Clopidogrel plus aspirin was inferior to oral anticoagulation for preventing vascular events in atrial fibrillation.

M e t h o d s Design: Randomized controlled trial (Atrial fibrillation Clopidogrel Trial with Irbesartan for prevention of Vascular Events [ACTIVE W]). Allocation: Concealed.* Blinding: Blinded (outcome assessors and monitoring committee).* Follow-up period: Median 1.28 years. Setting: 30 clinical centers worldwide. Patients: 6706 patients (mean age 70 y, 66% men) with AF and ≥ 1 of the following criteria: age ≥ 75 years; receiving treatment for systemic hypertension; previous stroke, transient ischemic attack, or non–central nervous system (non-CNS) systemic embolus; left ventricular dysfunction with left ventricular ejection fraction < 45%; peripheral arterial disease; or age 55 to 74 years with diabetes mellitus requiring drug therapy or previous coronary artery disease. Exclusion criteria were contraindication to clopidogrel or oral anticoagulant, documented peptic ulcer disease within the previous 6 months, previous intracerebral hemorrhage, significant thrombocytopenia, or mitral stenosis. Intervention: Clopidogrel, 75 mg/d plus aspirin, 75 to 100 mg/d (n = 3335), or oral anticoagulation (n = 3371). Patients in the oral anticoagulation group received a vitamin K antagonist and were monitored to keep the international normalized ratio (INR) between 2.0 and 3.0. The dose of oral anticoagulation was managed by study investigators or by local anticoagulation clinics. Outcomes: A composite endpoint of the first occurrence of stroke, non-CNS systemic embolism, myocardial infarction, or vascular death. Secondary outcomes included total stroke, total mortality, and hemorrhage. Patient follow-up: 99.7% (intention-to-treat analysis). M a i n r e s u l t s The trial stopped early (median 1.28 y) because clopidogrel plus aspirin was clearly inferior to oral anticoagulation therapy (Table). Clopidogrel plus aspirin also led to greater rates of total stroke and total hemorrhage (Table). Groups did not differ for total mortality and major hemorrhage (Table).