A systematic review of randomized trials comparing double versus triple antithrombotic therapy in patients with atrial fibrillation undergoing percutaneous coronary intervention

Background: Prior randomized controlled trials (RCT) evaluating the optimal antithrombotic therapies for patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI) have not been powered to evaluate ischemic outcomes. We compared double therapy with oral anticoagulation (OAC) and a P2Y12 inhibitor to triple therapy with an OAC + dual antiplatelet therapy in patients with AF requiring PCI. Methods: Using PRISMA guidelines, we searched for RCTs including patients with AF as an indication for OAC and undergoing PCI or medical management of acute coronary syndrome. The results were pooled using fixed-effects and random-effects models to estimate the overall effect of double therapy versus triple therapy on ischemic and bleeding outcomes. Results: We identified four RCTs, comprising 10,238 patients (5,498 double therapy, 4,740 triple therapy). Trial-reported major adverse cardiovascular events were similar between double therapy and triple therapy (fixed effect model OR 1.09, 95% CI 0.94–1.26). However, stent thrombosis (61/5,496 double therapy vs. 33/4738 triple therapy; fixed effect model OR 1.57, 95% CI 1.02–2.40; number needed to treat with triple therapy = 242) favored triple therapy. Bleeding outcomes were less frequent with double therapy (746/5470 vs. 950/4710; fixed effect model OR 0.59, 95% CI 0.53–0.65; number needed to harm with triple therapy = 16), but with significant heterogeneity (Q = 8.33, p =.04; I² = 64%), as were intracranial hemorrhages (19/5470 vs. 30/4710; fixed effect model OR 0.54, 95% CI 0.31–0.96). Conclusions: Double therapy in patients with AF requiring OAC following PCI or Acute coronary syndrome has a significantly better safety profile than triple therapy but may be associated with a modest increased risk of stent thrombosis.