate exercise is safe for HCM patients, but the results will not be available for several more years, Dr. Saberi said. A recent analysis estimated that one in every 200 adults has HCM (J Am Coll Cardiol. 2015 Mar 31;65[12]:1249-54), which means the disease likely affects more than one million Americans.
[email protected]
On Twitter @mitchelzoler
AT ACC 17
Key clinical point:
Major finding: Average exercise capacity, peak VO2, increased by 1.27 mL/kg per min in exercising patients compared with nonexercising controls.
Data source: RESET-HCM, a multicenter, randomized trial with 136 hypertrophic cardiomyopathy patients.
Disclosures: Dr. Saberi had no disclosures.
VIDEO: Clear food labels may improve healthy habits
WASHINGTON – Application clear graphic nutrition labels on the front of packaged foods could help patients make healthier food choices, according to a study out of the George Institute of Global Health, Sydney.
Bruce Neal, PhD, senior director of the food policy division at the institute, and his colleagues asked 1,578 study participants to use a smart phone scanner to record the packaged foods they bought over the course of a week. Nutrition information from those scans was used to derive a nutrient profile score and plugged into four different food labeling systems on a randomized basis:
- Health Star Rating (HSR). A graphic label that gives the product from one to five stars.
- Multi-color Traffic Light (MTD). A graphic label that advises the participant to stop, use caution, or go.
- Daily Intake Guide (DIG). A graphic label that presents important nutrients in larger numbers.
- Nutrient Information Panel (NIP). A chart-based label listing nutrient values, similar to the U.S. Nutrition Facts label.
Nutrient information provided by HSR was found to be noninferior to the alternatives, Dr. Neal said at the annual meeting of the American College of Cardiology.
HSR earned a superiority score of 0.38, 0.1, and 0.23 when compared with MTL, DIG, and NIP labels, respectively, according to the study.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
Dr. Neal attributed the “unimpressive results” in part to the use of the smart phone interface.
“The trial used a smart phone design, which is a suboptimal surrogate, compared with printed on every pack. In the real world it would work better,” he said in a video interview.
While overall mean nutrition information was found to be not inferior, HSR scored significantly higher that the alternatives in user perception. In understandability, HSR scored 0.62 (P = .005), 1.02 (P less than .001), and 0.22 (P equal .32), compared with MTL, DIG, and NIP, respectively.
HSR also scored significantly higher among participants in “value of having on all food packs,” especially against DIG, scoring 0.70 (P = .002).
“It is absolutely clear that Health Star Rating is preferred to any of the other formats by consumers,” Dr. Neal said. “It is probably [also] fair to say Health Star is now the Australian government’s strongest choice.”
Participants were on average 38 years old, overwhelmingly female (84%), and well educated with 72% reporting a tertiary education or higher. Despite this more affluent and educated population, Dr. Neal and his colleagues believe that HSR can be used with any group.
“We are embarking on a project to roll out this smart phone application with a different interface suited to other, disadvantaged groups,” Dr. Neal said. “We are also working with the [Australian] state government to use Health Star for fast food restaurants and school canteens, as well as government procurement for use in hospitals and prisons.”
The study was limited by its reliance on participants to record their own purchases, Dr. Neal added.
[email protected]
On Twitter @EAZtweets
WASHINGTON – Application clear graphic nutrition labels on the front of packaged foods could help patients make healthier food choices, according to a study out of the George Institute of Global Health, Sydney.
Bruce Neal, PhD, senior director of the food policy division at the institute, and his colleagues asked 1,578 study participants to use a smart phone scanner to record the packaged foods they bought over the course of a week. Nutrition information from those scans was used to derive a nutrient profile score and plugged into four different food labeling systems on a randomized basis:
- Health Star Rating (HSR). A graphic label that gives the product from one to five stars.
- Multi-color Traffic Light (MTD). A graphic label that advises the participant to stop, use caution, or go.
- Daily Intake Guide (DIG). A graphic label that presents important nutrients in larger numbers.
- Nutrient Information Panel (NIP). A chart-based label listing nutrient values, similar to the U.S. Nutrition Facts label.
Nutrient information provided by HSR was found to be noninferior to the alternatives, Dr. Neal said at the annual meeting of the American College of Cardiology.
HSR earned a superiority score of 0.38, 0.1, and 0.23 when compared with MTL, DIG, and NIP labels, respectively, according to the study.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
Dr. Neal attributed the “unimpressive results” in part to the use of the smart phone interface.
“The trial used a smart phone design, which is a suboptimal surrogate, compared with printed on every pack. In the real world it would work better,” he said in a video interview.
While overall mean nutrition information was found to be not inferior, HSR scored significantly higher that the alternatives in user perception. In understandability, HSR scored 0.62 (P = .005), 1.02 (P less than .001), and 0.22 (P equal .32), compared with MTL, DIG, and NIP, respectively.
HSR also scored significantly higher among participants in “value of having on all food packs,” especially against DIG, scoring 0.70 (P = .002).
“It is absolutely clear that Health Star Rating is preferred to any of the other formats by consumers,” Dr. Neal said. “It is probably [also] fair to say Health Star is now the Australian government’s strongest choice.”
Participants were on average 38 years old, overwhelmingly female (84%), and well educated with 72% reporting a tertiary education or higher. Despite this more affluent and educated population, Dr. Neal and his colleagues believe that HSR can be used with any group.
“We are embarking on a project to roll out this smart phone application with a different interface suited to other, disadvantaged groups,” Dr. Neal said. “We are also working with the [Australian] state government to use Health Star for fast food restaurants and school canteens, as well as government procurement for use in hospitals and prisons.”
The study was limited by its reliance on participants to record their own purchases, Dr. Neal added.
[email protected]
On Twitter @EAZtweets
WASHINGTON – Application clear graphic nutrition labels on the front of packaged foods could help patients make healthier food choices, according to a study out of the George Institute of Global Health, Sydney.
Bruce Neal, PhD, senior director of the food policy division at the institute, and his colleagues asked 1,578 study participants to use a smart phone scanner to record the packaged foods they bought over the course of a week. Nutrition information from those scans was used to derive a nutrient profile score and plugged into four different food labeling systems on a randomized basis:
- Health Star Rating (HSR). A graphic label that gives the product from one to five stars.
- Multi-color Traffic Light (MTD). A graphic label that advises the participant to stop, use caution, or go.
- Daily Intake Guide (DIG). A graphic label that presents important nutrients in larger numbers.
- Nutrient Information Panel (NIP). A chart-based label listing nutrient values, similar to the U.S. Nutrition Facts label.
Nutrient information provided by HSR was found to be noninferior to the alternatives, Dr. Neal said at the annual meeting of the American College of Cardiology.
