ACC 2015

SAN DIEGO – Patients with new-onset, stable chest pain account for millions of stress tests annually in the United States, but randomized data are limited on which test is best and the impact of testing on clinical outcomes.

Results from the prospective PROMISE trial, presented at the annual meeting of the American College of Cardiology, show there is no Holy Grail testing strategy. First-line testing with CT angiography did not reduce hard clinical events compared with functional testing, but did cut the number of patients undergoing an invasive catheterization showing no obstructive coronary artery disease.

Listen here for our interview with ACC president Dr. Patrick O’Gara on how these results will impact patient care and potentially influence current guideline recommendations.

Dr. O’Gara reported no relevant financial conflicts.

pwendling@frontlinemedcom.com

SAN DIEGO – Patients with new-onset, stable chest pain account for millions of stress tests annually in the United States, but randomized data are limited on which test is best and the impact of testing on clinical outcomes.

Results from the prospective PROMISE trial, presented at the annual meeting of the American College of Cardiology, show there is no Holy Grail testing strategy. First-line testing with CT angiography did not reduce hard clinical events compared with functional testing, but did cut the number of patients undergoing an invasive catheterization showing no obstructive coronary artery disease.

Listen here for our interview with ACC president Dr. Patrick O’Gara on how these results will impact patient care and potentially influence current guideline recommendations.

Dr. O’Gara reported no relevant financial conflicts.

pwendling@frontlinemedcom.com

SAN DIEGO – Patients with new-onset, stable chest pain account for millions of stress tests annually in the United States, but randomized data are limited on which test is best and the impact of testing on clinical outcomes.

Results from the prospective PROMISE trial, presented at the annual meeting of the American College of Cardiology, show there is no Holy Grail testing strategy. First-line testing with CT angiography did not reduce hard clinical events compared with functional testing, but did cut the number of patients undergoing an invasive catheterization showing no obstructive coronary artery disease.

Listen here for our interview with ACC president Dr. Patrick O’Gara on how these results will impact patient care and potentially influence current guideline recommendations.

Dr. O’Gara reported no relevant financial conflicts.

pwendling@frontlinemedcom.com

SAN DIEGO– Percutaneous coronary intervention with everolimus-eluting stents is associated with significantly higher major adverse cardiovascular events than is coronary artery bypass grafting in patients with multivessel coronary artery disease, according to results of the BEST trial.

In the randomized noninferiority trial of 880 patients, there was a 47% higher rate of the primary endpoint of death, myocardial infarction, or target vessel revascularization among patients randomized to percutaneous coronary intervention (PCI) with the new-generation drug-eluting stent than among those randomized to coronary artery bypass grafting (CABG), after a median of 4.6 years follow-up.

However, the differences in primary endpoint were not significant for noninferiority between the two groups at the 2-year follow-up mark, Dr. Seung-Jung Park said at the annual meeting of the American College of Cardiology.

The Xience everolimus-eluting stent used in BEST (Randomized Comparison of Coronary Artery Bypass Surgery and Everolimus-Eluting Stent Implantation in the Treatment of Patients with Multivessel Coronary Artery Disease) is one of several bioabsorbable vascular scaffolds that have caught on in recent years. The working hypothesis behind the device is that by dissolving during a period of 12-24 months, the scaffold provides temporary bracing against restenosis but then disappears, allowing improved endovascular healing.

Patients were randomized after diagnostic coronary angiography to PCI (438 patients) or to CABG (442).

The study, which was terminated early because of slow enrollment, also found a significantly greater rate of the composite secondary endpoint of death, myocardial infarction, stroke, or repeat revascularization in the PCI group compared to the CABG group (19.9% vs. 13.3%, P = .01).

There were no significant differences between the two groups in the rate of the other secondary safety endpoint: a composite of death, MI, and stroke.

In total, 29 patients assigned to PCI died, compared with 22 assigned to CABG (6.6% vs. 5%, P = .30).

The rate of spontaneous myocardial infarction was significantly higher in the PCI group (4.3% vs. 1.6%, P = .02), as was the rate of repeat revascularization (11% vs. 5.4%, P = .003).

There were fewer incidences of major bleeding in the PCI group compared to the CABG group, although the rate of fatal major bleeding was similar for both arms of the study.

Diabetes status had a major negative impact on outcome for patients undergoing PCI, increasing the rate of the primary endpoint to 19.2%, compared to 9.1% in patients undergoing CABG (P = .007).

“In the BEST trial, PCI with everolimus-eluting stents was not shown to be noninferior to CABG with respect to the primary endpoint of death, myocardial infarction, or target vessel revascularization at 2 years,” wrote Dr. Park of the University of Ulsan College of Medicine, and his coauthors. The article was published online simultaneously with his presentation (N. Engl. J. Med. 2015 March 15 [doi:10.1056/NEJMoa1415447]).

“At longer-term follow-up (median 4.6 years), PCI was associated with a significant increase in the incidence of the primary endpoint, as compared to the incidence with CABG.”

The authors suggested this difference was largely attributable to the higher rate of repeat target-vessel revascularization in patients who had undergone PCI, as well as the spontaneous myocardial infarction and new lesion revascularization.

In contrast to previous studies, the researchers did not find a significant difference in the rate of stroke between the two groups.

“The reason for this discrepancy is not clear, but the use of off-pump CABG can avoid excessive manipulation of the aorta, and may have contributed to a reduced rate of stroke in the CABG group in our study,” the authors noted.

The researchers acknowledged that the trial was not powered to detect differences in individual endpoints and that they did experience enrollment difficulties.

The CardioVascular Research Foundation, Abbott Vascular, and the Korea Healthcare Technology Research and Development Project supported the study. Dr. Park disclosed ties with Abbott, Cordis, Boston Scientific, and Medtronic, and has an ownership interest in the Cardiovascular Research Foundation.

SAN DIEGO– Percutaneous coronary intervention with everolimus-eluting stents is associated with significantly higher major adverse cardiovascular events than is coronary artery bypass grafting in patients with multivessel coronary artery disease, according to results of the BEST trial.

In the randomized noninferiority trial of 880 patients, there was a 47% higher rate of the primary endpoint of death, myocardial infarction, or target vessel revascularization among patients randomized to percutaneous coronary intervention (PCI) with the new-generation drug-eluting stent than among those randomized to coronary artery bypass grafting (CABG), after a median of 4.6 years follow-up.

However, the differences in primary endpoint were not significant for noninferiority between the two groups at the 2-year follow-up mark, Dr. Seung-Jung Park said at the annual meeting of the American College of Cardiology.

The Xience everolimus-eluting stent used in BEST (Randomized Comparison of Coronary Artery Bypass Surgery and Everolimus-Eluting Stent Implantation in the Treatment of Patients with Multivessel Coronary Artery Disease) is one of several bioabsorbable vascular scaffolds that have caught on in recent years. The working hypothesis behind the device is that by dissolving during a period of 12-24 months, the scaffold provides temporary bracing against restenosis but then disappears, allowing improved endovascular healing.

Patients were randomized after diagnostic coronary angiography to PCI (438 patients) or to CABG (442).

The study, which was terminated early because of slow enrollment, also found a significantly greater rate of the composite secondary endpoint of death, myocardial infarction, stroke, or repeat revascularization in the PCI group compared to the CABG group (19.9% vs. 13.3%, P = .01).

There were no significant differences between the two groups in the rate of the other secondary safety endpoint: a composite of death, MI, and stroke.

In total, 29 patients assigned to PCI died, compared with 22 assigned to CABG (6.6% vs. 5%, P = .30).

The rate of spontaneous myocardial infarction was significantly higher in the PCI group (4.3% vs. 1.6%, P = .02), as was the rate of repeat revascularization (11% vs. 5.4%, P = .003).

There were fewer incidences of major bleeding in the PCI group compared to the CABG group, although the rate of fatal major bleeding was similar for both arms of the study.

Diabetes status had a major negative impact on outcome for patients undergoing PCI, increasing the rate of the primary endpoint to 19.2%, compared to 9.1% in patients undergoing CABG (P = .007).

