Varespladib significantly increased heart attack risk in patients with acute coronary syndrome (ACS) in a trial that terminated early due to futility and potential harm. The study findings were published online Nov. 18 in JAMA and presented simultaneously at the American Heart Association’s scientific session.
The Vascular Inflammation Suppression to Treat Acute Coronary Syndromes for 16 Weeks (VISTA-16) study attempted to determine the effects of varespladib, a secretory phospholipase A2 (sPLA2), on the risk of cardiovascular disease in patients with ACS. Researchers randomized 5,145 eligible patients at 362 hospitals throughout Europe, Australia, New Zealand and North America to receive either 500 mg of varespladib or a placebo for 16 weeks between June 2010 and March 2012, when the study was terminated.
The primary outcome was a composite of cardiovascular mortality, nonfatal MI, nonfatal stroke or ischemic unstable angina that required hospitalization after the 16-week period.
The primary endpoint occurred in a higher percentage of participants in the varespladib group compared to placebo (6.1 percent vs. 5.1 percent), due mostly to a higher percentage of heart attacks (3.4 percent vs. 2.2 percent). Six months after the study was terminated, death from any cause was higher in the varespladib group (2.7 percent vs. 2 percent) among participants whose survival status was determined.
Adverse effects occurred in 2.8 percent of the experimental group compared with 1.4 percent of the placebo group.
“Despite experimental and observational clinical data suggesting that pan-inhibition of sPLA2 would exert beneficial cardiovascular effect, the VISTA-16 trial provides evidence to the contrary,” wrote the investigators, led by Stephen J. Nicholls, MBBS, PhD, of the South Australian Health and Medical Research Institute and the University of Adelaide in Adelaide, Australia.
While the mechanism behind the potentially harmful risk profile of varespladib has not been determined, Nicholls and colleagues argued that the drug “may be harmful and is not a useful strategy to reduce adverse cardiovascular outcomes after ACS.”
Anthera Pharmaceuticals funded the study.