HSR earned a superiority score of 0.38, 0.1, and 0.23 when compared with MTL, DIG, and NIP labels, respectively, according to the study.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
Dr. Neal attributed the “unimpressive results” in part to the use of the smart phone interface.
“The trial used a smart phone design, which is a suboptimal surrogate, compared with printed on every pack. In the real world it would work better,” he said in a video interview.
While overall mean nutrition information was found to be not inferior, HSR scored significantly higher that the alternatives in user perception. In understandability, HSR scored 0.62 (P = .005), 1.02 (P less than .001), and 0.22 (P equal .32), compared with MTL, DIG, and NIP, respectively.
HSR also scored significantly higher among participants in “value of having on all food packs,” especially against DIG, scoring 0.70 (P = .002).
“It is absolutely clear that Health Star Rating is preferred to any of the other formats by consumers,” Dr. Neal said. “It is probably [also] fair to say Health Star is now the Australian government’s strongest choice.”
Participants were on average 38 years old, overwhelmingly female (84%), and well educated with 72% reporting a tertiary education or higher. Despite this more affluent and educated population, Dr. Neal and his colleagues believe that HSR can be used with any group.
“We are embarking on a project to roll out this smart phone application with a different interface suited to other, disadvantaged groups,” Dr. Neal said. “We are also working with the [Australian] state government to use Health Star for fast food restaurants and school canteens, as well as government procurement for use in hospitals and prisons.”
The study was limited by its reliance on participants to record their own purchases, Dr. Neal added.
[email protected]
On Twitter @EAZtweets
AT ACC 17
Older TAVR implant devices significantly less effective than newer ones in bicuspid AS patients
Using transcatheter aortic valve replacement (TAVR) to treat bicuspid aortic valve stenosis (AS) can be significantly less effective than using TAVR to treat tricuspid AS, according to the findings of a new study presented at the annual meeting of the American College of Cardiology and published simultaneously in the Journal of the American College of Cardiology.
“There is a paucity of data comparing the clinical outcomes of TAVR in bicuspid and tricuspid AS,” wrote the authors of the study, led by Sung-Han Yoon, MD, of the Cedars-Sinai Heart Institute in Los Angeles. “Given the increasing frequency of bicuspid AS in younger patients, coupled with the worldwide shift of treating younger and lower–surgical-risk patients with TAVR, the clinical outcomes of TAVR in bicuspid AS warrants special attention.”
Dr. Yoon and his coinvestigators began by collecting data from the Bicuspid AS TAVR registry, which began in December 2013 and contains information on patients from 33 health care centers around the world. Patients who entered the database prior to the initiation of the study were screened retroactively, while those who joined afterward were followed prospectively.
Eventually, 561 bicuspid AS patients were included in the study, out of a total of 576 that were treated between April 2005 and May 2016. Twelve centers also performed tricuspid AS, with investigators able to collect data on 5,900 patients who underwent the procedure during the same period of time. Ultimately, 4,546 were included in the study.
“Given the differences in baseline clinical, echocardiographic, and procedural characteristics between patients with bicuspid and tricuspid AS, propensity-score matching was applied to identify a cohort of patients with similar baseline characteristics, and thus clinical outcomes of propensity-score matched cohorts were compared,” the authors explained.
Variables used when establishing propensity-score matches included age, sex, New York Heart Association functional class III or IV, the presence of certain conditions such as chronic lung disease and diabetes, and procedural data. Dr. Yoon and his colleagues were able to create 546 pairs of matched patients between the bicuspid AS and tricuspid AS cohorts.
The devices implanted in subjects also underwent classification by the investigators, either as early-generation or new-generation devices. The former consisted of Sapien XT and CoreValve devices, while Sapien 3, Lotus, and Evolut R devices comprised the latter classification. A total of 320 bicuspid AS and 321 tricuspid AS patients received early-generation implant devices, with 226 and 225 patients, respectively, receiving new-generation devices.
Devices were less successful in bicuspid AS patients versus tricuspid AS patients: 85.3% and 91.4%, respectively (P = .002). Furthermore, a significantly higher rate of bicuspid AS patients had to be converted to surgery, compared with tricuspid AS patients: 2.0% and 0.2%, respectively (P = .006). Early-generation implant devices had considerably higher rates of issues in bicuspid AS patients, with 4.5% of those receiving Sapien XT experiencing aortic root injury and 0% of tricuspid AS patients with the same device having the same problem (P = .015). Bicuspid AS patients who received the CoreValve implant experienced paravalvular leak 19.4% of the time, compared with 10.5% in tricuspid AS patients (P = .02); these leaks were classified as “moderate to severe.”
“In addition, patients with bicuspid AS had more frequent second valve implantation (11.6% vs. 2.9%; P = .002) [and] subsequent lower device success rates (72.1% vs. 86.0%; P = .002) than those with tricuspid AS when receiving the CoreValve,” the authors noted. “However, there were no significant differences in these adverse procedural events between groups when receiving the Sapien 3 and Lotus.”
There were also no significant differences between the bicuspid and tricuspid AS in terms of mortality rates. At 2 years postoperation, all-cause mortality rates were 17.2% for bicuspid AS patients and 19.4% for tricuspid AS patients, regardless of the type of device implant (P = .28). When comparing early and new-generation devices, results were similarly nonsignificant: early-generation bicuspid vs. tricuspid AS all-cause mortality rates were 14.5% and 13.7%, respectively (P = .80) and 4.5% vs. 7.4% (P = .64) for new-generation devices.
“The present study is the first large-scale study that compared the safety, efficacy, and clinical outcomes of TAVR in patients with bicuspid and tricuspid AS,” Dr. Yoon and his colleagues noted, adding that, in regards to the disparity in device effectiveness, “The present study showed that the initial attempt of device advancement succeeded in overcoming the procedural limitations in tricuspid AS and now go beyond the challenges in treating bicuspid AS.”
No funding source for this study was disclosed. Dr. Yoon did not report any relevant financial disclosures, but several coauthors disclosed potentially relevant financial conflicts.
Using transcatheter aortic valve replacement (TAVR) to treat bicuspid aortic valve stenosis (AS) can be significantly less effective than using TAVR to treat tricuspid AS, according to the findings of a new study presented at the annual meeting of the American College of Cardiology and published simultaneously in the Journal of the American College of Cardiology.
“There is a paucity of data comparing the clinical outcomes of TAVR in bicuspid and tricuspid AS,” wrote the authors of the study, led by Sung-Han Yoon, MD, of the Cedars-Sinai Heart Institute in Los Angeles. “Given the increasing frequency of bicuspid AS in younger patients, coupled with the worldwide shift of treating younger and lower–surgical-risk patients with TAVR, the clinical outcomes of TAVR in bicuspid AS warrants special attention.”
