ACC 2015

Cardiology Review® Online, April 2015, Volume 31, Issue 2

More than 13,000 physicians and cardiovascular team members attended the ACC 2015 meeting in San Diego on March 14-16, 2015. In this issue of Cardiology Review, we focus on 6 important studies presented at ACC 2015: LEGACY, OSLER, PEGASUS, EMBRACE-STEMI, MATRIX, and CoreValve.

ACC 2015

64th Annual Scientific Session

March 14-16, 2015

San Diego, CA

More than 13,000 physicians and cardiovascular team members attended the ACC 2015 meeting in San Diego on March 14-16, 2015. In this issue of Cardiology Review, we focus on 6 important studies presented at ACC 2015: LEGACY, OSLER, PEGASUS, EMBRACE-STEMI, MATRIX, and CoreValve.

Long-Term Weight Loss Leads to Bigger Reductions in Severe Atrial Fibrillation Symptoms

Findings from LEGACY (Long-Term Effect of Goal Directed Weight Management on an Atrial Fibrillation Cohort), the first study to track long-term effects of weight loss and the degree of weight fluctuation on atrial fibrillation (AF) burden, show that obese patients with AF who lost at least 10% of their body weight were 6 times more likely to achieve long-term freedom from AF compared with those who didn’t lose weight.

According to lead author Rajeev Pathak, MD, cardiologist and electrophysiology fellow at the University of Adelaide and Royal Adelaide Hospital, Australia, sustained weight loss is achievable in obese patients and it can significantly reduce the burden of AF. “Weight loss also led to favorable changes in cardiovascular risk factors such as high blood pressure, obstructive sleep apnea, and diabetes, along with improvements in the structure and function of the heart,” he said.

LEGACY included 355 adults with AF and a body mass index (BMI) of at least 27 kg/m2. Their health was tracked annually for an average of 4 years. To encourage weight loss, the weight management program used face-to-face sessions, goal setting, and behavior modification, with 3 in-person visits per month, low-intensity exercise, support counseling, and maintenance of a physical activity diary.

The study annually monitored AF, assessing frequency, duration, and severity of symptoms, patient-completed questionnaires, and use of Holter monitors for 7 days, as well as an echocardiogram and sonogram of the heart.

After an average of 4 years, 45% of the patients who lost ≥10% of body weight and 22% of patients who lost 3% to 9% of their weight achieved freedom from AF symptoms without the use of any surgery or medication. However, only 13% of patients who lost <3% of body weight were free of symptoms without treatments.

Interestingly, sustained weight management and a linear trajectory of weight loss were also associated with greater freedom from AF symptoms; patients who lost and regained weight with a fluctuation of more than 5% between annual visits were twice as likely to have recurrent rhythm problems as those who did not have fluctuations in weight.

The study was published online March 16, 2015, in the Journal of the American College of Cardiology.

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PCSK9 Inhibitor Evolocumab Dramatically Lowers LDL

Results of the OSLER-1(Open-Label Study of Long-Term Evaluation Against LDL-C) trial suggests that evolocumab (Repatha), the investigational inhibitor of proprotein convertase subtilisin-kexin type 9 (PCSK9), plus standard therapy reduced low-density lipoprotein (LDL) cholesterol by 61% after 11 months of use versus standard therapy alone. The medication was also associated with reduced incidence of cardiovascular events such as myocardial infarction, heart failure requiring hospitalization, and death.

The study randomly assigned 4465 patients who had previously participated in parent trials of evolocumab to receive the medication (140 mg every 2 weeks or 420 mg monthly) plus standard therapy or standard therapy alone. Patients were followed for approximately 1 year. The primary end point was incidence of treatment-related adverse events; secondary end points included LDL-cholesterol changes from baseline.

Investigators reported that patients receiving evolocumab had a 61% drop in LDL from a median of 120 mg/dL to 38 mg/dL. Results were sustained through the median 11-month follow-up. There was evidence of reduction in the rate of cardiovascular events among patients in the evolocumab group. At 1 year the rate of cardiovascular events was lower (0.95%) in the evolocumab group compared with the standard care group (2.18%).