“In the BEST trial, PCI with everolimus-eluting stents was not shown to be noninferior to CABG with respect to the primary endpoint of death, myocardial infarction, or target vessel revascularization at 2 years,” wrote Dr. Park of the University of Ulsan College of Medicine, and his coauthors. The article was published online simultaneously with his presentation (N. Engl. J. Med. 2015 March 15 [doi:10.1056/NEJMoa1415447]).

“At longer-term follow-up (median 4.6 years), PCI was associated with a significant increase in the incidence of the primary endpoint, as compared to the incidence with CABG.”

The authors suggested this difference was largely attributable to the higher rate of repeat target-vessel revascularization in patients who had undergone PCI, as well as the spontaneous myocardial infarction and new lesion revascularization.

In contrast to previous studies, the researchers did not find a significant difference in the rate of stroke between the two groups.

“The reason for this discrepancy is not clear, but the use of off-pump CABG can avoid excessive manipulation of the aorta, and may have contributed to a reduced rate of stroke in the CABG group in our study,” the authors noted.

The researchers acknowledged that the trial was not powered to detect differences in individual endpoints and that they did experience enrollment difficulties.

The CardioVascular Research Foundation, Abbott Vascular, and the Korea Healthcare Technology Research and Development Project supported the study. Dr. Park disclosed ties with Abbott, Cordis, Boston Scientific, and Medtronic, and has an ownership interest in the Cardiovascular Research Foundation.

SAN DIEGO– Percutaneous coronary intervention with everolimus-eluting stents is associated with significantly higher major adverse cardiovascular events than is coronary artery bypass grafting in patients with multivessel coronary artery disease, according to results of the BEST trial.

In the randomized noninferiority trial of 880 patients, there was a 47% higher rate of the primary endpoint of death, myocardial infarction, or target vessel revascularization among patients randomized to percutaneous coronary intervention (PCI) with the new-generation drug-eluting stent than among those randomized to coronary artery bypass grafting (CABG), after a median of 4.6 years follow-up.

However, the differences in primary endpoint were not significant for noninferiority between the two groups at the 2-year follow-up mark, Dr. Seung-Jung Park said at the annual meeting of the American College of Cardiology.

The Xience everolimus-eluting stent used in BEST (Randomized Comparison of Coronary Artery Bypass Surgery and Everolimus-Eluting Stent Implantation in the Treatment of Patients with Multivessel Coronary Artery Disease) is one of several bioabsorbable vascular scaffolds that have caught on in recent years. The working hypothesis behind the device is that by dissolving during a period of 12-24 months, the scaffold provides temporary bracing against restenosis but then disappears, allowing improved endovascular healing.

Patients were randomized after diagnostic coronary angiography to PCI (438 patients) or to CABG (442).

The study, which was terminated early because of slow enrollment, also found a significantly greater rate of the composite secondary endpoint of death, myocardial infarction, stroke, or repeat revascularization in the PCI group compared to the CABG group (19.9% vs. 13.3%, P = .01).

There were no significant differences between the two groups in the rate of the other secondary safety endpoint: a composite of death, MI, and stroke.

In total, 29 patients assigned to PCI died, compared with 22 assigned to CABG (6.6% vs. 5%, P = .30).

The rate of spontaneous myocardial infarction was significantly higher in the PCI group (4.3% vs. 1.6%, P = .02), as was the rate of repeat revascularization (11% vs. 5.4%, P = .003).

There were fewer incidences of major bleeding in the PCI group compared to the CABG group, although the rate of fatal major bleeding was similar for both arms of the study.

Diabetes status had a major negative impact on outcome for patients undergoing PCI, increasing the rate of the primary endpoint to 19.2%, compared to 9.1% in patients undergoing CABG (P = .007).

“In the BEST trial, PCI with everolimus-eluting stents was not shown to be noninferior to CABG with respect to the primary endpoint of death, myocardial infarction, or target vessel revascularization at 2 years,” wrote Dr. Park of the University of Ulsan College of Medicine, and his coauthors. The article was published online simultaneously with his presentation (N. Engl. J. Med. 2015 March 15 [doi:10.1056/NEJMoa1415447]).

“At longer-term follow-up (median 4.6 years), PCI was associated with a significant increase in the incidence of the primary endpoint, as compared to the incidence with CABG.”

The authors suggested this difference was largely attributable to the higher rate of repeat target-vessel revascularization in patients who had undergone PCI, as well as the spontaneous myocardial infarction and new lesion revascularization.

In contrast to previous studies, the researchers did not find a significant difference in the rate of stroke between the two groups.

“The reason for this discrepancy is not clear, but the use of off-pump CABG can avoid excessive manipulation of the aorta, and may have contributed to a reduced rate of stroke in the CABG group in our study,” the authors noted.

The researchers acknowledged that the trial was not powered to detect differences in individual endpoints and that they did experience enrollment difficulties.

The CardioVascular Research Foundation, Abbott Vascular, and the Korea Healthcare Technology Research and Development Project supported the study. Dr. Park disclosed ties with Abbott, Cordis, Boston Scientific, and Medtronic, and has an ownership interest in the Cardiovascular Research Foundation.

SAN DIEGO – The addition of CT angiography to standard care changed the diagnosis and treatment of one in four patients with stable chest pain in the prospective, randomized SCOT-HEART trial.

CT angiography (CTA) also reduced coronary heart disease deaths or myocardial infarctions by 38% after a median follow-up of 1.7 years, although the finding was of borderline significance (hazard ratio, 0.62; P = .053).

A post-hoc, landmark analysis, however, that accounted for the roughly 6-week delay between the clinic visit and implementation or alteration of therapy based on CTA findings, showed a halving of these outcomes (HR, 0.50; P = .015), chief investigator Dr. David Newby reported at the annual meeting of the American College of Cardiology.

SCOT-HEART (Scottish COmputed Tomography of the Heart trial) involved 4,146 patients referred from chest pain clinics across Scotland for assessment of suspected angina due to coronary artery disease, of whom 47% were diagnosed in the clinic with coronary heart disease and 36% with angina due to coronary heart disease. Patients were then evenly randomized to standard care involving cardiovascular risk assessment with the ASSIGN Score alone or with CTA.

When attending clinicians reviewed the cases at 6 weeks, the diagnosis of coronary heart disease (CHD) changed in 25% of patients assigned CTA vs. only 1% assigned standard care alone and the diagnosis of angina due to CHD changed in 23% vs. 1% (P value < .001 for both), Dr. Newby, from the University of Edinburgh, said.

Clinicians reported that CTA significantly increased the certainty (Relative risk, 2.56; P < .0001) and frequency (RR, 1.09; P = .017) of the diagnosis of CHD and increased the certainty of a diagnosis of angina due to CHD (RR, 1.79; P < .0001), but had no effect on its frequency (RR, 0.93; P = .12).

Overall, 63% of patients had evidence of CHD on CTA, with 25% having obstructive disease.

CTA altered subsequent testing in 15% of patients vs. only 1% with standard care (P < .001). CTA use was associated with the cancellation of 121 functional stress tests and 29 invasive coronary angiography exams. CTA also prompted 94 new angiograms vs. just 8 with standard care, but this was mainly the result of the exclusion or discovery of obstructive coronary heart disease, including triple vessel disease, Dr. Newby observed. CT was associated with a nonsignificant increase in coronary revascularizations (11.2% vs. 9.7%; HR, 1.19; P .06).

The changes in diagnosis and testing were associated with changes in subsequent treatment in 23% of CTA patients vs. 5% of standard care patients overall (P < .001), including recommendations and cancellations for preventive and anti-anginal therapies. The results were also simultaneously published online (Lancet 2015 [doi:10.19016/S0140-6736(15)060291-4]).

The most impressive aspect of SCOT-HEART was the strong trend for improved outcomes in patients for which therapeutic alterations were made, Dr. Eric Peterson, with the Duke University in Durham, N.C., commented.

“This sets the standard for how we perform and evaluate whether CT can improve outcomes for patients,” he said.