Dr. Yoon and his coinvestigators began by collecting data from the Bicuspid AS TAVR registry, which began in December 2013 and contains information on patients from 33 health care centers around the world. Patients who entered the database prior to the initiation of the study were screened retroactively, while those who joined afterward were followed prospectively.
Eventually, 561 bicuspid AS patients were included in the study, out of a total of 576 that were treated between April 2005 and May 2016. Twelve centers also performed tricuspid AS, with investigators able to collect data on 5,900 patients who underwent the procedure during the same period of time. Ultimately, 4,546 were included in the study.
“Given the differences in baseline clinical, echocardiographic, and procedural characteristics between patients with bicuspid and tricuspid AS, propensity-score matching was applied to identify a cohort of patients with similar baseline characteristics, and thus clinical outcomes of propensity-score matched cohorts were compared,” the authors explained.
Variables used when establishing propensity-score matches included age, sex, New York Heart Association functional class III or IV, the presence of certain conditions such as chronic lung disease and diabetes, and procedural data. Dr. Yoon and his colleagues were able to create 546 pairs of matched patients between the bicuspid AS and tricuspid AS cohorts.
The devices implanted in subjects also underwent classification by the investigators, either as early-generation or new-generation devices. The former consisted of Sapien XT and CoreValve devices, while Sapien 3, Lotus, and Evolut R devices comprised the latter classification. A total of 320 bicuspid AS and 321 tricuspid AS patients received early-generation implant devices, with 226 and 225 patients, respectively, receiving new-generation devices.
Devices were less successful in bicuspid AS patients versus tricuspid AS patients: 85.3% and 91.4%, respectively (P = .002). Furthermore, a significantly higher rate of bicuspid AS patients had to be converted to surgery, compared with tricuspid AS patients: 2.0% and 0.2%, respectively (P = .006). Early-generation implant devices had considerably higher rates of issues in bicuspid AS patients, with 4.5% of those receiving Sapien XT experiencing aortic root injury and 0% of tricuspid AS patients with the same device having the same problem (P = .015). Bicuspid AS patients who received the CoreValve implant experienced paravalvular leak 19.4% of the time, compared with 10.5% in tricuspid AS patients (P = .02); these leaks were classified as “moderate to severe.”
“In addition, patients with bicuspid AS had more frequent second valve implantation (11.6% vs. 2.9%; P = .002) [and] subsequent lower device success rates (72.1% vs. 86.0%; P = .002) than those with tricuspid AS when receiving the CoreValve,” the authors noted. “However, there were no significant differences in these adverse procedural events between groups when receiving the Sapien 3 and Lotus.”
There were also no significant differences between the bicuspid and tricuspid AS in terms of mortality rates. At 2 years postoperation, all-cause mortality rates were 17.2% for bicuspid AS patients and 19.4% for tricuspid AS patients, regardless of the type of device implant (P = .28). When comparing early and new-generation devices, results were similarly nonsignificant: early-generation bicuspid vs. tricuspid AS all-cause mortality rates were 14.5% and 13.7%, respectively (P = .80) and 4.5% vs. 7.4% (P = .64) for new-generation devices.
“The present study is the first large-scale study that compared the safety, efficacy, and clinical outcomes of TAVR in patients with bicuspid and tricuspid AS,” Dr. Yoon and his colleagues noted, adding that, in regards to the disparity in device effectiveness, “The present study showed that the initial attempt of device advancement succeeded in overcoming the procedural limitations in tricuspid AS and now go beyond the challenges in treating bicuspid AS.”
No funding source for this study was disclosed. Dr. Yoon did not report any relevant financial disclosures, but several coauthors disclosed potentially relevant financial conflicts.
Using transcatheter aortic valve replacement (TAVR) to treat bicuspid aortic valve stenosis (AS) can be significantly less effective than using TAVR to treat tricuspid AS, according to the findings of a new study presented at the annual meeting of the American College of Cardiology and published simultaneously in the Journal of the American College of Cardiology.
“There is a paucity of data comparing the clinical outcomes of TAVR in bicuspid and tricuspid AS,” wrote the authors of the study, led by Sung-Han Yoon, MD, of the Cedars-Sinai Heart Institute in Los Angeles. “Given the increasing frequency of bicuspid AS in younger patients, coupled with the worldwide shift of treating younger and lower–surgical-risk patients with TAVR, the clinical outcomes of TAVR in bicuspid AS warrants special attention.”
Dr. Yoon and his coinvestigators began by collecting data from the Bicuspid AS TAVR registry, which began in December 2013 and contains information on patients from 33 health care centers around the world. Patients who entered the database prior to the initiation of the study were screened retroactively, while those who joined afterward were followed prospectively.
Eventually, 561 bicuspid AS patients were included in the study, out of a total of 576 that were treated between April 2005 and May 2016. Twelve centers also performed tricuspid AS, with investigators able to collect data on 5,900 patients who underwent the procedure during the same period of time. Ultimately, 4,546 were included in the study.
“Given the differences in baseline clinical, echocardiographic, and procedural characteristics between patients with bicuspid and tricuspid AS, propensity-score matching was applied to identify a cohort of patients with similar baseline characteristics, and thus clinical outcomes of propensity-score matched cohorts were compared,” the authors explained.
Variables used when establishing propensity-score matches included age, sex, New York Heart Association functional class III or IV, the presence of certain conditions such as chronic lung disease and diabetes, and procedural data. Dr. Yoon and his colleagues were able to create 546 pairs of matched patients between the bicuspid AS and tricuspid AS cohorts.
The devices implanted in subjects also underwent classification by the investigators, either as early-generation or new-generation devices. The former consisted of Sapien XT and CoreValve devices, while Sapien 3, Lotus, and Evolut R devices comprised the latter classification. A total of 320 bicuspid AS and 321 tricuspid AS patients received early-generation implant devices, with 226 and 225 patients, respectively, receiving new-generation devices.
Devices were less successful in bicuspid AS patients versus tricuspid AS patients: 85.3% and 91.4%, respectively (P = .002). Furthermore, a significantly higher rate of bicuspid AS patients had to be converted to surgery, compared with tricuspid AS patients: 2.0% and 0.2%, respectively (P = .006). Early-generation implant devices had considerably higher rates of issues in bicuspid AS patients, with 4.5% of those receiving Sapien XT experiencing aortic root injury and 0% of tricuspid AS patients with the same device having the same problem (P = .015). Bicuspid AS patients who received the CoreValve implant experienced paravalvular leak 19.4% of the time, compared with 10.5% in tricuspid AS patients (P = .02); these leaks were classified as “moderate to severe.”
“In addition, patients with bicuspid AS had more frequent second valve implantation (11.6% vs. 2.9%; P = .002) [and] subsequent lower device success rates (72.1% vs. 86.0%; P = .002) than those with tricuspid AS when receiving the CoreValve,” the authors noted. “However, there were no significant differences in these adverse procedural events between groups when receiving the Sapien 3 and Lotus.”