A total of 69.2% of the evolocumab group and 64.8% of the standard therapy group reported an adverse event and 7.5% of each group reported a serious adverse event. The rate of neurocognitive adverse events, though low overall, was higher in the PCSK9 group than in the standard therapy group (0.9% vs 0.3%).

Marc Sabatine, MD, MPH, FACC, of Brigham & Women’s Hospital, lead author of the study, said the LDL reduction was profound and may be behind the marked reduction in cardiovascular events that was seen so quickly. He noted that results are limited by the nature of the trial and that his team will shortly undertake a large-scale study, with results expected by 2017.

The study was published on March 15, 2015 in The New England Journal of Medicine.

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Adding Ticagrelor to Aspirin Reduced Risk of Second Cardiac Event

Stable heart attack patients who were prescribed ticagrelor (Brilinta) in addition to low-dose aspirin have lower risks of experiencing a secondary cardiac event, death, or stroke even after 1 year, according to results of the PEGASUS-TIMI 54 trial.

The study followed 21,162 patients with a history of myocardial infarction (MI) who had additional risk factors such as diabetes or age and who’d had a myocardial infarction (MI) 1 to 3 years prior to the study. Patients were randomly assigned to a twice-daily regimen of ticagrelor 90 mg, ticagrelor 60 mg, or placebo.

Lead investigator Marc S. Sabatine, MD, MPH, FACC, said that both patient populations receiving ticagrelor plus aspirin had reduced chances of cardiovascular mortality, MI, and stroke. The patients taking 90 mg ticagrelor had a 15% decrease in risk of experiencing a second cardiac event, and patients in the 60 mg group had a risk reduction of 16% compared with placebo. However, patients had a 2.3-fold and 2.6-fold higher risk of clinically significant bleeding and a 3.0-fold and 3.7-fold higher risk of transfusion with low-dose and high-dose ticagrelor, respectively, compared with patients taking placebo. Ticagrelor was also associated with an approximately3-fold greater risk of dyspnea, and about 30% of patients discontinued the study drug.

Because the rates of bleeding, dyspnea, and discontinuation were higher with the higher dose of ticagrelor, in general the 60-mg dose may offer a more attractive risk-benefit profile, the investigators said.

Dr Sabatine said that overall, long-term dual antiplatelet therapy with low-dose aspirin and ticagrelor should be considered for appropriate patients with an MI. “The event curves started to separate early and continue to diverge over time, suggesting that the benefit continues to accrue over time.” There was no difference in fatal bleeding or intracranial hemorrhage, Dr Sabatine noted. Rates of TIMI major bleeding were higher with ticagrelor (2.60% with 90 mg and 2.30% with 60 mg) than with placebo (1.06%). However, the study excluded patients with recent bleeding, prior stroke, or the need for anticoagulant, so the safety profile of long-term ticagrelor should not be generalized to include people at high risk of bleeding, researchers noted.

The study was published online in The New England Journal of Medicineon March 14, 2015.

AstraZeneca sponsored the trial. Disclosures are listed in the article.

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Investigational Drug Does Not Block MI Reperfusion Injury

Investigators for the phase 2a EMBRACE-STEMI trial reported that the novel intravenous mitochondria-targeting peptide Bendavia failed to minimize reperfusion injury in patients with ST-segment elevation myocardial infarction (STEMI). The drug had limited infarct size in animal studies 10% to 40% of the time. Dr C. Michael Gibson of Harvard Medical School, who presented the study data, said there have been many attempts to try to minimize reperfusion injury, usually caused by inflammatory processes.

The trial followed STEMI patients who received primary percutaneous coronary intervention (PCI), stenting, and Bendavia or placebo. There was no significant difference in the area under the curve (AUC) for the creatine kinase-MB (CK-MB) enzyme in patients who received the drug or placebo and there was no difference in AUC for troponin.

Dr Gibson said that with just 118 patients they were underpowered to detect a difference, as 800 to 1000 patients are needed for this difference to be significant. He noted that analysis did show a trend of a reduction in chronic heart failure.