In an editorial accompanying the report,, Dr. Pamela Douglas, from the Duke Clinical Research Institute in Durham, N.C., called the finding of reduced death and MI “intriguing,” but urged caution in its interpretation because it was one of 22 secondary end points and the absolute difference between groups was only 16 events (Lancet 2015; [doi: 10.1016/S0140-6736(15)60463-9]). Earlier in the meeting, she reported that the PROMISE trial found no difference in its primary composite end point of all-cause death, nonfatal myocardial infarction, unstable angina hospitalization, and major cardiovascular procedural complications among chest pain patients evaluated with CTA or functional testing.

Finally, it was noted that radiation exposure in SCOT-HEART (median 4.1 mSv) was substantially lower than that reported in PROMISE, a finding Dr. Newby said he could not explain.

pwendling@frontlinemedcom.com

SAN DIEGO – The addition of CT angiography to standard care changed the diagnosis and treatment of one in four patients with stable chest pain in the prospective, randomized SCOT-HEART trial.

CT angiography (CTA) also reduced coronary heart disease deaths or myocardial infarctions by 38% after a median follow-up of 1.7 years, although the finding was of borderline significance (hazard ratio, 0.62; P = .053).

A post-hoc, landmark analysis, however, that accounted for the roughly 6-week delay between the clinic visit and implementation or alteration of therapy based on CTA findings, showed a halving of these outcomes (HR, 0.50; P = .015), chief investigator Dr. David Newby reported at the annual meeting of the American College of Cardiology.

SCOT-HEART (Scottish COmputed Tomography of the Heart trial) involved 4,146 patients referred from chest pain clinics across Scotland for assessment of suspected angina due to coronary artery disease, of whom 47% were diagnosed in the clinic with coronary heart disease and 36% with angina due to coronary heart disease. Patients were then evenly randomized to standard care involving cardiovascular risk assessment with the ASSIGN Score alone or with CTA.

When attending clinicians reviewed the cases at 6 weeks, the diagnosis of coronary heart disease (CHD) changed in 25% of patients assigned CTA vs. only 1% assigned standard care alone and the diagnosis of angina due to CHD changed in 23% vs. 1% (P value < .001 for both), Dr. Newby, from the University of Edinburgh, said.

Clinicians reported that CTA significantly increased the certainty (Relative risk, 2.56; P < .0001) and frequency (RR, 1.09; P = .017) of the diagnosis of CHD and increased the certainty of a diagnosis of angina due to CHD (RR, 1.79; P < .0001), but had no effect on its frequency (RR, 0.93; P = .12).

Overall, 63% of patients had evidence of CHD on CTA, with 25% having obstructive disease.

CTA altered subsequent testing in 15% of patients vs. only 1% with standard care (P < .001). CTA use was associated with the cancellation of 121 functional stress tests and 29 invasive coronary angiography exams. CTA also prompted 94 new angiograms vs. just 8 with standard care, but this was mainly the result of the exclusion or discovery of obstructive coronary heart disease, including triple vessel disease, Dr. Newby observed. CT was associated with a nonsignificant increase in coronary revascularizations (11.2% vs. 9.7%; HR, 1.19; P .06).

The changes in diagnosis and testing were associated with changes in subsequent treatment in 23% of CTA patients vs. 5% of standard care patients overall (P < .001), including recommendations and cancellations for preventive and anti-anginal therapies. The results were also simultaneously published online (Lancet 2015 [doi:10.19016/S0140-6736(15)060291-4]).

The most impressive aspect of SCOT-HEART was the strong trend for improved outcomes in patients for which therapeutic alterations were made, Dr. Eric Peterson, with the Duke University in Durham, N.C., commented.

“This sets the standard for how we perform and evaluate whether CT can improve outcomes for patients,” he said.

In an editorial accompanying the report,, Dr. Pamela Douglas, from the Duke Clinical Research Institute in Durham, N.C., called the finding of reduced death and MI “intriguing,” but urged caution in its interpretation because it was one of 22 secondary end points and the absolute difference between groups was only 16 events (Lancet 2015; [doi: 10.1016/S0140-6736(15)60463-9]). Earlier in the meeting, she reported that the PROMISE trial found no difference in its primary composite end point of all-cause death, nonfatal myocardial infarction, unstable angina hospitalization, and major cardiovascular procedural complications among chest pain patients evaluated with CTA or functional testing.

Finally, it was noted that radiation exposure in SCOT-HEART (median 4.1 mSv) was substantially lower than that reported in PROMISE, a finding Dr. Newby said he could not explain.

pwendling@frontlinemedcom.com

SAN DIEGO – The addition of CT angiography to standard care changed the diagnosis and treatment of one in four patients with stable chest pain in the prospective, randomized SCOT-HEART trial.

CT angiography (CTA) also reduced coronary heart disease deaths or myocardial infarctions by 38% after a median follow-up of 1.7 years, although the finding was of borderline significance (hazard ratio, 0.62; P = .053).

A post-hoc, landmark analysis, however, that accounted for the roughly 6-week delay between the clinic visit and implementation or alteration of therapy based on CTA findings, showed a halving of these outcomes (HR, 0.50; P = .015), chief investigator Dr. David Newby reported at the annual meeting of the American College of Cardiology.

SCOT-HEART (Scottish COmputed Tomography of the Heart trial) involved 4,146 patients referred from chest pain clinics across Scotland for assessment of suspected angina due to coronary artery disease, of whom 47% were diagnosed in the clinic with coronary heart disease and 36% with angina due to coronary heart disease. Patients were then evenly randomized to standard care involving cardiovascular risk assessment with the ASSIGN Score alone or with CTA.

When attending clinicians reviewed the cases at 6 weeks, the diagnosis of coronary heart disease (CHD) changed in 25% of patients assigned CTA vs. only 1% assigned standard care alone and the diagnosis of angina due to CHD changed in 23% vs. 1% (P value < .001 for both), Dr. Newby, from the University of Edinburgh, said.

Clinicians reported that CTA significantly increased the certainty (Relative risk, 2.56; P < .0001) and frequency (RR, 1.09; P = .017) of the diagnosis of CHD and increased the certainty of a diagnosis of angina due to CHD (RR, 1.79; P < .0001), but had no effect on its frequency (RR, 0.93; P = .12).

Overall, 63% of patients had evidence of CHD on CTA, with 25% having obstructive disease.

CTA altered subsequent testing in 15% of patients vs. only 1% with standard care (P < .001). CTA use was associated with the cancellation of 121 functional stress tests and 29 invasive coronary angiography exams. CTA also prompted 94 new angiograms vs. just 8 with standard care, but this was mainly the result of the exclusion or discovery of obstructive coronary heart disease, including triple vessel disease, Dr. Newby observed. CT was associated with a nonsignificant increase in coronary revascularizations (11.2% vs. 9.7%; HR, 1.19; P .06).

The changes in diagnosis and testing were associated with changes in subsequent treatment in 23% of CTA patients vs. 5% of standard care patients overall (P < .001), including recommendations and cancellations for preventive and anti-anginal therapies. The results were also simultaneously published online (Lancet 2015 [doi:10.19016/S0140-6736(15)060291-4]).

The most impressive aspect of SCOT-HEART was the strong trend for improved outcomes in patients for which therapeutic alterations were made, Dr. Eric Peterson, with the Duke University in Durham, N.C., commented.

“This sets the standard for how we perform and evaluate whether CT can improve outcomes for patients,” he said.

In an editorial accompanying the report,, Dr. Pamela Douglas, from the Duke Clinical Research Institute in Durham, N.C., called the finding of reduced death and MI “intriguing,” but urged caution in its interpretation because it was one of 22 secondary end points and the absolute difference between groups was only 16 events (Lancet 2015; [doi: 10.1016/S0140-6736(15)60463-9]). Earlier in the meeting, she reported that the PROMISE trial found no difference in its primary composite end point of all-cause death, nonfatal myocardial infarction, unstable angina hospitalization, and major cardiovascular procedural complications among chest pain patients evaluated with CTA or functional testing.