There were also no significant differences between the bicuspid and tricuspid AS in terms of mortality rates. At 2 years postoperation, all-cause mortality rates were 17.2% for bicuspid AS patients and 19.4% for tricuspid AS patients, regardless of the type of device implant (P = .28). When comparing early and new-generation devices, results were similarly nonsignificant: early-generation bicuspid vs. tricuspid AS all-cause mortality rates were 14.5% and 13.7%, respectively (P = .80) and 4.5% vs. 7.4% (P = .64) for new-generation devices.
“The present study is the first large-scale study that compared the safety, efficacy, and clinical outcomes of TAVR in patients with bicuspid and tricuspid AS,” Dr. Yoon and his colleagues noted, adding that, in regards to the disparity in device effectiveness, “The present study showed that the initial attempt of device advancement succeeded in overcoming the procedural limitations in tricuspid AS and now go beyond the challenges in treating bicuspid AS.”
No funding source for this study was disclosed. Dr. Yoon did not report any relevant financial disclosures, but several coauthors disclosed potentially relevant financial conflicts.
From ACC 17
Key clinical point:
Major finding: Bicuspid AS patients had significantly lower device success rates than those getting tricuspid AS: 85.3% vs. 91.4% (P = .002); also were more likely to convert to surgery: 2.0% vs. 0.2% (P = .006).
Data source: Matched cohort study of 561 bicuspid AS and 4,546 tricuspid AS patients; data collected both retrospectively and prospectively.
Disclosures: No funding source disclosed. Dr. Yoon reported no relevant disclosures.
Aspirin or rivaroxaban plus P2Y12 inhibitor equals 5% bleeding risk
Clinically significant bleeding in acute coronary patients was approximately 5% when their P2Y12 inhibitor treatment was combined with either rivaroxaban or with aspirin, based on data from a randomized, multicenter study of 3,037 adults.
The findings support the use of low-dose rivaroxaban as a safe strategy and an alternative to aspirin for postacute care of coronary syndromes, wrote E. Magnus Ohman, MD, of Duke University in Durham, N.C., and his colleagues.
The study was presented at the annual meeting of the American College of Cardiology and published simultaneously in the Lancet (2017. Mar 18. doi: org/10.1016/S0140-6736[17]30751-1).
The GEMINI ACS 1 trial included patients older than 18 years, who were randomized to P2Y12 with rivaroxaban or P2Y12 with aspirin within 10 days of admission for acute coronary syndrome events, from 371 clinical centers in 21 countries. The patients received 2.5 mg of low-dose rivaroxaban twice daily plus a P2Y12 inhibitor (clopidogrel or ticagrelor, based on national availability) or 100 mg of aspirin daily plus a P2Y12 inhibitor. Patients were assessed at 30, 90, 180, and 270 days.
Overall, 154 patients (5%) met the primary endpoint of thrombolysis in myocardial infarction (TIMI) of clinically significant bleeding – 80 patients (5%) in the rivaroxaban group and 74 (5%) in the aspirin group. Baseline demographics were not significantly different between the groups, and clinically significant bleeding was not significantly different among subgroups.
TIMI bleeding that required medical attention was the most common, occurring in 4% of each group. Both groups had a low frequency of severe or major bleeding based on the TIMI bleeding definitions, the researchers noted.
The composite ischemic endpoint of cardiovascular death, myocardial infarction, stroke, or definite stent thrombosis was 5% in both groups, and both groups had a similar frequency of all-cause mortality and of each of the composite ischemic elements. Rivaroxaban was associated with a higher occurrence of the ischemic composite endpoint in the first 30 days (hazard ratio, 1.48), but this difference was not statistically significant.
“Additionally, no significant interaction was noted for the risk of clinically significant bleeding by P2Y12 inhibitor strata (ticagrelor vs. clopidogrel), but these stratified bleeding analyses were exploratory and hypothesis generating,” the researchers wrote.
The findings were limited by several factors, including a delay in randomization from the patients’ index events, a homogeneous population, and exclusion of patients treated with prasugrel, the researchers noted. However, “based upon these findings and the unmet need for improved treatments in the postacute coronary syndromes setting, further testing of the efficacy and safety of this novel dual pathway antithrombotic regimen in an adequately powered trial should be considered,” they said.
The study was funded by Janssen Research & Development and Bayer. Lead author Dr. Ohman has received research grants from Janssen and other companies. Several coauthors disclosed relationships with multiple companies, including Janssen.
“The antithrombotic effect of aspirin is largely explained by inhibition of COX [cyclo-oxygenase] 1, a central enzyme mediating platelet activation,” wrote Paul A. Gurbel, MD, and Udaya S. Tantry, PhD, in an accompanying comment. “This and pleiotropic cardioprotective properties should be considered before forsaking or replacing aspirin, particularly early in the highly prothrombotic state of a new acute coronary syndrome (panel),” they said.
The major downside of aspirin is gastrointestinal bleeding, the commenters wrote. “But, almost all bleeding metrics were nonsignificantly lower with aspirin, and a 50% increased bleed rate with rivaroxaban cannot be excluded,” they said. Also, although the frequency of major bleeding was similar between the groups, “numerically, the lowest composite ischaemic endpoint rate was noted with aspirin plus ticagrelor therapy (ticagrelor plus aspirin = 3.9%; ticagrelor plus rivaroxaban = 4.7%; clopidogrel plus rivaroxaban = 5.4%; and clopidogrel plus aspirin = 5.9%),” they said. “Thus, it might be premature to believe that a low-dose Xa inhibitor on top of a P2Y12 inhibitor can be [an] effective and safe therapy for most stabilized patients with acute coronary syndromes” (Lancet. 2017 Mar 18. doi: org/10.1016/S0140-6736[17]30760-2).
Dr. Gurbel and Dr. Tantry are affiliated with the Inova Heart and Vascular Institute, Falls Church, VA. Dr. Gurbel disclosed relationships with multiple companies including study sponsor Janssen.
“The antithrombotic effect of aspirin is largely explained by inhibition of COX [cyclo-oxygenase] 1, a central enzyme mediating platelet activation,” wrote Paul A. Gurbel, MD, and Udaya S. Tantry, PhD, in an accompanying comment. “This and pleiotropic cardioprotective properties should be considered before forsaking or replacing aspirin, particularly early in the highly prothrombotic state of a new acute coronary syndrome (panel),” they said.
