October 21st, 2013
Refining the Optimal Duration of Dual Antiplatelet Therapy After DES Implantation
CardioExchange’s Harlan Krumholz interviews Cheol Whan Lee and Seung-Jung Park about their study group’s randomized trial comparing dual antiplatelet therapy with aspirin alone beyond 12 months after drug-eluting stent implantation. The findings are published in Circulation.
At 24 centers in South Korea, 5045 patients who received a drug-eluting stent (DES) and were free of major adverse cardiovascular events and major bleeding for at least 12 months after the procedure were randomly assigned, in open-label fashion, to receive aspirin alone or to continue clopidogrel plus aspirin. Incidence of the primary endpoint — a composite of death from cardiac causes, myocardial infarction, or stroke at 24 months after randomization — was similar in the two groups (aspirin alone, 2.4%; dual therapy, 2.6% (hazard ratio, 0.94; 95% CI, 0.66–1.35; P=0.75), as were the individual risks for all-cause mortality, MI, stent thrombosis, and stroke. The incidence of major bleeding was 1.1% in the aspirin-alone group and 1.4% in the dual-therapy group, (HR, 0.71; 95% CI, 0.42–1.20; P=0.20).
Krumholz: In your study, the benefit of extending dual antiplatelet therapy beyond 12 months was similar to that of aspirin alone. What is the usual practice in South Korea?
Lee and Park: Dual antiplatelet therapy (DAPT) for 6 to 12 months after DES implantation is usual practice in Korea. Beyond 6 to 12 months after DES implantation, most doctors discontinue DAPT and use either aspirin or clopidogrel alone.
Krumholz: In a previous study of yours, you found a similar result. Why was it necessary to do this study?
Lee and Park: As we describe in our introduction, the long-term dual-therapy arm in the first study was associated with a trend toward increased risk for cardiac death and myocardial infarction. We did the second study to confirm this observation.
Krumholz: Your confidence intervals are quite wide. You cannot exclude a benefit of as much as a 34% lower risk. Given that lower limit, do you feel confident that you can really exclude a benefit of longer DAPT?
Lee and Park: We agree. To narrow the confidence interval, we would need a much larger study. However, this is now difficult because 6 to 12 months of DAPT is usual practice in the era of new DES.
Krumholz: You powered the study for a 50% reduction. On what basis did you identify that as the right effect size to detect? Wouldn’t people care about a smaller effect than that?
Lee and Park: We agree. The sample size was based on the first study’s findings. As you know, this kind of study is difficult to conduct because of low patient participation and poor compliance.
Krumholz: What is the next study that should be done in this area?
Lee and Park: DES technology has improved greatly during the past decade. New DES seems to be safer than bare-metal stents, and stent thrombosis mostly occurs within 3 months after new DES implantation. Therefore, we think that the duration of DAPT can be further shortened in the era of new DES, a topic for the next study.
JOIN THE DISCUSSION
What effect will the trial conducted by Dr. Lee and Dr. Park have on your practice and on the direction of research on dual antiplatelet therapy after drug-eluting stent implantation?