Finally, it was noted that radiation exposure in SCOT-HEART (median 4.1 mSv) was substantially lower than that reported in PROMISE, a finding Dr. Newby said he could not explain.

pwendling@frontlinemedcom.com

SAN DIEGO– The investigational PCSK9 inhibitor evolucumab dramatically reduced the 1-year cardiovascular event rate, by 53%, compared with standard statin-based lipid-lowering in the randomized OSLER study.

This reduction in adverse cardiovascular events was accompanied by a robust 61% reduction in LDL compared with standard therapy. The LDL level in evolocumab-treated patients dropped from 120 mg/dL to an average of 48 mg/dL, Dr. Marc S. Sabatine reported at the annual meeting of the American College of Cardiology.

The safety profile of patients on evolocumab plus standard, statin-based lipid lowering was essentially the same as in controls on standard therapy alone. Moreover, no gradient was seen for any adverse events on the basis of the extent of LDL lowering. For example, the types and incidence of adverse events and laboratory abnormalities in the 773 evolocumab-treated OSLER participants with an achieved LDL less than 25 mg/dL were closely similar to those seen with an LDL above 40 mg/dL, according to Dr. Sabatine, chairman of the Thrombolysis In Myocardial Infarction Study Group at Brigham and Women’s Hospital in Boston.

“These data, in conjuction with epidemiological and genetic data, offer further support for the potential for PCSK9 inhibition as a safe and effective means to reduce major adverse cardiovascular outcomes through particularly robust LDL cholesterol lowering,” he added.

OSLER (Open-Label Study of Long-Term Evaluation against LDL Cholesterol) included 4,465 patients who had completed one of a dozen earlier phase II or III studies of evolucumab, a monoclonal antibody that inhibits proprotein convertase subtilisin kexin type 9 (PCSK9), and were then randomized 2:1 to 1 year of open-label evolucumab administered subcutaneously at either 140 mg every 2 weeks or 420 mg once monthly plus standard lipid-lowering, or to standard lipid-lowering alone, generally with moderate- or high-dose statins.

The PCSK9 inhibitor reduced LDL cholesterol by 73 mg/dL compared to the control arm. In addition, the evolocumab group experienced a 26% decrease in Lp(a), a 47% drop in ApoB, a 13% reduction in triglycerides, and a 7% rise in HDL relative to standard care.

The 1-year composite cardiovascular event rate was just 0.95% in the evolucumab group, a 53% reduction relative to the 2.18% rate in the control arm. The composite outcome was comprised of death, MI, stroke or TIA, hospitalization for heart failure, coronary revascularization, or hospitalization for unstable angina. The reduction in events seen with evolocumab was consistent across all the components of the composite outcome.

Rates of most adverse events were closely similar in the two study arms. The exception was self-reported neurocognitive events such as forgetfulness or confusion, where the 0.9% incidence in the evolucumab group, while quite low in an absolute sense, was nonetheless threefold higher than in controls.

While the OSLER findings are highly encouraging in terms of both efficacy and safety, the study was too small and too brief at 1 year to be considered definitive, especially in terms of cardiovascular event rates, of which there only 60 in total. All eyes are now on the ongoing 27,500-patient, randomized, placebo-controlled FOURIER (Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk) study. Participants in FOURIER must have a history of MI, stroke, or peripheral artery disease plus at least one additional high-risk feature. Results are expected in 2017.

Similar massive pivotal phase III studies of two other highly promising PCSK9 inhibitors – alirocumab and bococizumab – are ongoing. The PCSK9 inhibitors were the talk of ACC 2015 in light of the mounting impressive safety and efficacy data. The Food and Drug Administration is now considering whether to approve PCSK9 inhibition for patients with familial hypercholesterolemia whose LDL is not adequately controlled by statins, with a decision expected later this year.

Discussant Dr. Christopher P. Cannon called OSLER “a terrific study.”

The OSLER findings, coupled with a previously reported preliminary analysis suggesting reduced cardiovascular events in clinical trials of alirocumab, provide strong support for the notion that the lower the achieved LDL – whether accomplished by statins or other agents – the greater the cardiovascular benefit.

“This is so exciting. Lowering cholesterol is definitely a passion of mine,” said Dr. Cannon, professor of medicine at Harvard Medical School, Boston.

Discussant Dr. Judith S. Hochman was equally enthusiastic about the OSLER outcomes.

“This is really impressive and very encouraging for this class of cholesterol-lowering agents. And I want to congratulate you for enrolling 50% women. But we need more study about the potential for neurocognitive events,” commented Dr. Hochman, professor of cardiology and senior associate dean for clinical sciences at New York University.

Dr. Sabatine agreed. While neurocognitive events in OSLER were self-reported by patients, FOURIER includes a substudy featuring formal neurocognitive testing using validated instruments. And while that should provide definitive answers, he said he’s not too concerned about the neurocognitive issue.

“Biologically, LDL cholesterol is not used as a source of cholesterol for cells, and that’s especially true for cells in the CNS because of the blood-brain barrier. And very low LDL levels don’t appear to have any effect on the CNS in animal models,” he said.

A more comprehensive picture of evolucumab’s safety was provided elsewhere at ACC 15 by Dr. Peter P. Toth. His safety analysis incorporated more than 6,000 evolucumab-treated patients and 3,569 controls who participated in a dozen phase II and III trials as well as OSLER.

The short version: This pooled analysis demonstrated no increase in any clinical adverse events or laboratory abnormalities with evolocumab, compared with controls. That includes muscle-related adverse events, liver or renal toxicity, impairment in glucose metabolism, infections, injection-site reactions, and neurocognitive events, said Dr. Toth of the University of Illinois, Peoria.

Simultaneous with Dr. Sabatine’s presentation at ACC 15, the OSLER results were published online (N. Engl. J. Med. 2015 [doi: 10.1056/NEJMoa1500858]).

Both OSLER and Dr. Toth’s broader safety analysis were funded by Amgen. Dr. Sabatine and Dr. Toth reported having received research grant support from and serving as consultants to Amgen and numerous other pharmaceutical companies. Dr. Hochman is a consultant to GlaxoSmithKline. Dr. Cannon has received research grant support from and served as a consultant or advisor to many pharmaceutical companies.

bjancin@frontlinemedcom.com

SAN DIEGO– The investigational PCSK9 inhibitor evolucumab dramatically reduced the 1-year cardiovascular event rate, by 53%, compared with standard statin-based lipid-lowering in the randomized OSLER study.

This reduction in adverse cardiovascular events was accompanied by a robust 61% reduction in LDL compared with standard therapy. The LDL level in evolocumab-treated patients dropped from 120 mg/dL to an average of 48 mg/dL, Dr. Marc S. Sabatine reported at the annual meeting of the American College of Cardiology.

The safety profile of patients on evolocumab plus standard, statin-based lipid lowering was essentially the same as in controls on standard therapy alone. Moreover, no gradient was seen for any adverse events on the basis of the extent of LDL lowering. For example, the types and incidence of adverse events and laboratory abnormalities in the 773 evolocumab-treated OSLER participants with an achieved LDL less than 25 mg/dL were closely similar to those seen with an LDL above 40 mg/dL, according to Dr. Sabatine, chairman of the Thrombolysis In Myocardial Infarction Study Group at Brigham and Women’s Hospital in Boston.

“These data, in conjuction with epidemiological and genetic data, offer further support for the potential for PCSK9 inhibition as a safe and effective means to reduce major adverse cardiovascular outcomes through particularly robust LDL cholesterol lowering,” he added.

OSLER (Open-Label Study of Long-Term Evaluation against LDL Cholesterol) included 4,465 patients who had completed one of a dozen earlier phase II or III studies of evolucumab, a monoclonal antibody that inhibits proprotein convertase subtilisin kexin type 9 (PCSK9), and were then randomized 2:1 to 1 year of open-label evolucumab administered subcutaneously at either 140 mg every 2 weeks or 420 mg once monthly plus standard lipid-lowering, or to standard lipid-lowering alone, generally with moderate- or high-dose statins.

