Resumption of Direct Oral Anticoagulants After Gastrointestinal Bleeding in Atrial Fibrillation: A Systematic Review of Timing and Clinical Outcomes.

Gastrointestinal bleeding (GIB) during direct oral anticoagulant (DOAC) therapy poses a clinical dilemma in atrial fibrillation (AF): stopping anticoagulation withdraws stroke protection, while restarting risks hemorrhage. No randomized trials exist, and current AF guidelines offer no fixed restart interval. This review synthesized observational evidence on DOAC resumption timing after GIB in adults with AF. Six databases were searched (MEDLINE, PubMed, Scopus, Google Scholar, ScienceDirect, and MDPI; January 2015 to April 2026) following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. Rayyan AI supported deduplication and screening. Risk of bias was assessed using Assessment of Multiple Systematic Reviews 2 (AMSTAR-2), Risk of Bias in Non-randomized Studies of Interventions version 2 (ROBINS-I V2), and the Joanna Briggs Institute (JBI) case report checklist. The outcomes were recurrent GIB, thromboembolic events, and all-cause mortality. Heterogeneity precluded meta-analysis; findings were synthesized narratively. Ten studies (2018-2025; 68,611 patients with AF across all included cohorts) included two systematic reviews and meta-analyses and eight primary studies. Resumption intervals ranged from under seven days to several months. At the drug-class level, DOAC resumption was not significantly associated with higher recurrent GIB risk in either pooled analysis (odds ratio (OR) 1.09, 95% confidence interval (CI) 0.77-1.53; hazard ratio (HR) 1.22, 95% CI 0.88-1.71); rivaroxaban was the only agent with a significantly elevated rebleeding hazard (HR 1.67, 95% CI 1.16-2.65). Thromboembolic events were 44% to 66% lower among resumers in the two largest cohorts. All-cause mortality was 46 to 50% lower in adjusted models, with comparable reductions in a network meta-analysis of 59,244 patients. The strongest predictor of recurrent hemorrhage was prior GIB; renal impairment and concurrent antiplatelet therapy also raised the risk. DOAC resumption after GIB in AF was consistently associated with lower thromboembolism and mortality, with no class-level increase in recurrent bleeding. Direct comparisons of resumption timing were too few to identify an optimal window, so the evidence bore more on whether to resume than on when. Rivaroxaban carried the one clear excess rebleeding signal, favoring apixaban after prior GIB. Individualized risk assessment should guide decisions pending trial data.