Three vs Twelve Months of Dual Antiplatelet Therapy After Zotarolimus-Eluting Stents

IMPORTANCE: The current recommendation is for at least 12 months of dual antiplatelet therapy after implantation of a drug-eluting stent. However, the optimal duration of dual antiplatelet therapy with specific types of drug-eluting stents remains unknown. OBJECTIVE: To assess the clinical noninferiority of 3 months (short-term) vs 12 months (long-term) of dual antiplatelet therapy in patients undergoing percutaneous coronary intervention (PCI) with zotarolimus-eluting stents. DESIGN, SETTING, AND PATIENTS: The OPTIMIZE trial was an open-label, active-controlled, 1:1 randomized noninferiority study including 3119 patients in 33 sites in Brazil between April 2010 and March 2012. Clinical follow-up was performed at 1, 3, 6, and 12 months. Eligible patients were those with stable coronary artery disease or history of low-risk acute coronary syndrome (ACS) undergoing PCI with zotarolimus-eluting stents. INTERVENTIONS: After PCI with zotarolimus-eluting stents, patients were prescribed aspirin (100-200 mg daily) and clopidogrel (75 mg daily) for 3 months (n = 1563) or 12 months (n = 1556), unless contraindicated because of occurrence of an end point. MAIN OUTCOMES AND MEASURES: The primary end point was net adverse clinical and cerebral events (NACCE; a composite of all-cause death, myocardial infarction MI, stroke, or major bleeding); the expected event rate at 1 year was 9%, with a noninferiority margin of 2.7%. Secondary end points were major adverse cardiac events (MACE; a composite of all-cause death, MI, emergent coronary artery bypass graft surgery, or target lesion revascularization) and Academic Research Consortium definite or probable stent thrombosis. RESULTS: NACCE occurred in 93 patients receiving short-term and 90 patients receiving long-term therapy (6.0% vs 5.8%, respectively; risk difference, 0.17 95% CI, -1.52 to 1.86; P = .002 for noninferiority). Kaplan-Meier estimates demonstrated MACE rates at 1 year of 8.3% (128) in the short-term group and 7.4% (114) in the long-term group (HR, 1.12 95% CI, 0.87-1.45). Between 91 and 360 days, no statistically significant association was observed for NACCE (39 2.6% vs 38 2.6% for the short- and long-term groups, respectively; HR, 1.03 95% CI, 0.66-1.60), MACE (78 5.3% vs 64 4.3%; HR, 1.22 95% CI, 0.88-1.70), or stent thrombosis (4 0.3% vs 1 0.1%; HR, 3.97 95% CI, 0.44-35.49). CONCLUSIONS AND RELEVANCE: In patients with stable coronary artery disease or low-risk ACS treated with zotarolimus-eluting stents, 3 months of dual antiplatelet therapy was noninferior to 12 months for NACCE, without significantly increasing the risk of stent thrombosis. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01113372.