The PCSK9 inhibitor reduced LDL cholesterol by 73 mg/dL compared to the control arm. In addition, the evolocumab group experienced a 26% decrease in Lp(a), a 47% drop in ApoB, a 13% reduction in triglycerides, and a 7% rise in HDL relative to standard care.

The 1-year composite cardiovascular event rate was just 0.95% in the evolucumab group, a 53% reduction relative to the 2.18% rate in the control arm. The composite outcome was comprised of death, MI, stroke or TIA, hospitalization for heart failure, coronary revascularization, or hospitalization for unstable angina. The reduction in events seen with evolocumab was consistent across all the components of the composite outcome.

Rates of most adverse events were closely similar in the two study arms. The exception was self-reported neurocognitive events such as forgetfulness or confusion, where the 0.9% incidence in the evolucumab group, while quite low in an absolute sense, was nonetheless threefold higher than in controls.

While the OSLER findings are highly encouraging in terms of both efficacy and safety, the study was too small and too brief at 1 year to be considered definitive, especially in terms of cardiovascular event rates, of which there only 60 in total. All eyes are now on the ongoing 27,500-patient, randomized, placebo-controlled FOURIER (Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk) study. Participants in FOURIER must have a history of MI, stroke, or peripheral artery disease plus at least one additional high-risk feature. Results are expected in 2017.

Similar massive pivotal phase III studies of two other highly promising PCSK9 inhibitors – alirocumab and bococizumab – are ongoing. The PCSK9 inhibitors were the talk of ACC 2015 in light of the mounting impressive safety and efficacy data. The Food and Drug Administration is now considering whether to approve PCSK9 inhibition for patients with familial hypercholesterolemia whose LDL is not adequately controlled by statins, with a decision expected later this year.

Discussant Dr. Christopher P. Cannon called OSLER “a terrific study.”

The OSLER findings, coupled with a previously reported preliminary analysis suggesting reduced cardiovascular events in clinical trials of alirocumab, provide strong support for the notion that the lower the achieved LDL – whether accomplished by statins or other agents – the greater the cardiovascular benefit.

“This is so exciting. Lowering cholesterol is definitely a passion of mine,” said Dr. Cannon, professor of medicine at Harvard Medical School, Boston.

Discussant Dr. Judith S. Hochman was equally enthusiastic about the OSLER outcomes.

“This is really impressive and very encouraging for this class of cholesterol-lowering agents. And I want to congratulate you for enrolling 50% women. But we need more study about the potential for neurocognitive events,” commented Dr. Hochman, professor of cardiology and senior associate dean for clinical sciences at New York University.

Dr. Sabatine agreed. While neurocognitive events in OSLER were self-reported by patients, FOURIER includes a substudy featuring formal neurocognitive testing using validated instruments. And while that should provide definitive answers, he said he’s not too concerned about the neurocognitive issue.

“Biologically, LDL cholesterol is not used as a source of cholesterol for cells, and that’s especially true for cells in the CNS because of the blood-brain barrier. And very low LDL levels don’t appear to have any effect on the CNS in animal models,” he said.

A more comprehensive picture of evolucumab’s safety was provided elsewhere at ACC 15 by Dr. Peter P. Toth. His safety analysis incorporated more than 6,000 evolucumab-treated patients and 3,569 controls who participated in a dozen phase II and III trials as well as OSLER.

The short version: This pooled analysis demonstrated no increase in any clinical adverse events or laboratory abnormalities with evolocumab, compared with controls. That includes muscle-related adverse events, liver or renal toxicity, impairment in glucose metabolism, infections, injection-site reactions, and neurocognitive events, said Dr. Toth of the University of Illinois, Peoria.

Simultaneous with Dr. Sabatine’s presentation at ACC 15, the OSLER results were published online (N. Engl. J. Med. 2015 [doi: 10.1056/NEJMoa1500858]).

Both OSLER and Dr. Toth’s broader safety analysis were funded by Amgen. Dr. Sabatine and Dr. Toth reported having received research grant support from and serving as consultants to Amgen and numerous other pharmaceutical companies. Dr. Hochman is a consultant to GlaxoSmithKline. Dr. Cannon has received research grant support from and served as a consultant or advisor to many pharmaceutical companies.

bjancin@frontlinemedcom.com

SAN DIEGO– The investigational PCSK9 inhibitor evolucumab dramatically reduced the 1-year cardiovascular event rate, by 53%, compared with standard statin-based lipid-lowering in the randomized OSLER study.

This reduction in adverse cardiovascular events was accompanied by a robust 61% reduction in LDL compared with standard therapy. The LDL level in evolocumab-treated patients dropped from 120 mg/dL to an average of 48 mg/dL, Dr. Marc S. Sabatine reported at the annual meeting of the American College of Cardiology.

The safety profile of patients on evolocumab plus standard, statin-based lipid lowering was essentially the same as in controls on standard therapy alone. Moreover, no gradient was seen for any adverse events on the basis of the extent of LDL lowering. For example, the types and incidence of adverse events and laboratory abnormalities in the 773 evolocumab-treated OSLER participants with an achieved LDL less than 25 mg/dL were closely similar to those seen with an LDL above 40 mg/dL, according to Dr. Sabatine, chairman of the Thrombolysis In Myocardial Infarction Study Group at Brigham and Women’s Hospital in Boston.

“These data, in conjuction with epidemiological and genetic data, offer further support for the potential for PCSK9 inhibition as a safe and effective means to reduce major adverse cardiovascular outcomes through particularly robust LDL cholesterol lowering,” he added.

OSLER (Open-Label Study of Long-Term Evaluation against LDL Cholesterol) included 4,465 patients who had completed one of a dozen earlier phase II or III studies of evolucumab, a monoclonal antibody that inhibits proprotein convertase subtilisin kexin type 9 (PCSK9), and were then randomized 2:1 to 1 year of open-label evolucumab administered subcutaneously at either 140 mg every 2 weeks or 420 mg once monthly plus standard lipid-lowering, or to standard lipid-lowering alone, generally with moderate- or high-dose statins.

The PCSK9 inhibitor reduced LDL cholesterol by 73 mg/dL compared to the control arm. In addition, the evolocumab group experienced a 26% decrease in Lp(a), a 47% drop in ApoB, a 13% reduction in triglycerides, and a 7% rise in HDL relative to standard care.

The 1-year composite cardiovascular event rate was just 0.95% in the evolucumab group, a 53% reduction relative to the 2.18% rate in the control arm. The composite outcome was comprised of death, MI, stroke or TIA, hospitalization for heart failure, coronary revascularization, or hospitalization for unstable angina. The reduction in events seen with evolocumab was consistent across all the components of the composite outcome.

Rates of most adverse events were closely similar in the two study arms. The exception was self-reported neurocognitive events such as forgetfulness or confusion, where the 0.9% incidence in the evolucumab group, while quite low in an absolute sense, was nonetheless threefold higher than in controls.

While the OSLER findings are highly encouraging in terms of both efficacy and safety, the study was too small and too brief at 1 year to be considered definitive, especially in terms of cardiovascular event rates, of which there only 60 in total. All eyes are now on the ongoing 27,500-patient, randomized, placebo-controlled FOURIER (Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk) study. Participants in FOURIER must have a history of MI, stroke, or peripheral artery disease plus at least one additional high-risk feature. Results are expected in 2017.

Similar massive pivotal phase III studies of two other highly promising PCSK9 inhibitors – alirocumab and bococizumab – are ongoing. The PCSK9 inhibitors were the talk of ACC 2015 in light of the mounting impressive safety and efficacy data. The Food and Drug Administration is now considering whether to approve PCSK9 inhibition for patients with familial hypercholesterolemia whose LDL is not adequately controlled by statins, with a decision expected later this year.

Discussant Dr. Christopher P. Cannon called OSLER “a terrific study.”