The major downside of aspirin is gastrointestinal bleeding, the commenters wrote. “But, almost all bleeding metrics were nonsignificantly lower with aspirin, and a 50% increased bleed rate with rivaroxaban cannot be excluded,” they said. Also, although the frequency of major bleeding was similar between the groups, “numerically, the lowest composite ischaemic endpoint rate was noted with aspirin plus ticagrelor therapy (ticagrelor plus aspirin = 3.9%; ticagrelor plus rivaroxaban = 4.7%; clopidogrel plus rivaroxaban = 5.4%; and clopidogrel plus aspirin = 5.9%),” they said. “Thus, it might be premature to believe that a low-dose Xa inhibitor on top of a P2Y12 inhibitor can be [an] effective and safe therapy for most stabilized patients with acute coronary syndromes” (Lancet. 2017 Mar 18. doi: org/10.1016/S0140-6736[17]30760-2).
Dr. Gurbel and Dr. Tantry are affiliated with the Inova Heart and Vascular Institute, Falls Church, VA. Dr. Gurbel disclosed relationships with multiple companies including study sponsor Janssen.
“The antithrombotic effect of aspirin is largely explained by inhibition of COX [cyclo-oxygenase] 1, a central enzyme mediating platelet activation,” wrote Paul A. Gurbel, MD, and Udaya S. Tantry, PhD, in an accompanying comment. “This and pleiotropic cardioprotective properties should be considered before forsaking or replacing aspirin, particularly early in the highly prothrombotic state of a new acute coronary syndrome (panel),” they said.
The major downside of aspirin is gastrointestinal bleeding, the commenters wrote. “But, almost all bleeding metrics were nonsignificantly lower with aspirin, and a 50% increased bleed rate with rivaroxaban cannot be excluded,” they said. Also, although the frequency of major bleeding was similar between the groups, “numerically, the lowest composite ischaemic endpoint rate was noted with aspirin plus ticagrelor therapy (ticagrelor plus aspirin = 3.9%; ticagrelor plus rivaroxaban = 4.7%; clopidogrel plus rivaroxaban = 5.4%; and clopidogrel plus aspirin = 5.9%),” they said. “Thus, it might be premature to believe that a low-dose Xa inhibitor on top of a P2Y12 inhibitor can be [an] effective and safe therapy for most stabilized patients with acute coronary syndromes” (Lancet. 2017 Mar 18. doi: org/10.1016/S0140-6736[17]30760-2).
Dr. Gurbel and Dr. Tantry are affiliated with the Inova Heart and Vascular Institute, Falls Church, VA. Dr. Gurbel disclosed relationships with multiple companies including study sponsor Janssen.
Clinically significant bleeding in acute coronary patients was approximately 5% when their P2Y12 inhibitor treatment was combined with either rivaroxaban or with aspirin, based on data from a randomized, multicenter study of 3,037 adults.
The findings support the use of low-dose rivaroxaban as a safe strategy and an alternative to aspirin for postacute care of coronary syndromes, wrote E. Magnus Ohman, MD, of Duke University in Durham, N.C., and his colleagues.
The study was presented at the annual meeting of the American College of Cardiology and published simultaneously in the Lancet (2017. Mar 18. doi: org/10.1016/S0140-6736[17]30751-1).
The GEMINI ACS 1 trial included patients older than 18 years, who were randomized to P2Y12 with rivaroxaban or P2Y12 with aspirin within 10 days of admission for acute coronary syndrome events, from 371 clinical centers in 21 countries. The patients received 2.5 mg of low-dose rivaroxaban twice daily plus a P2Y12 inhibitor (clopidogrel or ticagrelor, based on national availability) or 100 mg of aspirin daily plus a P2Y12 inhibitor. Patients were assessed at 30, 90, 180, and 270 days.
Overall, 154 patients (5%) met the primary endpoint of thrombolysis in myocardial infarction (TIMI) of clinically significant bleeding – 80 patients (5%) in the rivaroxaban group and 74 (5%) in the aspirin group. Baseline demographics were not significantly different between the groups, and clinically significant bleeding was not significantly different among subgroups.
TIMI bleeding that required medical attention was the most common, occurring in 4% of each group. Both groups had a low frequency of severe or major bleeding based on the TIMI bleeding definitions, the researchers noted.
The composite ischemic endpoint of cardiovascular death, myocardial infarction, stroke, or definite stent thrombosis was 5% in both groups, and both groups had a similar frequency of all-cause mortality and of each of the composite ischemic elements. Rivaroxaban was associated with a higher occurrence of the ischemic composite endpoint in the first 30 days (hazard ratio, 1.48), but this difference was not statistically significant.
“Additionally, no significant interaction was noted for the risk of clinically significant bleeding by P2Y12 inhibitor strata (ticagrelor vs. clopidogrel), but these stratified bleeding analyses were exploratory and hypothesis generating,” the researchers wrote.
The findings were limited by several factors, including a delay in randomization from the patients’ index events, a homogeneous population, and exclusion of patients treated with prasugrel, the researchers noted. However, “based upon these findings and the unmet need for improved treatments in the postacute coronary syndromes setting, further testing of the efficacy and safety of this novel dual pathway antithrombotic regimen in an adequately powered trial should be considered,” they said.
The study was funded by Janssen Research & Development and Bayer. Lead author Dr. Ohman has received research grants from Janssen and other companies. Several coauthors disclosed relationships with multiple companies, including Janssen.
Clinically significant bleeding in acute coronary patients was approximately 5% when their P2Y12 inhibitor treatment was combined with either rivaroxaban or with aspirin, based on data from a randomized, multicenter study of 3,037 adults.
The findings support the use of low-dose rivaroxaban as a safe strategy and an alternative to aspirin for postacute care of coronary syndromes, wrote E. Magnus Ohman, MD, of Duke University in Durham, N.C., and his colleagues.
The study was presented at the annual meeting of the American College of Cardiology and published simultaneously in the Lancet (2017. Mar 18. doi: org/10.1016/S0140-6736[17]30751-1).
The GEMINI ACS 1 trial included patients older than 18 years, who were randomized to P2Y12 with rivaroxaban or P2Y12 with aspirin within 10 days of admission for acute coronary syndrome events, from 371 clinical centers in 21 countries. The patients received 2.5 mg of low-dose rivaroxaban twice daily plus a P2Y12 inhibitor (clopidogrel or ticagrelor, based on national availability) or 100 mg of aspirin daily plus a P2Y12 inhibitor. Patients were assessed at 30, 90, 180, and 270 days.
Overall, 154 patients (5%) met the primary endpoint of thrombolysis in myocardial infarction (TIMI) of clinically significant bleeding – 80 patients (5%) in the rivaroxaban group and 74 (5%) in the aspirin group. Baseline demographics were not significantly different between the groups, and clinically significant bleeding was not significantly different among subgroups.
TIMI bleeding that required medical attention was the most common, occurring in 4% of each group. Both groups had a low frequency of severe or major bleeding based on the TIMI bleeding definitions, the researchers noted.
