Oral anticoagulants versus antiplatelet therapy for preventing stroke in patients with non-valvular atrial fibrillation and no history of stroke or transient ischemic attacks

BACKGROUND: Non-valvular atrial fibrillation (AF) carries an increased risk of stroke mediated by embolism of stasis-precipitated thrombi originating in the left atrial appendage. Both oral anticoagulants and antiplatelet agents have proven effective for stroke prevention in most patients at high risk for vascular events, but primary stroke prevention in patients with non-valvular AF potentially merits separate consideration because of the suspected cardio-embolic mechanism of most strokes in AF patients. OBJECTIVES: To characterize the relative effect of long-term oral anticoagulant treatment compared with antiplatelet therapy on major vascular events in patients with non-valvular AF and no history of stroke or transient ischemic attack (TIA). SEARCH STRATEGY: We searched the Cochrane Stroke Group Trials Register (June 2006). We also searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 2, 2006), MEDLINE (1966 to June 2006) and EMBASE (1980 to June 2006). We contacted the Atrial Fibrillation Collaboration and experts working in the field to identify unpublished and ongoing trials. SELECTION CRITERIA: All unconfounded, randomized trials in which long-term (more than four weeks) adjusted-dose oral anticoagulant treatment was compared with antiplatelet therapy in patients with chronic non-valvular AF. DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials for inclusion, assessed quality and extracted data. The Peto method was used for combining odds ratios after assessing for heterogeneity. MAIN RESULTS: Eight randomized trials, including 9598 patients, tested adjusted-dose warfarin versus aspirin (in dosages ranging from 75 to 325 mg/day) in AF patients without prior stroke or TIA. The mean overall follow up was 1.9 years/participant. Oral anticoagulants were associated with lower risk of all stroke (odds ratio (OR) 0.68, 95% confidence interval (CI) 0.54 to 0.85), ischemic stroke (OR 0.53, 95% CI 0.41 to 0.68) and systemic emboli (OR 0.48, 95% CI 0.25 to 0.90). All disabling or fatal strokes (OR 0.71, 95% CI 0.59 to 1.04) and myocardial infarction (OR 0.69, 95% CI 0.47 to 1.01) were substantially but not significantly reduced by oral anticoagulants. Vascular death (OR 0.93, 95% CI 0.75 to 1.15) and all cause mortality (OR 0.99, 95% CI 0.83 to 1.18), were similar with these treatments. Intracranial hemorrhages (OR 1.98, 95% CI 1.20 to 3.28) were increased by oral anticoagulant therapy. AUTHORS' CONCLUSIONS: Adjusted-dose warfarin and related oral anticoagulants reduce stroke, disabling stroke and other major vascular events for those with non-valvular AF by about one third when compared with antiplatelet therapy.