The OSLER findings, coupled with a previously reported preliminary analysis suggesting reduced cardiovascular events in clinical trials of alirocumab, provide strong support for the notion that the lower the achieved LDL – whether accomplished by statins or other agents – the greater the cardiovascular benefit.

“This is so exciting. Lowering cholesterol is definitely a passion of mine,” said Dr. Cannon, professor of medicine at Harvard Medical School, Boston.

Discussant Dr. Judith S. Hochman was equally enthusiastic about the OSLER outcomes.

“This is really impressive and very encouraging for this class of cholesterol-lowering agents. And I want to congratulate you for enrolling 50% women. But we need more study about the potential for neurocognitive events,” commented Dr. Hochman, professor of cardiology and senior associate dean for clinical sciences at New York University.

Dr. Sabatine agreed. While neurocognitive events in OSLER were self-reported by patients, FOURIER includes a substudy featuring formal neurocognitive testing using validated instruments. And while that should provide definitive answers, he said he’s not too concerned about the neurocognitive issue.

“Biologically, LDL cholesterol is not used as a source of cholesterol for cells, and that’s especially true for cells in the CNS because of the blood-brain barrier. And very low LDL levels don’t appear to have any effect on the CNS in animal models,” he said.

A more comprehensive picture of evolucumab’s safety was provided elsewhere at ACC 15 by Dr. Peter P. Toth. His safety analysis incorporated more than 6,000 evolucumab-treated patients and 3,569 controls who participated in a dozen phase II and III trials as well as OSLER.

The short version: This pooled analysis demonstrated no increase in any clinical adverse events or laboratory abnormalities with evolocumab, compared with controls. That includes muscle-related adverse events, liver or renal toxicity, impairment in glucose metabolism, infections, injection-site reactions, and neurocognitive events, said Dr. Toth of the University of Illinois, Peoria.

Simultaneous with Dr. Sabatine’s presentation at ACC 15, the OSLER results were published online (N. Engl. J. Med. 2015 [doi: 10.1056/NEJMoa1500858]).

Both OSLER and Dr. Toth’s broader safety analysis were funded by Amgen. Dr. Sabatine and Dr. Toth reported having received research grant support from and serving as consultants to Amgen and numerous other pharmaceutical companies. Dr. Hochman is a consultant to GlaxoSmithKline. Dr. Cannon has received research grant support from and served as a consultant or advisor to many pharmaceutical companies.

bjancin@frontlinemedcom.com

SAN DIEGO – Five years out, transcatheter aortic valve replacement beat standard therapy in patients with severe, inoperable aortic stenosis, and measured up to surgery in high-risk patients.

The final data from the PARTNER 1 data showed TAVR as an alternative to surgery for some high-risk surgical patients, Dr. Michael Mack reported at the annual scientific sessions of the American College of Cardiology. High-risk surgical patients had similar all-cause mortality, cardiovascular mortality, stroke, and hospital readmission rates, regardless of whether they underwent TAVR or surgical valve replacement, Dr. Mack of Baylor Scott & White Health in Plano, Texas, and his associates wrote in an article published online simultaneously with the presentation (Lancet 2015 Mar. 15 [doi: 10.1016/ S0140-6736(15)60308-7]). “Functional outcomes were also similar and preservation of valve hemodynamics was equivalent in both groups,” they wrote.

The trial also showed “a sustained benefit of TAVR” for inoperable aortic stenosis, “as measured by all-cause mortality, cardiovascular mortality, repeat hospital admission, and functional status. Valves were durable, with no increase in transvalvular gradient, attrition of valve area, or worsening of aortic regurgitation,” Dr. Samir Kapadia at the Cleveland Clinic in Ohio and his associates reported in an related article that was not presented at the ACC meeting but was published at the same time as Dr. Mack’s presentation (Lancet 2015 Mar. 15 [doi: 10.1016/ S0140-6736(15)60290-2]). Based on the findings, “TAVR should be strongly considered for patients who are not surgical candidates for aortic valve replacement,” the researchers added. “Appropriate selection of patients will help to maximize the benefit of TAVR and reduce mortality from coexisting severe comorbidities.”

The Placement of Aortic Transcatheter Valves (PARTNER 1) trial compared TAVR, standard nonsurgical treatment, and surgery in patients with severe, symptomatic aortic stenosis. The inoperable cohort included 358 patients who averaged 83 years of age. The high-risk cohort enrolled 699 patients whose overall average Society of Thoracic Surgeons (STS) Predicted Risk of Mortality Score was more than 11%. Inoperable patients were randomized to TAVR or standard treatment (usually including balloon aortic valvuloplasty), while high-risk patients were randomized to TAVR or surgical valve replacement.

Five years after treatment, almost 72% of TAVR patients in the inoperable cohort had died, compared with 94% of patients who received standard treatment (hazard ratio, 0.50; 95% confidence interval, 0.39-0.65; P < .0001), Dr. Kapadia and his associates reported. Notably, 86% (or 42 of 49) of surviving TAVR patients had New York Heart Association class 1 or 2 symptoms, compared with only 60% of patients who received standard treatment. Echocardiography did not reveal valve deterioration, the investigators said.

Patients in the high-risk group also faced substantial mortality – only about a third were alive 5 years after TAVR or surgery, Dr. Mack reported. Also, 14% of TAVR patients developed moderate to severe valvular regurgitation, compared with only 1% of the surgery group; P < .0001), and this complication was tied to lower survival, they wrote. “The clinical outcomes and valve performance in this trial might not reflect that of subsequent generations of balloon-expandable transcatheter valves, present operator expertise and experience, and more rigorous patient selection for TAVR,” he cautioned. “The patients selected for treatment in this trial, which started in 2007, are also representative of clinical practice at that time; clinicians have since refined patient selection, at least partly on the basis of early outcomes from this trial.”

Edwards Lifesciences funded the study. Several authors reported receiving travel reimbursements from Edwards Lifesciences and financial or consulting relationships with Abbott Vascular, Edwards Lifesciences, Medtronic, Thubrikar Aortic Valve, St Jude Medical, Philips Healthcare, Sorin Medical, DirectFlow, Boston Scientific, Cardiosolutions, ValvXchange, and Posthorax.

SAN DIEGO – Five years out, transcatheter aortic valve replacement beat standard therapy in patients with severe, inoperable aortic stenosis, and measured up to surgery in high-risk patients.

The final data from the PARTNER 1 data showed TAVR as an alternative to surgery for some high-risk surgical patients, Dr. Michael Mack reported at the annual scientific sessions of the American College of Cardiology. High-risk surgical patients had similar all-cause mortality, cardiovascular mortality, stroke, and hospital readmission rates, regardless of whether they underwent TAVR or surgical valve replacement, Dr. Mack of Baylor Scott & White Health in Plano, Texas, and his associates wrote in an article published online simultaneously with the presentation (Lancet 2015 Mar. 15 [doi: 10.1016/ S0140-6736(15)60308-7]). “Functional outcomes were also similar and preservation of valve hemodynamics was equivalent in both groups,” they wrote.

The trial also showed “a sustained benefit of TAVR” for inoperable aortic stenosis, “as measured by all-cause mortality, cardiovascular mortality, repeat hospital admission, and functional status. Valves were durable, with no increase in transvalvular gradient, attrition of valve area, or worsening of aortic regurgitation,” Dr. Samir Kapadia at the Cleveland Clinic in Ohio and his associates reported in an related article that was not presented at the ACC meeting but was published at the same time as Dr. Mack’s presentation (Lancet 2015 Mar. 15 [doi: 10.1016/ S0140-6736(15)60290-2]). Based on the findings, “TAVR should be strongly considered for patients who are not surgical candidates for aortic valve replacement,” the researchers added. “Appropriate selection of patients will help to maximize the benefit of TAVR and reduce mortality from coexisting severe comorbidities.”

The Placement of Aortic Transcatheter Valves (PARTNER 1) trial compared TAVR, standard nonsurgical treatment, and surgery in patients with severe, symptomatic aortic stenosis. The inoperable cohort included 358 patients who averaged 83 years of age. The high-risk cohort enrolled 699 patients whose overall average Society of Thoracic Surgeons (STS) Predicted Risk of Mortality Score was more than 11%. Inoperable patients were randomized to TAVR or standard treatment (usually including balloon aortic valvuloplasty), while high-risk patients were randomized to TAVR or surgical valve replacement.

