Antiplatelet Therapy in Patients with Atrial Fibrillation: A Systematic Review and Metaanalysis of Randomized Trials.

AIMS: To systematically assess the effects of antiplatelets on clinical outcomes in patients with atrial fibrillation (AF), treated and not treated with oral anticoagulation. METHODS AND RESULTS: We searched MEDLINE, Embase and CENTRAL from inception until September 2020. From 5,446 citations, we selected randomized trials allocating patients with AF to antiplatelet therapy vs. control. We applied random-effects models for meta-analysis and assessed potential effect modification with background anticoagulation use. Eighteen trials including 21,518 participants met our prespecified eligibility criteria. In 10 studies without background anticoagulation, antiplatelets reduced all-cause stroke (486/6,165 [events/patients] vs. 621/6,061; risk ratio [RR] 0.77, 95% confidence interval [CI] 0.69-0.86, I2=0%). In 8 studies with background anticoagulation, there was a signal for an increase in all-cause stroke with antiplatelets (97/4,608 vs. 72/4,684; RR 1.33, 95% CI 0.98-1.79, I2=0%), p-value for interaction < 0.001. A similar pattern emerged for ischaemic stroke. Irrespective of background anticoagulation use, antiplatelets increased major bleeding (509/10,402 vs. 328/10,496; RR 1.54, 95% CI 1.35-1.77, I2=0%) and intracranial Haemorrhage (107/10,221 vs. 65/10,232; RR 1.64, 95% CI 1.20-2.24, I2=0%), and reduced myocardial infarction (201/9,679 vs. 260/9,751; RR 0.79, 95% CI 0.65-0.94, I2=0%), all p-values for interaction ≥ 0.36. Antiplatelets did not affect mortality (1,221/10,299 vs. 1,211/10,287; RR 1.02, 95% CI 0.89-1.17, I2=29%), p-value for interaction = 0.23. CONCLUSIONS: In patients with AF not receiving oral anticoagulation, antiplatelet therapy modestly reduced stroke. There was a corresponding signal for harm when used on top of anticoagulation. Irrespective of background anticoagulation use, antiplatelet therapy significantly increased bleeding, moderately reduced myocardial infarction and did not affect mortality.