Experts provide in-depth analysis of key findings presented at AHA 2014

The American Heart Association Scientific Sessions in November featured the presentation of several major studies with practice-changing implications for the field of cardiology. After the conference, Cardiology Today and Healio.com/Cardiology asked leading experts to share their thoughts and perspective on trials including IMPROVE-IT, DAPT, WOSCOPS and more.

Robert A. Harrington, MD, chair of the 2014 AHA Scientific Sessions Program Committee, said this conference provided attendees with scientific data and discussion around “broad areas of science, from bench discovery science, through clinical and translational research, through population health and implementation science. “We can read about the science as it comes out or we can follow along with social media and traditional media, but nothing replaces face-to-face as a way to have a conversation, ask a question or probe data,” Harrington, the Arthur L. Bloomfield professor of medicine and chair of the department of medicine at Stanford University, told Cardiology Today.

Robert A. Harrington

IMPROVE-IT: Ezetimibe plus statin improved CV outcomes

For Patrick T. O’Gara, MD, FACC, results of the long-anticipated IMPROVE-IT trial of ezetimibe added to simvastatin (Vytorin, Merck) vs. simvastatin (Zocor, Merck) alone was the most important takeaway from AHA 2014.

“These results have re-engaged a conversation about guideline development for cholesterol-lowering in patients at risk, particularly in the high-risk population for whom secondary prevention would pertain," O'Gara, professor of medicine at Harvard Medical School and president of the American College of Cardiology, said. This study raises important questions about the current cholesterol guidelines and also “whether we need to go back and re-think whether targets for LDL reduction should be entertained,” he said.

Jason H. Wasfy, MD, co-chair of the Acute Myocardial Infarction Clinical Care Redesign Committee at Massachusetts General Hospital Institute for Heart, Vascular and Stroke Care, said there has been a trend toward statins as the “absolute backbone” cholesterol treatment, but the results of IMPROVE-IT “reopen the conversation about following LDL levels, and the potential for adjunctive anti-lipid therapies.”

Jason H. Wasfy

Reactions to IMPROVE-IT were mixed, however. Cardiology Today Editorial Board member Steven E. Nissen, MD, MACC, noted that while the observed improvement in clinical outcomes was statistically significant, it was small. “Essentially, it took 7 years of treatment with an expensive drug to reduce nonfatal events by 6.4%,” Nissen, chairman of the department of cardiovascular medicine at Cleveland Clinic, said in an interview.

He too said the impact of these results on prevention guidelines will be substantial.

DAPT: Longer-duration therapy decreased stent thrombosis and MACCE, increased bleeding

According to Wasfy, the assessment of dual antiplatelet therapy duration following cardiac stenting "is an enormous step forward and provides a lot of clarity on the issue." The results presented showing that DAPT reduced MI but increased bleeding risk "reinforces for clinicians that these decisions need to be customized based on risk profiles for individual patients. There is a trade-off between thrombosis and bleeding. ... The decision to prescribe DAPT for a certain length of time is ultimately about that trade-off."

O'Gara noted that the results presented at AHA 2014 on DAPT duration appear to contradict those from other smaller trials indicating that a duration as short as 6 months could be adequate in some cases. "These are really important results that will make all of us rethink the routine discontinuation of DAPT at various time points, as previously recommended, and I think will also re-engage the guideline-development process around recommendations in our literature about how long these drugs should be continued."

Patrick T. O'Gara

He added that, following the results from DAPT and related trials presented at AHA 2014, along with additional data that have become available since the guidelines had first been published, the ACC expects to reconvene with its partners and review the data to determine whether there may be grounds to change the existing guidelines.

"Collectively, these studies taught us that, among patients who undergo drug-eluting stenting and remain free from bleeding and ischemic events during the first year of therapy, an additional 18 months of DAPT significantly reduces the risk of stent thrombosis and atherothrombotic events, including those events unrelated to stent thrombosis," Herbert D. Aronow, MD, MPH, FACC, FSCAI, FSVM, governor of the Michigan chapter of the ACC and chair of the ACC Peripheral Vascular Disease section, told Cardiology Today.

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WOSCOPS: 20-year follow-up demonstrates clinical benefit of statins in men

Twenty-year follow up of a cohort of 6,595 middle-aged men assigned pravastatin from 1989 to 1995 demonstrated lower rates of mortality and CV events compared with men assigned placebo, regardless of whether they remained on statins after the study period, according to data from the WOSCOPS trial presented at AHA 2014.

Nissen said the persistent benefit observed in treated patients was a fascinating result. "For a lot of therapies, you only get the benefit while you are taking the drug. This study shows that lowering cholesterol effectively for 5 years with a relatively weak drug had a 20-year advantage for these patients. I think that is a blockbuster, and while it obviously has limitations it is important to understand the legacy benefits of statins."

Multiple STEMI analyses

Aronow also cited the AVOID and STEMI Accelerator trials as potentially practice-changing for STEMI care.

"The AVOID results called into question the time-honored tradition of administering supplemental oxygen, suggesting that oxygen therapy, when administered at levels higher than usual in the United States, was potentially harmful, leading to larger infarcts and more dysrhythmia," he told Cardiology Today.

The AVOID trial addressed a specific question of oxygen use in STEMI care, but also serves as a reminder that “we need to question, then test, even commonly considered concepts when they are not supported by evidence, Harrington said.

STEMI Accelerator indicated a link between longer delays in the ED and increased mortality. "STEMI times to treatment have decreased in recent years, but there is still much work to be done to harmonize these times with current guideline recommendations," Aronow said.

According to Harrington, the STEMI Accelerator data indicate that "systems of care really matter and are critical to improving outcomes."

FACTOR-64: CCTA screening for CAD failed to reduce 4-year events in diabetes patients

The FACTOR-64 trial assessed coronary CT angiography for the identification of CAD in asymptomatic patients with diabetes.

Steven E. Nissen

“Many of us, myself included, believe that screening asymptomatic patients is a very bad idea, and in fact this study showed no benefit whatsoever," Nissen said. "CT angiography is a technique that is widely used. … We probably need to stop people from having these screening tests done."

Studies indicate noninferiority of biodegradable polymer DES

Aronow cited the BASKET-PROVE II and EVOLVE II trials as presentations from AHA 2014 that might influence stent choice. In both trials, he said, biodegradable polymer DES were noninferior to permanent polymer DES with regard to cardiac death, MI or clinically driven target vessel revascularization. Aronow also noted that both stent types were more efficacious than bare-metal stents.

"On the flip side, cardiac death, MI and stent thrombosis occurred at similar rates across all three groups, suggesting there was no difference in safety, although these studies were underpowered in that respect," he said.

Aspirin failed to reduce events in older Japanese patients

In this study of 4,464 patients in Japan aged 60 to 85 years with CV risk factors, daily low-dose aspirin did not decrease long-term atherosclerotic events compared with no aspirin use.

"This speaks to something I feel very strongly about, which is that people who do not yet have heart disease should not take aspirin for prophylaxis," Nissen said. "I cannot tell you how many of my patients come in and believe that taking an aspirin a day is a good thing, particularly if you have high risk. This study shows that overall, the hazards [from daily low-dose aspirin] are about as great as the benefits. We need to get the message out to patients that taking aspirin [without] a prior MI, stroke or other evidence of active disease is not a good idea." – by Adam Taliercio

Disclosure: Nissen and O’Gara report no relevant financial disclosures. Aronow reports noncompensated professional society and clinical trial leadership positions. Wasfy reports paid consulting services for QPID Health and serving on the board of NCDR PINNACLE.