Antiplatelet therapy in patients with atrial fibrillation: a systematic review and meta-analysis of randomized trials

The aim of this study was to systematically assess the effects of antiplatelets on clinical outcomes in patients with atrial fibrillation (AF), treated and not-treated with oral anticoagulation.

We searched MEDLINE, Embase, and CENTRAL from inception until September 2020. From 5446 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 [486/6165 (events/patients) vs. 621/6061; risk ratio (RR) 0.77, 95% confidence interval (CI) 0.69–0.86, I² = 0%]. In eight studies with background anticoagulation, there was a signal for an increase in all-cause stroke with antiplatelets (97/4608 vs. 72/4684; 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 (201/9679 vs. 260/9751; RR 0.79, 95% CI 0.65–0.94, I² = 0%, all P-values for interaction ≥0.36). Antiplatelets did not affect mortality (1221/10 299 vs. 1211/10 287; RR 1.02, 95% CI 0.89–1.17, I² = 29%, P-value for interaction = 0.23).

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.