Dr Gibson explained that this research takes a whole new approach to heart failure in that instead of trying to get the heart to beat harder and faster, here an attempt was made to give the heart more supply and more energy.

There were no significant differences in treatment-emergent adverse events between groups: 2% of patients in the placebo group and 6.7% of patients in the study group died.

Research grant support was provided by Stealth Pharmaceuticals and paid to Beth Israel Deaconess Medical Center.

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MATRIX: Radial PCI Reduces Major Bleeding, Mortality in ACS

Percutaneous intervention (PCI) performed via the radial artery results in a significant reduction in adverse events, according to results from the MATRIX multicenter superiority trial. The trial investigators, led by Marco Balgimigli, MD, PhD, of Erasmus Medical College in Rotterdam, The Netherlands, consider the results of the MATRIX trial so compelling that they say radial access should be the first approach for interventionalists treating ACS patients undergoing invasive management.

The MATRIX trial compared transradial versus transfemoral access in 8404 patients with acute coronary syndrome (ACS), 48% of whom were STEMI patients. After coronary angiography, approximately 80% of all patients underwent PCI.The composite end point, which included death, MI, stroke, and major bleeding, was driven by a statistically significant 33% relative reduction in the rate of major bleeding and a significant 28% reduction in all-cause mortality.

Patients in the radial access arm (n = 4197) had fewer major adverse cardiovascular events (8.8%) than the 4207 patients who were assigned to transfemoral access, among whom 10.3% had a major cardiovascular event. The difference failed to meet the prespecified value for superiority. The rate of major bleeding was 1.6% in the transradial arm versus 2.3% in the transfemoral group (relative risk [RR],0.67; 95% CI, 0.49-0.92; P = .013) and all-cause mortality was 1.6% versus 2.2% (RR, 0.72; 95% CI, 0.53-0.99; P = .045), favoring transradial access.

The trial included experienced operators, enrolling interventional cardiologists who performed at least 75 transradial coronary interventions within the past year, at least 50% of which were done via the radial artery. The benefit was most pronounced among the highest-volume radial PCI centers (>80% PCIs by radial access). This suggests that for catheterization laboratories that already have good outcomes with femoral access with low vascular complication rates, benefit from radial access may be minimal.

The MATRIX study was published in The Lancet on March 16, 2015.

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CoreValve Shows Superiority in High-Risk Patients

Two-year results from the CoreValve High-Risk Study confirm 1-year data, according to new data presented at ACC 2015, which showed a significantly lower rate of death from all causes at 2 years compared with surgical valve replacement in patients with symptomatic aortic stenosis at increased risk for surgery.

Michael Reardon, MD, of the Houston Methodist Hospital System, said the new data show that the 1-year survival advantage was durable, sustainable, and actually widening out. The study, sponsored by Medtronic, included 795 patients randomized at one of 45 US centers to either surgical valve replacement or the CoreValve transcatheter valve.

At 2 years, the mortality rate among patients randomized to surgical aortic-valve replacement was 28.6%; among the transcatheter aortic-valve replacement (TAVR) patients, the mortality rate was 22.2%, a statistically significant difference. Stroke rates were also significantly lower with TAVR (10.9% with TAVR versus 16.6% with surgically treated patients).

Rates of major stroke were not statistically different between the 2 treatment arms at 2 years; stroke rates of 9.8% and 6.8% in the surgical and TAVR arms, respectively (P = .25). A total of 1.3% of patients had severe aortic regurgitation at 2 years and 5.2% had moderate aortic regurgitation. There were no findings of structural valve deterioration evident at 2 years.

Dr Reardon believes TAVR, with its self-expanding valve, should be considered preferred therapy, not just a reasonable alternative, for symptomatic patients at high risk for surgery.

The CoreValve is currently approved for use in patients with symptomatic aortic stenosis considered high risk for aortic valve replacement surgery and for patients considered inoperable.

The abstract of this study can be found online. Disclosures are provided in the abstract.

Dr Reardon serves on a Medtronic advisory board.