Background Dual antiplatelet therapy is preferred following coronary stenting to avoid thrombotic complications yet the benefits and risks of treatment beyond 1 year are uncertain. P<0.001) and major adverse cardiovascular and cerebrovascular events (4.3% vs. 5.9% hazard ratio 0.71 95 CI 0.59-0.85 P<0.001). Myocardial infarction was reduced (2.1% vs. 4.1% risk percentage 0.47 P<0.001). Rates of all-cause mortality in the continued thienopyridine and placebo organizations were 2.0 and 1.5% respectively (hazard ratio 1.36 95 CI 1.00-1.85 P=0.052). Moderate or severe bleeding was improved with continued thienopyridine (2.5% vs. 1.6% P=0.001). An elevated risk for stent thrombosis and myocardial infarction SRT1720 was observed in both organizations during the 3 months following thienopyridine discontinuation. Summary Dual antiplatelet therapy beyond one year after drug-eluting stent placement significantly reduced the risks of stent thrombosis and major adverse cardiovascular and cerebrovascular events compared with aspirin only but was associated with improved bleeding. Intro Millions of individuals worldwide receive coronary stents each year for the treatment of ischemic heart disease.1 2 Although drug-eluting stents reduce restenosis compared with bare metallic stents there is concern that drug-eluting stents may be associated with risks of stent thrombosis occurring beyond one year after treatment.3 Stent thrombosis while rare is frequently associated with myocardial infarction and may be fatal.3 Furthermore ischemic events such as myocardial infarction stroke or cardiovascular death unrelated to the treated coronary lesion also happen beyond one year.4 5 The use of dual antiplatelet therapy combining a P2Y12 receptor inhibitor with aspirin is critically important to prevent coronary stent thrombosis and is currently recommended for 6 to 12 months after implantation of a drug-eluting stent.6 7 While some observational SRT1720 studies suggest that extending dual antiplatelet therapy beyond one year is associated with a lower risk of myocardial infarction following drug-eluting stent treatment8 several tests have also demonstrated increased risk of bleeding without lowering myocardial infarction incidence with longer therapy.9-12 Whether treatment with dual antiplatelet therapy beyond one year reduces either SRT1720 coronary stent thrombosis or ischemic events remote to the stent has not been determined by an adequately powered randomized trial. The Dual Antiplatelet Therapy (DAPT) Study was an international multicenter randomized placebo-controlled trial to determine the benefits and risks of continuing SRT1720 dual antiplatelet therapy beyond one Rabbit Polyclonal to GPR116. year after treatment with coronary stents. Methods Study Design The DAPT Study design has been explained previously.13 The trial was designed SRT1720 in response to a request from the United States Food and Drug Administration (FDA) to manufacturers of coronary stents and was conducted under an investigational-device exemption via a public-private collaboration involving the FDA eight funding stent and pharmaceutical manufacturers (see Supplementary Appendix) and Harvard Clinical Study Institute (HCRI). The stent manufacturers who contributed to the funding of the trial experienced contributing functions in trial design and in data collection as detailed in the Supplementary Appendix. HCRI was responsible for the scientific conduct and independent analysis of the trial. A single standard randomized trial was designed incorporating five individual component studies to facilitate enrollment (Supplementary Appendix). Subjects were enrolled into the trial either by HCRI or from one of four post-marketing monitoring studies designed to collect similar SRT1720 medical data in related patient populations. Each contributing study followed standard randomization criteria and follow-up as specified by the overall DAPT Study protocol. A single medical events committee blinded to the randomized treatment task adjudicated events and an unblinded self-employed central data monitoring committee oversaw the security of all subjects. All participating organizations received institutional review table approval. The first three authors and the last author who published the manuscript under the coordination of HCRI experienced full access to the data; they vouch for the integrity of the analyses offered and for the fidelity of this report to the trial protocol which is available with the full text of this article at NEJM.org. The manuscript was offered to the funding manufacturers for review in advance of publication; however they did not possess the right of refusal except with regard to individual manufacturer.