Last month, the American Heart Association (AHA) held its annual Scientific Sessions meeting in Chicago, IL, featuring the latest advances in cardiovascular science. At several of the sessions, BWH clinicians, researchers and discoveries took center stage.

The President speaks

Elliott Antman

Elliott Antman, MD, FAHA, a senior physician in BWH’s Cardiovascular Division, is the current president of the AHA. At the meeting, he delivered his Presidential Address, “Saving and Improving Lives in the Information Age.” One of the overarching themes of his talk was the need to harness the latest technologies and data to drive innovation in clinical care.

Antman is an expert in atrial fibrillation, a type of abnormal heart rhythm that can lead to stroke, and the use of anticoagulant drugs to lower the risk of stroke. He recounted the history of these drugs, including warfarin, which was discovered serendipitously more than 50 years ago, as well as newer drugs, which have been both expensive and time-consuming to develop. “Obviously, we can’t rely on either method to find effective new therapies,” he said.

In addition to sharing his perspectives on the continuing need for innovation, Antman also unveiled a major new initiative — the first crop of researchers to win funding for the Cardiovascular Genome-Phenome Study (CVGPS). This effort leverages the massive amount of data from various studies, including the Framingham Heart Study and the Jackson Heart Study, as well as new patient cohorts, to accelerate the discovery of more personalized treatment and prevention for cardiovascular diseases and stroke. Among the winners was BWH’s Susan Cheng, MD, who will focus on chronic inflammation, cardiovascular aging and longevity.

Proof comes with IMPROVE-IT

Laura Mauri

One of the most highly anticipated studies to make a showing at the meeting was the IMProved Reduction of Outcomes: Vytorin Efficacy International Trial (IMPROVE-IT). The study, co-led by researchers at BWH and Duke Medicine, set out to answer some long-standing questions about cholesterol levels and heart disease — namely, does lowering cholesterol levels, beyond what can be achieved with a statin alone, result in improved outcomes for patients?

In this multicenter international randomized trial, researchers compared two approaches: statin (simvastatin) and placebo or statin with ezetimibe, which works differently from statins to lower LDL levels. They found that adding ezetimibe reduced the risk of heart attack and stroke in high-risk patients with pre-existing heart disease.

The researchers enrolled 18,144 patients with acute coronary syndrome (ACS), described as heart attacks or worsening chest pain, and all were treated according to the previously existing guidelines with a statin (simvastatin).

In the control group, patients who received statin therapy alone reached a median LDL cholesterol level of 69 mg/dl for a median of six years. Researchers found that when patients received the non-statin medication ezetimibe, in addition to the statin (ezetimibe/simvastatin combination/brand name VYTORIN) LDL cholesterol was reduced 20 percent further to a median level of 54 mg/dl, and this led to a statistically significant 6.4 percent reduction in the number of cardiovascular events.

“There is a lot of evidence that demonstrates that low cholesterol is better, and our findings suggest that even lower is even better,” said Christopher Cannon, MD, principal investigator of IMPROVE-IT and a cardiologist and researcher in the TIMI Study Group at BWH. “More broadly, the results of IMPROVE-IT re-emphasize the central role of lowering LDL cholesterol for the treatment of high risk patients.”

Eugene Braunwald, MD, founding TIMI chairman and former BWH physician-in-chief, is co-chair of the study.

Stents and length of anti-clotting therapy

A major international public health study exploring the prolonged use of anti-clotting drugs in 25,682 patients receiving coronary stents and randomizing over 11,000 patients reported that longer treatment—more than one year—is better. The Dual Antiplatelet Therapy Study (DAPT Study), led by principal investigator Laura Mauri, MD, MSc, of the Cardiovascular Division, and conducted in collaboration with the FDA, eight drug and device manufacturers and the Harvard Clinical Research Institute, found that patients who continued to take aspirin and either the drug clopidogrel (Plavix) or prasugrel (Effient) beyond the first year after stent placement had a lower risk of a new heart attack and a lower risk of developing blood clots within their stents, compared with patients who took both drugs for 12 months but continued on aspirin alone.

The study also shed light on the lingering question of whether bare-metal stents (BMS) were safer than drug-eluting stents (DES). Patients who were treated with DES had significantly lower risk of developing blood clots within their stents. The DAPT Study was the first clinical study powered to detect a benefit regarding this risk.

“Before this study, patients and physicians were not certain about whether longer treatment would be beneficial. In our study, patients who tolerated one year of treatment without major bleeding had half the risk of heart attack if they continued dual antiplatelet therapy beyond one year, a benefit that was larger than we had anticipated,” noted Mauri. “These findings show the preventive benefit of these medications in patients with coronary artery disease.”

Role of blood-thinning drug

Researchers from BWH and pharmaceutical company Boehringer Ingelheim also presented interim findings of a retrospective analysis of more than 38,000 patients with non-valvular atrial fibrillation (NVAF), a type of abnormal heart rhythm that can lead to stroke. The work, led by BWH’s John Seeger, PharmD, DrPH, examined the safety and effectiveness of dabigatran etexilate mesylate (Pradaxa) versus warfarin treatment among patients with NVAF treated as part of routine care. Interim findings suggest a 25 percent reduction in the rate of major hemorrhage (hazard ratio [HR] 0.75, 95 percent confidence interval [CI] 0.65-0.87, 354 vs. 395 events) and a 23 percent reduction in strokes (HR 0.77, CI 0.54-1.09, 62 vs 69 events) for dabigatran compared to warfarin. These findings that patients treated with Pradaxa had reduced instances of stroke and major bleeding events should be encouraging to patients and prescribers that dabigatran may represent a suitable alternative to warfarin.

TOPCAT results

BWH’s Marc Pfeffer, MD, PhD, of the Cardiovascular Division, presented his findings of regional variation in patients and outcomes in the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) Trial. When dividing data by regions, Pfeffer and his team found profound differences between the clinical outcomes of patients who received the drug Spironolactone in the Americas and those who received it in Georgia and Russia, with patients in the Americas showing a reduction in cardiovascular death and hospitalizations. Barring any other options for these patients, the data provide both clinicians and patients with evidence of the potential benefit of this therapy.