Short-term dual antiplatelet therapy noninferior to long-term after drug-eluting stent placement

Three months of dual antiplatelet therapy after placement of a drug-eluting stent was noninferior to 12 months of therapy, according to a new study.

The OPTIMIZE trial, a randomized, open-label, active-controlled noninferiority study performed at 33 sites in Brazil, involved patients with stable coronary artery disease or a history of low-risk acute coronary syndrome who were undergoing percutaneous coronary intervention with a drug-eluting stent. After the procedure, patients were randomly assigned to receive aspirin, 100 to 200 mg/d, and clopidogrel, 75 mg/d, for 3 months or 12 months.

The study's primary end point was net adverse clinical and cerebral events (NACCE), defined as a composite of all-cause death, myocardial infarction (MI), stroke or major bleeding. The secondary end points were major adverse cardiac events, or MACE (defined as a composite of all-cause death, MI, emergent coronary artery bypass graft surgery, or target lesion revascularization), and definite or probable stent thrombosis as defined by the Academic Research Consortium. Study results were published online Oct. 31 by the Journal of the American Medical Association.

Between April 2010 and March 2012, 1,563 patients were assigned to short-term dual antiplatelet therapy and 1,556 were assigned to long-term therapy. Thirty-seven percent of patients were women; mean age was 61.3 years in the short-term group and 61.9 years in the long-term group. Clinical follow-up was performed at 1, 2, 6 and 12 months, and 76 patients declined or were lost to follow-up. Most patients received zotarolimus-eluting stents.

Overall, 93 patients in the short-term group and 90 patients in the long-term group had NACCE (6.0% vs. 5.8%, respectively; risk difference, 0.17; 95% CI, −1.52 to 1.86; P=0.002 for noninferiority). At 1 year, 8.3% of patients in the short-term group and 7.4% of patients in the long-term group developed MACE (hazard ratio, 1.12; 95% CI, 0.87 to 1.45). Between 91 and 360 days, no statistically significant association was seen between duration of therapy and NACCE, MACE, or stent thrombosis.

The researchers concluded that in patients undergoing percutaneous coronary intervention with zotarolimus-eluting stents, short-term dual antiplatelet therapy was noninferior to longer dual antiplatelet therapy for death, MI, stroke and major bleeding and did not increase stent thrombosis risk. However, they noted that second-generation drug-eluting stents show lower rates of stent thrombosis than first-generation stents, so it was not possible to determine whether all patients with drug-eluting stents could benefit from short-term dual antiplatelet therapy. Also, there were relatively low event rates observed, hinting that the study might not have been powered to detect small differences in ischemic and bleeding events after 90 days. The overall event rate for NACCE was 6% versus 9%, even though the rate of MACE was about 8%, which may have affected the statistical power to rule out a small degree of excess risk.

Another limitation included that the study population was mostly made up of patients with stable coronary artery disease or history of low-risk acute coronary syndrome. In addition, combining efficacy and safety within a single composite outcome might have masked important differences. Finally, randomization occurred at the time of the index procedure, which differs from clinical practice, when physicians and patients may need to decide on the duration of dual antiplatelet therapy before the decision to revascularize because it may be a factor in deciding whether to use a drug-eluting stent.