Five years after treatment, almost 72% of TAVR patients in the inoperable cohort had died, compared with 94% of patients who received standard treatment (hazard ratio, 0.50; 95% confidence interval, 0.39-0.65; P < .0001), Dr. Kapadia and his associates reported. Notably, 86% (or 42 of 49) of surviving TAVR patients had New York Heart Association class 1 or 2 symptoms, compared with only 60% of patients who received standard treatment. Echocardiography did not reveal valve deterioration, the investigators said.

Patients in the high-risk group also faced substantial mortality – only about a third were alive 5 years after TAVR or surgery, Dr. Mack reported. Also, 14% of TAVR patients developed moderate to severe valvular regurgitation, compared with only 1% of the surgery group; P < .0001), and this complication was tied to lower survival, they wrote. “The clinical outcomes and valve performance in this trial might not reflect that of subsequent generations of balloon-expandable transcatheter valves, present operator expertise and experience, and more rigorous patient selection for TAVR,” he cautioned. “The patients selected for treatment in this trial, which started in 2007, are also representative of clinical practice at that time; clinicians have since refined patient selection, at least partly on the basis of early outcomes from this trial.”

Edwards Lifesciences funded the study. Several authors reported receiving travel reimbursements from Edwards Lifesciences and financial or consulting relationships with Abbott Vascular, Edwards Lifesciences, Medtronic, Thubrikar Aortic Valve, St Jude Medical, Philips Healthcare, Sorin Medical, DirectFlow, Boston Scientific, Cardiosolutions, ValvXchange, and Posthorax.

SAN DIEGO – Five years out, transcatheter aortic valve replacement beat standard therapy in patients with severe, inoperable aortic stenosis, and measured up to surgery in high-risk patients.

The final data from the PARTNER 1 data showed TAVR as an alternative to surgery for some high-risk surgical patients, Dr. Michael Mack reported at the annual scientific sessions of the American College of Cardiology. High-risk surgical patients had similar all-cause mortality, cardiovascular mortality, stroke, and hospital readmission rates, regardless of whether they underwent TAVR or surgical valve replacement, Dr. Mack of Baylor Scott & White Health in Plano, Texas, and his associates wrote in an article published online simultaneously with the presentation (Lancet 2015 Mar. 15 [doi: 10.1016/ S0140-6736(15)60308-7]). “Functional outcomes were also similar and preservation of valve hemodynamics was equivalent in both groups,” they wrote.

The trial also showed “a sustained benefit of TAVR” for inoperable aortic stenosis, “as measured by all-cause mortality, cardiovascular mortality, repeat hospital admission, and functional status. Valves were durable, with no increase in transvalvular gradient, attrition of valve area, or worsening of aortic regurgitation,” Dr. Samir Kapadia at the Cleveland Clinic in Ohio and his associates reported in an related article that was not presented at the ACC meeting but was published at the same time as Dr. Mack’s presentation (Lancet 2015 Mar. 15 [doi: 10.1016/ S0140-6736(15)60290-2]). Based on the findings, “TAVR should be strongly considered for patients who are not surgical candidates for aortic valve replacement,” the researchers added. “Appropriate selection of patients will help to maximize the benefit of TAVR and reduce mortality from coexisting severe comorbidities.”

The Placement of Aortic Transcatheter Valves (PARTNER 1) trial compared TAVR, standard nonsurgical treatment, and surgery in patients with severe, symptomatic aortic stenosis. The inoperable cohort included 358 patients who averaged 83 years of age. The high-risk cohort enrolled 699 patients whose overall average Society of Thoracic Surgeons (STS) Predicted Risk of Mortality Score was more than 11%. Inoperable patients were randomized to TAVR or standard treatment (usually including balloon aortic valvuloplasty), while high-risk patients were randomized to TAVR or surgical valve replacement.

Five years after treatment, almost 72% of TAVR patients in the inoperable cohort had died, compared with 94% of patients who received standard treatment (hazard ratio, 0.50; 95% confidence interval, 0.39-0.65; P < .0001), Dr. Kapadia and his associates reported. Notably, 86% (or 42 of 49) of surviving TAVR patients had New York Heart Association class 1 or 2 symptoms, compared with only 60% of patients who received standard treatment. Echocardiography did not reveal valve deterioration, the investigators said.

Patients in the high-risk group also faced substantial mortality – only about a third were alive 5 years after TAVR or surgery, Dr. Mack reported. Also, 14% of TAVR patients developed moderate to severe valvular regurgitation, compared with only 1% of the surgery group; P < .0001), and this complication was tied to lower survival, they wrote. “The clinical outcomes and valve performance in this trial might not reflect that of subsequent generations of balloon-expandable transcatheter valves, present operator expertise and experience, and more rigorous patient selection for TAVR,” he cautioned. “The patients selected for treatment in this trial, which started in 2007, are also representative of clinical practice at that time; clinicians have since refined patient selection, at least partly on the basis of early outcomes from this trial.”

Edwards Lifesciences funded the study. Several authors reported receiving travel reimbursements from Edwards Lifesciences and financial or consulting relationships with Abbott Vascular, Edwards Lifesciences, Medtronic, Thubrikar Aortic Valve, St Jude Medical, Philips Healthcare, Sorin Medical, DirectFlow, Boston Scientific, Cardiosolutions, ValvXchange, and Posthorax.

SAN DIEGO – Initial anatomic testing with CT angiography yielded similar clinical outcomes to functional testing in chest pain patients evaluated for coronary artery disease in the PROMISE study.

After an average of 25 months, the primary composite end point of all-cause death, nonfatal myocardial infarction, unstable angina hospitalization, and major cardiovascular procedural complications occurred in 3.3% of the CTA patients and 3.0% of the functional-testing patients (adjusted hazard ratio, 1.04; P = .75).

The CTA strategy may offer a slight advantage, however, in terms of fewer invasive catheterizations without evidence of obstructive coronary artery disease (3.4% vs. 4.3%; P = .022) and a higher proportion of catheterizations with obstructive CAD (72.1% vs. 47.5%) getting revascularization (6.2% vs. 3.2%) or coronary artery bypass grafting (72 events vs. 38 events).

“Our results suggest that CTA is a viable alternative to functional testing. These real-world results should inform noninvasive testing choices in clinical care as well as provide guidance to future studies of diagnostic strategies in suspected heart disease,” lead study author Dr. Pamela Douglas reported at the annual meeting of the American College of Cardiology and simultaneously published online (N. Engl. J. Med. 2015 [DOI:10.1056/NEJoa1415516].

Patrice Wendling/Frontline Medical News

PROMISE (Prospective Multicenter Imaging Study for the Evaluation of Chest Pain) enrolled 10,003 symptomatic outpatients requiring nonemergent, noninvasive testing for suspected CAD who were older than 54 years for men or older than 64 years for women with no risk factors, or aged 45-54 years for men and 50-64 years for women with at least one cardiac risk factor.

Patients were randomly assigned to anatomical testing with CTA or functional testing including a nuclear stress test (67%), stress echocardiography (23%), or exercise electrocardiogram (10%). The patients had an average of 2.5 risk cardiovascular risk factors and half were women.

Radiation exposure was higher overall in the CTA group than the functional-testing group (mean 12.0 mSv vs. 10.1 mSv; P < .001), largely because 33% of the functional group had no exposure. Exposure was lower, however, in CTA patients compared with those for whom a nuclear test was specified at randomization as their first intended functional test (12.0 mSv vs. 14.1 mSv; P < .001), Dr. Douglas, from Duke Clinical Research Institute in Durham, N.C., said.

During a discussion of the results, Dr. Elliott Antman, associate dean for clinical and translational research at Harvard University, Boston, said CT angiography can’t officially be described as noninferior to functional testing because PROMISE was designed as a superiority trial with a noninferiority margin that was exceeded by the confidence intervals for the primary end point and questioned how clinicians should use the results.