The composite ischemic endpoint of cardiovascular death, myocardial infarction, stroke, or definite stent thrombosis was 5% in both groups, and both groups had a similar frequency of all-cause mortality and of each of the composite ischemic elements. Rivaroxaban was associated with a higher occurrence of the ischemic composite endpoint in the first 30 days (hazard ratio, 1.48), but this difference was not statistically significant.
“Additionally, no significant interaction was noted for the risk of clinically significant bleeding by P2Y12 inhibitor strata (ticagrelor vs. clopidogrel), but these stratified bleeding analyses were exploratory and hypothesis generating,” the researchers wrote.
The findings were limited by several factors, including a delay in randomization from the patients’ index events, a homogeneous population, and exclusion of patients treated with prasugrel, the researchers noted. However, “based upon these findings and the unmet need for improved treatments in the postacute coronary syndromes setting, further testing of the efficacy and safety of this novel dual pathway antithrombotic regimen in an adequately powered trial should be considered,” they said.
The study was funded by Janssen Research & Development and Bayer. Lead author Dr. Ohman has received research grants from Janssen and other companies. Several coauthors disclosed relationships with multiple companies, including Janssen.
FROM ACC 17
Key clinical point: The risk of major bleeding was similar between acute coronary syndrome patients treated with a combination of low-dose rivaroxaban and P2Y12 inhibitor and those treated with aspirin and P2Y12 inhibitor.
Major finding: Clinically significant bleeding occurred in 5% of patients in each treatment group (HR, 1.09).
Data source: A double-blind, multicenter, randomized trial (GEMINI ACS 1) including 3,037 adults.
Disclosures: The study was funded by Janssen Research & Development and Bayer. Lead author Dr. Ohman has received research grants from Janssen and other companies. Several coauthors disclosed relationships with multiple companies, including Janssen.
A little rivaroxaban goes a long way
In patients with venous thromboembolism at equipoise for further anticoagulation therapy, treatment with a 10-mg dose of rivaroxaban (Xarelto) had comparable efficacy to a 20-mg dose, with both leading to fewer recurrences than treatment with aspirin. There were no statistically significant differences in clinically relevant nonmajor bleeding between the three groups.
The study’s conclusions are limited to relatively healthy patients such as the ones who were selected for the study.
The findings were presented at the annual meeting of the American College of Cardiology and published simultaneously in the New England Journal of Medicine (N Engl J Med 2017 March 18. doi: 10.1056/NEJMoa1700518).
Anticoagulants are the primary treatment for prevention of venous thromboembolism recurrences, but the medications are often stopped after 6-12 months because of concerns about bleeding. To counter that issue, physicians may prescribe lower doses of anticoagulants such as rivaroxaban, or substitute aspirin.
The work follows another recent study of apixaban (Eliquis), which showed that a 2.5-mg twice-daily dose performed the same as did a 5.0-mg twice-daily dose in the prevention of venous thromboembolism recurrence (N Engl J Med. 2013;368[8]:699-708).
“I think the story is kind of the same here,” said David Garcia, MD, professor of hematology at the University of Washington, Seattle, who was one of the principal investigators in the trial.
Patients with unprompted venous thromboembolism are increasingly being offered anticoagulant therapy to prevent recurrences. Those drugs have inherent bleeding risks, but the newer drugs and even warfarin are becoming safer. Even so, “as we embark on that, one has to remember that the risk of anticoagulants is cumulative. It may only carry a risk of 1% per year of major hemorrhage, but if the patient has to take it for 10 or 20 or 30 years, it’s a nontrivial risk of major bleeding over that time,” said Dr. Garcia.
The researchers conducted the Reduced-Dose Rivaroxaban in the Long-Term Prevention of Recurrent Symptomatic Venous Thromboembolism (EINSTEIN CHOICE) trial, in which 3,365 patients from 24 sites were randomized to receive 20 mg rivaroxaban, 10 mg rivaroxaban, or 100 mg aspirin for up to 1 year following an initial 6-12 months of treatment with anticoagulation therapy.
During a median follow-up of 1 year, 4.4% of patients on aspirin experienced a recurrence, compared with 1.5% of patients in the 20-mg rivaroxaban group (hazard ratio versus aspirin, 0.34; 95% confidence interval, 0.20-0.59; P less than .001), and 1.2% in the 10-mg rivaroxaban group (HR versus aspirin, 0.26; 95% CI, 0.14-0.47; P less than .001). There was no statistical significance between the two doses of rivaroxaban.
The rates of fatal thromboembolism were similar, at 0.2% in the 20-mg rivaroxaban group, 0% in the 10-mg group, and 0.2% in the aspirin group.
Major bleeding occurred in 0.5% of patients in the 20-mg rivaroxaban group, in 0.4% of the 10-mg rivaroxaban group, and 0.3% in the aspirin group. Nonmajor, clinically relevant bleeding was also similar between groups, at 2.7% in the 20-mg group, 2.0% in the 10-mg group, and 1.8% in the aspirin group. These differences were not statistically significant.
The study is good news for clinicians as they help patients decide whether to undergo preventive therapy. “Even before the newer agents arrived on the market, we had moved the needle a lot in terms of maximizing the safety of warfarin. I think these drugs take it to yet another level,” said Dr. Garcia.
Bayer Pharmaceuticals funded the study. Dr. Garcia has received honoraria from Bristol-Meyers Squibb, Pfizer, and Boehringer Ingelheim.
“Given the protection from recurrent venous thromboembolism afforded by reduced-dose rivaroxaban, extending treatment beyond 3 months could be considered in patients with provoked venous thromboembolism who are at average risk for bleeding and who are strongly averse to having another episode of venous thromboembolism. In light of the safety profile of low-dose rivaroxaban, the benefit of this strategy does not need to be large in order to justify the extension of therapy.
“This trial suggests that it would be helpful to evaluate the effects of reduced doses of rivaroxaban within 6 months after an episode of venous thromboembolism.
“For patients without cancer, the use of direct oral anticoagulant agents might be considered as first-line treatment for those with acute venous thromboembolism. Full-dose treatment could be continued for a minimum of 3-6 months. In patients in whom there is equipoise with respect to continuing anticoagulant therapy beyond this period, the use of a reduced-intensity direct oral anticoagulant agent might be considered. Clinicians who choose this strategy can be confident of excellent efficacy and low bleeding risk similar to that observed with aspirin or placebo” (N Engl J Med 2017 March 18. doi: 10.1056/NEJMe1701628).
Mark Crowther, MD, is professor of medicine at McMaster University, Hamilton, Ont. Adam Cuker is assistant professor of medicine at the hospital of the University of Pennsylvania, Philadelphia.
“Given the protection from recurrent venous thromboembolism afforded by reduced-dose rivaroxaban, extending treatment beyond 3 months could be considered in patients with provoked venous thromboembolism who are at average risk for bleeding and who are strongly averse to having another episode of venous thromboembolism. In light of the safety profile of low-dose rivaroxaban, the benefit of this strategy does not need to be large in order to justify the extension of therapy.
