Dual antiplatelet therapy beyond one year after placement of a drug-eluting stent compared with aspirin therapy alone has been found to significantly reduce the risks of stent thrombosis and major adverse cardiovascular and cerebrovascular events despite being associated with an increased risk of bleeding and mortality, according to results of the DAPT trial presented Nov. 16 at AHA 2014 and simultaneously published in The New England Journal of Medicine.

Typically, dual antiplatelet therapy is recommended by physicians after coronary stenting to prevent thrombotic complications. However, the benefits and risks of this treatment beyond one year have remained uncertain. Investigating this particular time threshold, Laura Mauri, MD, MSc, FACC, an interventional cardiologist at Brigham and Women’s Hospital, and an associate professor of medicine at Harvard Medical School and Chief Scientific Adviser at the Harvard Clinical Research Institute in Boston, MA, and her co-authors enrolled a total of 9,961 patients after they had undergone a coronary stent procedure in which a drug-eluting stent was placed, treating them with thienopyridine drug (clopidogrel or prasugrel) and aspirin. After 12 months patients were randomly assigned to continue the thienopyridine treatment or receive a placebo.

Results of the investigation showed that for those who continued treatment with thienopyridine, as compared with the placebo, reduced rates occurred in stent thrombosis (0.4 percent vs. 1.4 percent; hazard ratio, 0.29 [95 percent confidence interval [CI]; 0.17 to 0.48]; P<0.001) and major adverse cardiovascular and cerebrovascular events (4.3 percent vs. 5.9 percent; hazard ratio, 0.71 [95 percent CI, 0.59 to 0.85]; P<0.001). The rate of myocardial infarction also registered lower with thienopyridine treatment than with placebo (2.1 percent vs. 4.1 percent; hazard ratio, 0.47; P<0.001). However, the rate of mortality from any cause was 2.0 percent in the thienopyridine treatment group, and 1.5 percent in the placebo group (hazard ratio, 1.36 [95 percent CI, 1.00 to 1.85] p=0.05). Data also showed that the rate of moderate or severe bleeding was increased with continued thienopyridine treatment (2.5 percent vs. 1.6 percent, P=0.001). During the three months after discontinuation of thienopyridine treatment, an elevated risk of stent thrombosis and myocardial infarction was observed in both groups.

“The DAPT Study was the first and only study comparing durations of treatment with antiplatelet therapy that was adequately powered to detect a benefit on stent-related heart attacks,” said Mauri.

Prevention of heart attack and blood clots in stents with longer antiplatelet therapy was consistent in all patient groups, drug and stent types studied, Mauri noted, but “physicians should consider individual patient risks in prescribing dual anti-clotting therapy. In particular, the trial excluded patients with a history of major bleeding either before the stent procedure or within the first year of treatment.”

Antonio Colombo, MD, FACC, and Alaide Cheiffo, MD, note in an editorial comment that “they key message of the DAPT study is the suggestion that some patients who have been treated with a drug-eluding stent may benefit from extending dual antiplatelet therapy beyond one year, but also that the potential harm with this approach should not be overlooked.” They add that “we do not know how long this benefit extends and which patients benefit most. The safest and most effective duration of dual antiplatelet therapy therefore remains uncertain and must be individualized for each patient; presumably in making this judgment, physicians should balance risk factors favoring atherothrombosis against the risk of bleeding.”

In a statement released Nov. 16, the U.S. Food and Drug Administration said it is evaluating the preliminary data from the trial, but believes the benefits of clopidogrel and prasugrel therapy continue to outweigh their potential risks when used for approved uses. The agency said “health care professionals should not change the way they prescribe these drugs at this time” and advised patients to “not stop taking these drugs because doing so may result in an increased risk of heart attacks, blood clots, strokes, and other major cardiovascular problems.”

Keywords: Myocardial Infarction, Stroke, United States Food and Drug Administration, Thrombosis, Drug-Eluting Stents, Boston, Ticlopidine, Piperazines, Confidence Intervals, Aspirin, Risk Assessment, AHA Annual Scientific Sessions