Optimal antithrombotic strategies in atrial fibrillation patients undergoing PCI: A network meta-analysis of randomized trials

Background: Optimal antithrombotic management for patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS) or coronary artery disease (CAD) remains challenging because bleeding and ischemic risks compete. We compared five strategies: de-escalation (short-course dual therapy followed by DOAC monotherapy), VKA triple therapy, VKA dual therapy, DOAC dual therapy, and DOAC triple therapy. Methods: We searched PubMed, Embase, Web of Science, Scopus, and CENTRAL from inception to 20 December 2025 for randomized controlled trials (RCTs). We performed a frequentist random-effects network meta-analysis (NMA) and reported risk ratios (RRs) with 95% confidence intervals (CIs). Treatments were ranked using P-scores. The primary outcomes were all-cause death and ISTH major or clinically relevant non-major bleeding. Results: Seven RCTs (12,469 participants) were included. For International Society on Thrombosis and Haemostasis (ISTH) major or clinically relevant non-major bleeding (CRNMB), de-escalation reduced bleeding compared with DOAC dual therapy (RR 0.50; 95% CI 0.30–0.82); this estimate is informed by a single Japanese trial (OPTIMA-AF) and should be interpreted cautiously. In contrast, VKA dual therapy (RR 1.33; 95% CI 1.02–1.72) and VKA triple therapy (RR 1.42; 95% CI 1.21–1.66) increased bleeding risk versus DOAC dual therapy; DOAC triple therapy did not differ significantly. There were no significant differences in all-cause death, myocardial infarction, or stent thrombosis among strategies. However, VKA triple therapy increased intracranial hemorrhage (RR 2.95; 95% CI 1.32–6.56) and VKA dual therapy increased stroke (RR 2.72; 95% CI 1.15–6.45) compared with DOAC dual therapy. Conclusions: In AF patients undergoing PCI, a strategy of short-course dual therapy followed by DOAC monotherapy may reduce bleeding compared with DOAC dual therapy, but evidence is limited and derives from one randomized trial. VKA-based regimens—particularly VKA triple therapy—consistently increased bleeding and intracranial hemorrhage. For ischemic outcomes, event rates were low and confidence intervals were wide; therefore, findings should be interpreted as no statistically detectable differences rather than equivalence.