Safety and efficacy of oral anticoagulation in patients with intracranial hemorrhage and atrial fibrillation: a systematic review and meta-analysis of randomized controlled clinical trials

Background: Patients with atrial fibrillation (AF) who survive spontaneous intracerebral hemorrhage (ICH) face competing risks of thromboembolism and recurrent bleeding. Objectives: To evaluate the safety and efficacy of initiating oral anticoagulants versus avoiding anticoagulation in adults with AF after spontaneous ICH. Design: Systematic review and meta-analysis of randomized-controlled clinical trials (RCTs). Data sources and methods: We searched MEDLINE, Scopus, and ClinicalTrials.gov up to August 28, 2025, for eligible RCTs randomizing adults with AF and prior spontaneous ICH to start oral anticoagulation versus avoid anticoagulation. Efficacy outcomes included the occurrence of new ischemic stroke (primary) and ischemic major adverse cardiovascular events (MACE; secondary). Safety outcomes included recurrent ICH (primary), hemorrhagic-MACE, all-cause mortality at follow-up, and cardiovascular death (secondary). Risk ratios (RRs) with 95% confidence intervals (CIs) were pooled using random-effects meta-analysis. Results: Six RCTs were included, comprising 403 patients in the anticoagulation group and 395 in the avoid-anticoagulation group. Anticoagulants reduced the rates of new ischemic stroke (RR = 0.20; 95% CI: 0.06–0.72; I 2 = 60%; number needed to treat = 9) and ischemic-MACE (RR = 0.41; 95% CI: 0.23–0.75; I 2 = 32%). Anticoagulants were associated with higher rates of recurrent ICH (RR = 3.14; 95% CI: 1.41–7.01; I 2 = 0%; number needed to harm = 19) and hemorrhagic-MACE (RR = 2.35; 95% CI: 1.32–4.21; I 2 = 1%). All-cause mortality at 90 days (RR = 1.06; 95% CI: 0.69–1.64; I 2 = 28%) and cardiovascular death (RR = 0.98; 95% CI: 0.34–2.87; I 2 = 63%) did not differ between the two groups. Leave-one-out sensitivity analyses supported the overall direction of effects, with some attenuation when individual trials were omitted. Conclusion: In AF survivors of spontaneous ICH, restarting oral anticoagulation lowers ischemic events but raises risks of recurrent ICH and major bleeding, without a clear early mortality difference. Potential benefits may outweigh risks in selected patients within a multidisciplinary framework. Adequately powered RCTs are needed to refine agent choice, timing, and patient selection. Trial registration: PROSPERO CRD420251135299 (registered August 27, 2025).