“This trial suggests that it would be helpful to evaluate the effects of reduced doses of rivaroxaban within 6 months after an episode of venous thromboembolism.
“For patients without cancer, the use of direct oral anticoagulant agents might be considered as first-line treatment for those with acute venous thromboembolism. Full-dose treatment could be continued for a minimum of 3-6 months. In patients in whom there is equipoise with respect to continuing anticoagulant therapy beyond this period, the use of a reduced-intensity direct oral anticoagulant agent might be considered. Clinicians who choose this strategy can be confident of excellent efficacy and low bleeding risk similar to that observed with aspirin or placebo” (N Engl J Med 2017 March 18. doi: 10.1056/NEJMe1701628).
Mark Crowther, MD, is professor of medicine at McMaster University, Hamilton, Ont. Adam Cuker is assistant professor of medicine at the hospital of the University of Pennsylvania, Philadelphia.
“Given the protection from recurrent venous thromboembolism afforded by reduced-dose rivaroxaban, extending treatment beyond 3 months could be considered in patients with provoked venous thromboembolism who are at average risk for bleeding and who are strongly averse to having another episode of venous thromboembolism. In light of the safety profile of low-dose rivaroxaban, the benefit of this strategy does not need to be large in order to justify the extension of therapy.
“This trial suggests that it would be helpful to evaluate the effects of reduced doses of rivaroxaban within 6 months after an episode of venous thromboembolism.
“For patients without cancer, the use of direct oral anticoagulant agents might be considered as first-line treatment for those with acute venous thromboembolism. Full-dose treatment could be continued for a minimum of 3-6 months. In patients in whom there is equipoise with respect to continuing anticoagulant therapy beyond this period, the use of a reduced-intensity direct oral anticoagulant agent might be considered. Clinicians who choose this strategy can be confident of excellent efficacy and low bleeding risk similar to that observed with aspirin or placebo” (N Engl J Med 2017 March 18. doi: 10.1056/NEJMe1701628).
Mark Crowther, MD, is professor of medicine at McMaster University, Hamilton, Ont. Adam Cuker is assistant professor of medicine at the hospital of the University of Pennsylvania, Philadelphia.
In patients with venous thromboembolism at equipoise for further anticoagulation therapy, treatment with a 10-mg dose of rivaroxaban (Xarelto) had comparable efficacy to a 20-mg dose, with both leading to fewer recurrences than treatment with aspirin. There were no statistically significant differences in clinically relevant nonmajor bleeding between the three groups.
The study’s conclusions are limited to relatively healthy patients such as the ones who were selected for the study.
The findings were presented at the annual meeting of the American College of Cardiology and published simultaneously in the New England Journal of Medicine (N Engl J Med 2017 March 18. doi: 10.1056/NEJMoa1700518).
Anticoagulants are the primary treatment for prevention of venous thromboembolism recurrences, but the medications are often stopped after 6-12 months because of concerns about bleeding. To counter that issue, physicians may prescribe lower doses of anticoagulants such as rivaroxaban, or substitute aspirin.
The work follows another recent study of apixaban (Eliquis), which showed that a 2.5-mg twice-daily dose performed the same as did a 5.0-mg twice-daily dose in the prevention of venous thromboembolism recurrence (N Engl J Med. 2013;368[8]:699-708).
“I think the story is kind of the same here,” said David Garcia, MD, professor of hematology at the University of Washington, Seattle, who was one of the principal investigators in the trial.
Patients with unprompted venous thromboembolism are increasingly being offered anticoagulant therapy to prevent recurrences. Those drugs have inherent bleeding risks, but the newer drugs and even warfarin are becoming safer. Even so, “as we embark on that, one has to remember that the risk of anticoagulants is cumulative. It may only carry a risk of 1% per year of major hemorrhage, but if the patient has to take it for 10 or 20 or 30 years, it’s a nontrivial risk of major bleeding over that time,” said Dr. Garcia.
The researchers conducted the Reduced-Dose Rivaroxaban in the Long-Term Prevention of Recurrent Symptomatic Venous Thromboembolism (EINSTEIN CHOICE) trial, in which 3,365 patients from 24 sites were randomized to receive 20 mg rivaroxaban, 10 mg rivaroxaban, or 100 mg aspirin for up to 1 year following an initial 6-12 months of treatment with anticoagulation therapy.
During a median follow-up of 1 year, 4.4% of patients on aspirin experienced a recurrence, compared with 1.5% of patients in the 20-mg rivaroxaban group (hazard ratio versus aspirin, 0.34; 95% confidence interval, 0.20-0.59; P less than .001), and 1.2% in the 10-mg rivaroxaban group (HR versus aspirin, 0.26; 95% CI, 0.14-0.47; P less than .001). There was no statistical significance between the two doses of rivaroxaban.
The rates of fatal thromboembolism were similar, at 0.2% in the 20-mg rivaroxaban group, 0% in the 10-mg group, and 0.2% in the aspirin group.
Major bleeding occurred in 0.5% of patients in the 20-mg rivaroxaban group, in 0.4% of the 10-mg rivaroxaban group, and 0.3% in the aspirin group. Nonmajor, clinically relevant bleeding was also similar between groups, at 2.7% in the 20-mg group, 2.0% in the 10-mg group, and 1.8% in the aspirin group. These differences were not statistically significant.
The study is good news for clinicians as they help patients decide whether to undergo preventive therapy. “Even before the newer agents arrived on the market, we had moved the needle a lot in terms of maximizing the safety of warfarin. I think these drugs take it to yet another level,” said Dr. Garcia.
Bayer Pharmaceuticals funded the study. Dr. Garcia has received honoraria from Bristol-Meyers Squibb, Pfizer, and Boehringer Ingelheim.
In patients with venous thromboembolism at equipoise for further anticoagulation therapy, treatment with a 10-mg dose of rivaroxaban (Xarelto) had comparable efficacy to a 20-mg dose, with both leading to fewer recurrences than treatment with aspirin. There were no statistically significant differences in clinically relevant nonmajor bleeding between the three groups.
The study’s conclusions are limited to relatively healthy patients such as the ones who were selected for the study.
The findings were presented at the annual meeting of the American College of Cardiology and published simultaneously in the New England Journal of Medicine (N Engl J Med 2017 March 18. doi: 10.1056/NEJMoa1700518).
Anticoagulants are the primary treatment for prevention of venous thromboembolism recurrences, but the medications are often stopped after 6-12 months because of concerns about bleeding. To counter that issue, physicians may prescribe lower doses of anticoagulants such as rivaroxaban, or substitute aspirin.
