Continuing dual antiplatelet therapy (DAPT) beyond one year reduced the risk of ischemic events in patients treated with drug-eluting stents, but at the cost of an increased bleeding risk, the DAPT study group reported Nov. 16 at the American Heart Association scientific session in Chicago.
The DAPT (Dual Antiplatelet Therapy) study was requested by the FDA in an attempt to resolve questions about the optimal duration of thienopyridine therapy, whether clopidogrel (Plavix, Bristol-Myers Squibb/Sanofi-Aventis) or prasugrel (Effient, Daiichi Sankyo), plus aspirin to reduce the risk of stent thrombosis after implantation of drug-eluting stents. The international, randomized, placebo-controlled study enrolled patients between 2009 and 2011 through either the Harvard Clinical Research Institute or one of four postmarketing surveillance studies involving four different drug-eluting stents.
After 12 months of DAPT, patients who were adherent to their therapy and who had no major adverse cardiovascular or cerebrovascular events, repeat revascularization, or moderate or severe bleeding became eligible for the study. Those 9,961 patients were randomized to receive aspirin and thienopyridine therapy or aspirin and placebo for 18 months. At that point, patients took aspirin only and were observed for an additional three months.
The primary efficacy endpoints were the cumulative incidence of definite or probable stent thrombosis and of major adverse cardiovascular or cerebrovascular events in the randomization study period. The researchers designed this as a superiority analysis.
The primary safety endpoint was the incidence of moderate or severe bleeding during the randomization study period. This was designed as a noninferiority analysis.
The thienopyridine group had a lower cumulative rate of stent thrombosis compared with placebo (0.4 percent vs. 1.4 percent); of major adverse cardiovascular or cerebrovascular events (4.3 percent vs. 5.9 percent); and of MI (2.1 percent vs. 4.1 percent). The rate of moderate or severe bleeding was higher in the thienopyridine group (2.5 percent vs. 1.6 percent).
The rates of death by either cardiac or vascular causes was similar between the groups but all-cause mortality was higher in the thienopyridine group (2 percent vs. 1.5 percent). In an analysis that included the three-month observation period when patients received only aspirin, the DAPT researchers found a higher death rate from noncardiovascular causes in the thienopyridine group. They determined that that group also had a higher number of cancer-related deaths; mortality was no longer significantly different once they excluded those patients.
In a statement released Nov. 16, the FDA supported the use of DAPT based on trial results. "FDA believes the benefits of clopidogrel (Plavix) and prasugrel (Effient) therapy continue to outweigh their potential risks when used for approved uses," it wrote.
The DAPT study was published online in the New England Journal of Medicine simultaneously with the presentation by principal investigator and lead author Laura Mauri, MD, of Brigham and Women’s Hospital in Boston.