“What I can say to the next patient is that they can be incredibly assured about their overall prognosis, which is a nontrivial thing to say that they have a very, very low likelihood of a bad event in the next 2 years no matter what we do,” Dr. Douglas responded. “I can offer a test choice that will have no difference in major health events like death or nonfatal MI, but I can offer a test that potentially has lower radiation and has a better triage function to the cath lab where you have less likelihood of ending up in the cath lab not needing to be there because you do not have obstructive disease.”

Though PROMISE may influence practice, it is unclear whether the noninferiority issue will impact its ability to change U.S. guidelines, which currently include a IIb recommendation that CTA be considered in the evaluation of patients with chest pain.

“Technically two randomized controlled trials are needed before you get evidence level A, but we have 10,000 patients who were well studied here, so I would anticipate a big change actually in the guidelines from a use criteria, but we shall see,” Dr. Douglas said.

pwendling@frontlinemedcom.com

SAN DIEGO – Initial anatomic testing with CT angiography yielded similar clinical outcomes to functional testing in chest pain patients evaluated for coronary artery disease in the PROMISE study.

After an average of 25 months, the primary composite end point of all-cause death, nonfatal myocardial infarction, unstable angina hospitalization, and major cardiovascular procedural complications occurred in 3.3% of the CTA patients and 3.0% of the functional-testing patients (adjusted hazard ratio, 1.04; P = .75).

The CTA strategy may offer a slight advantage, however, in terms of fewer invasive catheterizations without evidence of obstructive coronary artery disease (3.4% vs. 4.3%; P = .022) and a higher proportion of catheterizations with obstructive CAD (72.1% vs. 47.5%) getting revascularization (6.2% vs. 3.2%) or coronary artery bypass grafting (72 events vs. 38 events).

“Our results suggest that CTA is a viable alternative to functional testing. These real-world results should inform noninvasive testing choices in clinical care as well as provide guidance to future studies of diagnostic strategies in suspected heart disease,” lead study author Dr. Pamela Douglas reported at the annual meeting of the American College of Cardiology and simultaneously published online (N. Engl. J. Med. 2015 [DOI:10.1056/NEJoa1415516].

Patrice Wendling/Frontline Medical News

PROMISE (Prospective Multicenter Imaging Study for the Evaluation of Chest Pain) enrolled 10,003 symptomatic outpatients requiring nonemergent, noninvasive testing for suspected CAD who were older than 54 years for men or older than 64 years for women with no risk factors, or aged 45-54 years for men and 50-64 years for women with at least one cardiac risk factor.

Patients were randomly assigned to anatomical testing with CTA or functional testing including a nuclear stress test (67%), stress echocardiography (23%), or exercise electrocardiogram (10%). The patients had an average of 2.5 risk cardiovascular risk factors and half were women.

Radiation exposure was higher overall in the CTA group than the functional-testing group (mean 12.0 mSv vs. 10.1 mSv; P < .001), largely because 33% of the functional group had no exposure. Exposure was lower, however, in CTA patients compared with those for whom a nuclear test was specified at randomization as their first intended functional test (12.0 mSv vs. 14.1 mSv; P < .001), Dr. Douglas, from Duke Clinical Research Institute in Durham, N.C., said.

During a discussion of the results, Dr. Elliott Antman, associate dean for clinical and translational research at Harvard University, Boston, said CT angiography can’t officially be described as noninferior to functional testing because PROMISE was designed as a superiority trial with a noninferiority margin that was exceeded by the confidence intervals for the primary end point and questioned how clinicians should use the results.

“What I can say to the next patient is that they can be incredibly assured about their overall prognosis, which is a nontrivial thing to say that they have a very, very low likelihood of a bad event in the next 2 years no matter what we do,” Dr. Douglas responded. “I can offer a test choice that will have no difference in major health events like death or nonfatal MI, but I can offer a test that potentially has lower radiation and has a better triage function to the cath lab where you have less likelihood of ending up in the cath lab not needing to be there because you do not have obstructive disease.”

Though PROMISE may influence practice, it is unclear whether the noninferiority issue will impact its ability to change U.S. guidelines, which currently include a IIb recommendation that CTA be considered in the evaluation of patients with chest pain.

“Technically two randomized controlled trials are needed before you get evidence level A, but we have 10,000 patients who were well studied here, so I would anticipate a big change actually in the guidelines from a use criteria, but we shall see,” Dr. Douglas said.

pwendling@frontlinemedcom.com

SAN DIEGO – Initial anatomic testing with CT angiography yielded similar clinical outcomes to functional testing in chest pain patients evaluated for coronary artery disease in the PROMISE study.

After an average of 25 months, the primary composite end point of all-cause death, nonfatal myocardial infarction, unstable angina hospitalization, and major cardiovascular procedural complications occurred in 3.3% of the CTA patients and 3.0% of the functional-testing patients (adjusted hazard ratio, 1.04; P = .75).

The CTA strategy may offer a slight advantage, however, in terms of fewer invasive catheterizations without evidence of obstructive coronary artery disease (3.4% vs. 4.3%; P = .022) and a higher proportion of catheterizations with obstructive CAD (72.1% vs. 47.5%) getting revascularization (6.2% vs. 3.2%) or coronary artery bypass grafting (72 events vs. 38 events).

“Our results suggest that CTA is a viable alternative to functional testing. These real-world results should inform noninvasive testing choices in clinical care as well as provide guidance to future studies of diagnostic strategies in suspected heart disease,” lead study author Dr. Pamela Douglas reported at the annual meeting of the American College of Cardiology and simultaneously published online (N. Engl. J. Med. 2015 [DOI:10.1056/NEJoa1415516].

Patrice Wendling/Frontline Medical News

PROMISE (Prospective Multicenter Imaging Study for the Evaluation of Chest Pain) enrolled 10,003 symptomatic outpatients requiring nonemergent, noninvasive testing for suspected CAD who were older than 54 years for men or older than 64 years for women with no risk factors, or aged 45-54 years for men and 50-64 years for women with at least one cardiac risk factor.

Patients were randomly assigned to anatomical testing with CTA or functional testing including a nuclear stress test (67%), stress echocardiography (23%), or exercise electrocardiogram (10%). The patients had an average of 2.5 risk cardiovascular risk factors and half were women.

Radiation exposure was higher overall in the CTA group than the functional-testing group (mean 12.0 mSv vs. 10.1 mSv; P < .001), largely because 33% of the functional group had no exposure. Exposure was lower, however, in CTA patients compared with those for whom a nuclear test was specified at randomization as their first intended functional test (12.0 mSv vs. 14.1 mSv; P < .001), Dr. Douglas, from Duke Clinical Research Institute in Durham, N.C., said.

During a discussion of the results, Dr. Elliott Antman, associate dean for clinical and translational research at Harvard University, Boston, said CT angiography can’t officially be described as noninferior to functional testing because PROMISE was designed as a superiority trial with a noninferiority margin that was exceeded by the confidence intervals for the primary end point and questioned how clinicians should use the results.

“What I can say to the next patient is that they can be incredibly assured about their overall prognosis, which is a nontrivial thing to say that they have a very, very low likelihood of a bad event in the next 2 years no matter what we do,” Dr. Douglas responded. “I can offer a test choice that will have no difference in major health events like death or nonfatal MI, but I can offer a test that potentially has lower radiation and has a better triage function to the cath lab where you have less likelihood of ending up in the cath lab not needing to be there because you do not have obstructive disease.”

Though PROMISE may influence practice, it is unclear whether the noninferiority issue will impact its ability to change U.S. guidelines, which currently include a IIb recommendation that CTA be considered in the evaluation of patients with chest pain.

“Technically two randomized controlled trials are needed before you get evidence level A, but we have 10,000 patients who were well studied here, so I would anticipate a big change actually in the guidelines from a use criteria, but we shall see,” Dr. Douglas said.

pwendling@frontlinemedcom.com