Findings on Dual Antiplatelet Therapy

A new noninferiority study examining the duration of dual antiplatelet therapy for patients who received zotarolimus-eluting stents found that 3-months of dual antiplatelet therapy (DAPT) was noninferior to 12 months of therapy when evaluating a composite of death from any cause, myocardial infarction (MI), stroke, or major bleeding.

The results of the OPTIMIZE (Optimized Duration of Clopidogrel Therapy Following Treatment With the Zotarolimus-Eluting Stent in Real World Clinical Practice) trial were recently published online in Journal of the American Medical Association [DOI:10.1001/jama.2013.282183].

According to the authors of this randomized trial, current recommendations suggest DAPT for at least 12 months after the implementation of a drug-eluting stent. However, research has shown different safety profiles for stents based on generation and device. In addition, there has been limited research on the optimal duration of antiplatelet therapy for specific types of drug-eluting stents.

"What drove us to design and conduct the OPTIMIZE trial was the lack of robust and consistent data to sustain current guidelines for long-term (≥12 months) dual-antiplatelet therapy for patients undergoing second generation drug-eluting stents, given that such therapy has been associated with several drawbacks, including bleeding complications, compliance issues, and cost," said Fausto Feres, MD, PhD, a lead research in the study, during an interview with First Report Managed Care.

In this multicenter study, researchers investigated the difference duration of DAPT for patients who received zotarolimus-eluting stents—a second-generation drug-eluting stent—by randomly assigning 3119 patients in 33 sites to either receive 75 mg of clopidogrel daily for 3 months (short-term treatment) or 12 months (long-term treatment). Patients in both groups were also prescribed between 100 mg and 200 mg of aspirin daily.

Patients were included in the study if they had symptoms of either a stable angina or silent ischemia, or if they had low risk acute coronary syndrome due to an unstable angina or a recent nonacute MI.   Patients also needed to be undergoing percutaneous coronary intervention with zotarolimus-eluting stents. Patients with meeting these criteria were selected to join the study between April 2010 and March 2012.

Participants received clinical follow-up at 1, 3, 6, and 12 months to assess the implications of short-term versus long-term treatment regimens. 

Researchers identified the primary end point of the trial as net adverse clinical and cerebral events (NACCE), which was made up of a composite of death from any cause, MI, stroke, or major bleeding. The noninferiority fixed margin was 2.7%.

Major adverse cardiac events (MACE)—including death from any cause, MI, emergent coronary artery bypass graft surgery, or target-lesion revascularization—along with stent thrombosis and bleeding were a few of the secondary end points.

After analyzing the study's data, researchers found that the short-term therapy was noninferior to the long-term therapy group for the primary outcome. The primary outcome occurred in 93 patients in the 3-month group and 90 patients in the 12-month group (6% vs 5.8% based on cumulative incidence of events; risk difference, 0.17; 95% confidence interval [CI], -1.52-1.86; P=.002 for noninferiority). The rates of NACCE were similar between the groups between days 91 and 360 of the study.

The study also found that there were also no significant associations for MACE or stent thrombosis between 91 and 360 days of the study. Overall, the short-term group had a MACE rate at 1 year of 8.3%, while the long-term group had a rate of 7.4% (hazard ratio, 1.12; 95% CI, 0.87-1.45).

"There was no significant differences in the occurrence of MACE, a composite of death, MI, urgent coronary artery bypass graft surgery, or target lesion revascularization at 1-year follow-up," said Dr. Feres.

The researchers acknowledged study limitations. For instance, due to the low event rates observed, the study may not have been powered to detect small differences in ischemic and bleeding events. The overall NACCE event rates were lower than expected, which could impact the statistical power of the study.