Walking a tightrope: the safety and efficacy of oral anticoagulants in atrial fibrillation patients with prior intracranial haemorrhage: a systematic review and meta-analysis

INTRODUCTION: The optimal anticoagulation strategy for patients with atrial fibrillation (AF) and prior intracranial haemorrhage (ICH) remains uncertain. Although direct oral anticoagulants (DOACs) have demonstrated a more favourable safety profile than vitamin K antagonists (VKAs) in the general AF population, comparative evidence in patients with previous ICH is limited. METHODS: We conducted a systematic review and meta-analysis comparing DOACs and VKAs in patients with AF and prior ICH. PubMed, Scopus and ScienceDirect were searched from inception to 16 March 2026. Outcomes of interest were ischaemic stroke, recurrent ICH and all-cause mortality. Risk of bias was assessed using Risk of Bias In Non-randomised Studies of Interventions (ROBINS-I) V.2. Pooled HRs with 95% CIs were calculated using random-effects models. RESULTS: Five observational studies were included. Compared with VKAs, DOACs were associated with a lower risk of recurrent ICH (5 studies, HR 0.65, 95% CI 0.53 to 0.79), ischaemic stroke (4 studies, HR 0.80, 95% CI 0.68 to 0.94) and all-cause mortality (3 studies, HR 0.64, 95% CI 0.45 to 0.89). Heterogeneity was absent for ischaemic stroke and recurrent ICH (I²=0%) but substantial for mortality (I²=89%). The recurrent ICH finding remained robust across leave-one-out, Hartung-Knapp-Sidik-Jonkman and overlap-adjusted sensitivity analyses, whereas the ischaemic stroke and mortality estimates lost statistical significance under more conservative methods. CONCLUSION: DOACs appeared favourable over VKAs for recurrent ICH, ischaemic stroke and mortality, but certainty of evidence ranged from moderate to very low. These findings are hypothesis-generating and should inform shared decision-making, not definitive practice change, pending randomised evidence. PROSPERO REGISTRATION NUMBER: CRD420261333839.