The work follows another recent study of apixaban (Eliquis), which showed that a 2.5-mg twice-daily dose performed the same as did a 5.0-mg twice-daily dose in the prevention of venous thromboembolism recurrence (N Engl J Med. 2013;368[8]:699-708).
“I think the story is kind of the same here,” said David Garcia, MD, professor of hematology at the University of Washington, Seattle, who was one of the principal investigators in the trial.
Patients with unprompted venous thromboembolism are increasingly being offered anticoagulant therapy to prevent recurrences. Those drugs have inherent bleeding risks, but the newer drugs and even warfarin are becoming safer. Even so, “as we embark on that, one has to remember that the risk of anticoagulants is cumulative. It may only carry a risk of 1% per year of major hemorrhage, but if the patient has to take it for 10 or 20 or 30 years, it’s a nontrivial risk of major bleeding over that time,” said Dr. Garcia.
The researchers conducted the Reduced-Dose Rivaroxaban in the Long-Term Prevention of Recurrent Symptomatic Venous Thromboembolism (EINSTEIN CHOICE) trial, in which 3,365 patients from 24 sites were randomized to receive 20 mg rivaroxaban, 10 mg rivaroxaban, or 100 mg aspirin for up to 1 year following an initial 6-12 months of treatment with anticoagulation therapy.
During a median follow-up of 1 year, 4.4% of patients on aspirin experienced a recurrence, compared with 1.5% of patients in the 20-mg rivaroxaban group (hazard ratio versus aspirin, 0.34; 95% confidence interval, 0.20-0.59; P less than .001), and 1.2% in the 10-mg rivaroxaban group (HR versus aspirin, 0.26; 95% CI, 0.14-0.47; P less than .001). There was no statistical significance between the two doses of rivaroxaban.
The rates of fatal thromboembolism were similar, at 0.2% in the 20-mg rivaroxaban group, 0% in the 10-mg group, and 0.2% in the aspirin group.
Major bleeding occurred in 0.5% of patients in the 20-mg rivaroxaban group, in 0.4% of the 10-mg rivaroxaban group, and 0.3% in the aspirin group. Nonmajor, clinically relevant bleeding was also similar between groups, at 2.7% in the 20-mg group, 2.0% in the 10-mg group, and 1.8% in the aspirin group. These differences were not statistically significant.
The study is good news for clinicians as they help patients decide whether to undergo preventive therapy. “Even before the newer agents arrived on the market, we had moved the needle a lot in terms of maximizing the safety of warfarin. I think these drugs take it to yet another level,” said Dr. Garcia.
Bayer Pharmaceuticals funded the study. Dr. Garcia has received honoraria from Bristol-Meyers Squibb, Pfizer, and Boehringer Ingelheim.
FROM ACC 17
Key clinical point: In venous thromboembolism prevention, a 10-mg dose matched 20 mg.
Major finding: The recurrence rates were 1.2% at 10 mg versus 4.4% with aspirin.
Data source: Randomized comparison trial of 3,365 patients.
Disclosures: Bayer Pharmaceuticals funded the study. Dr. Garcia has received honoraria from Bristol-Meyers Squibb, Pfizer, and Boehringer Ingelheim.
VIDEO: SURTAVI results ‘tremendously important’ for decision making
Washington – Heart teams will have more options when making treatment decisions for patients with severe aortic stenosis who are at intermediate risk, now that the results of the SURTAVI (Surgical Replacement and Transcatheter Aortic Valve Implantation) trial have been presented.
Those results showed that transcatheter aortic valve replacement (TAVR) in patients with severe aortic stenosis at intermediate risk was not only noninferior to surgical replacement, “but in my mind superior, because you don’t get your chest cracked, you get home earlier, and you have fewer strokes [in this trial], Roxana Mehran, MD, professor and director of interventional cardiovascular research at Mount Sinai Hospital in New York, said in a video interview at the annual meeting of the American College of Cardiology.
In SURTAVI, which used Medtronic’s self-expanding CoreValve and Evolut-R bioprostheses in 863 patients randomized to TAVR, 12.6% met the study’s primary endpoint – death from any cause or disabling stroke at 24 months – versus 14% of the 796 patients randomized to surgery, a statistically nonsignificant difference. Notably, the risk of any type of stroke at 30 days was statistically superior for TAVR, 3.4%, compared with 5.6% for surgical replacement.
“It’s tremendously important to see the change in how we’re going to be evaluating patients with aortic stenosis,” Dr. Mehran said.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
Washington – Heart teams will have more options when making treatment decisions for patients with severe aortic stenosis who are at intermediate risk, now that the results of the SURTAVI (Surgical Replacement and Transcatheter Aortic Valve Implantation) trial have been presented.
Those results showed that transcatheter aortic valve replacement (TAVR) in patients with severe aortic stenosis at intermediate risk was not only noninferior to surgical replacement, “but in my mind superior, because you don’t get your chest cracked, you get home earlier, and you have fewer strokes [in this trial], Roxana Mehran, MD, professor and director of interventional cardiovascular research at Mount Sinai Hospital in New York, said in a video interview at the annual meeting of the American College of Cardiology.
In SURTAVI, which used Medtronic’s self-expanding CoreValve and Evolut-R bioprostheses in 863 patients randomized to TAVR, 12.6% met the study’s primary endpoint – death from any cause or disabling stroke at 24 months – versus 14% of the 796 patients randomized to surgery, a statistically nonsignificant difference. Notably, the risk of any type of stroke at 30 days was statistically superior for TAVR, 3.4%, compared with 5.6% for surgical replacement.
“It’s tremendously important to see the change in how we’re going to be evaluating patients with aortic stenosis,” Dr. Mehran said.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
Washington – Heart teams will have more options when making treatment decisions for patients with severe aortic stenosis who are at intermediate risk, now that the results of the SURTAVI (Surgical Replacement and Transcatheter Aortic Valve Implantation) trial have been presented.
Those results showed that transcatheter aortic valve replacement (TAVR) in patients with severe aortic stenosis at intermediate risk was not only noninferior to surgical replacement, “but in my mind superior, because you don’t get your chest cracked, you get home earlier, and you have fewer strokes [in this trial], Roxana Mehran, MD, professor and director of interventional cardiovascular research at Mount Sinai Hospital in New York, said in a video interview at the annual meeting of the American College of Cardiology.
In SURTAVI, which used Medtronic’s self-expanding CoreValve and Evolut-R bioprostheses in 863 patients randomized to TAVR, 12.6% met the study’s primary endpoint – death from any cause or disabling stroke at 24 months – versus 14% of the 796 patients randomized to surgery, a statistically nonsignificant difference. Notably, the risk of any type of stroke at 30 days was statistically superior for TAVR, 3.4%, compared with 5.6% for surgical replacement.
“It’s tremendously important to see the change in how we’re going to be evaluating patients with aortic stenosis,” Dr. Mehran said.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
AT ACC 17
