Timing and Safety of Anticoagulation Reinitiation After Intracranial Hemorrhage in Patients With Mechanical Valves: A Meta-Analysis

BACKGROUND AND OBJECTIVES: In patients with mechanical heart valves (MHVs), anticoagulation (AC) interruption after intracranial hemorrhage (ICH) poses a clinical dilemma because of competing risks of ischemic complications and hemorrhagic recurrence. To date, the optimal timing for resuming vitamin K antagonists (VKAs) remains unclear. The aim of this meta-analysis was to quantify the risks of ischemic stroke and recurrent ICH associated with VKA resumption in this population and explore the temporal risk dynamics. METHODS: We systematically searched PubMed, Embase, and Cochrane Library from inception to December 2023 for studies reporting ischemic or hemorrhagic outcomes in adults with MHVs who experienced ICH and were considered for VKA resumption. Primary outcomes were ischemic stroke before AC resumption and recurrent ICH after AC resumption. Random-effects meta-analyses were performed. Meta-regressions assessed whether timing of resumption influenced risk. Risk trajectories were estimated using a model-based approach. RESULTS: Nine studies were included, comprising 435 patients with MHVs with confirmed ICH included in the pooled analysis. The mean age ranged from 54.1 to 75 years; 31.3% were female. The pooled incidence of recurrent ICH after AC reinitiation was 11.4% (95% CI 8.2-15.6; I2 = 0%), the incidence of ischemic stroke during AC suspension was 6.1% (95% CI 4.1-8.9; I2 = 0%), valve thrombosis occurred in 3.3% (95% CI 1.9-5.6; I2 = 0%), and mortality occurred in 4.9% (95% CI 2.0-11.5; I2 = 37%). Meta-regression demonstrated a significant inverse association between time to AC resumption and risk of recurrent ICH (regression coefficient -0.039; 95% CI -0.093 to 0.015; p = 0.13), corresponding to an approximate 50% relative reduction in risk at 11 days after ICH. No significant time-dependent association was observed for ischemic stroke (coefficient -0.013; 95% CI -0.065 to 0.039; p = 0.61). DISCUSSION: In patients with MHVs who experienced an ICH, this meta-analysis found that resumption of AC was associated with a recurrent ICH rate of 11.4% and an ischemic stroke rate of 6.1% during AC suspension. Meta-regression suggested a lower risk of recurrent ICH with later AC resumption, with a potential risk reduction at approximately 11 days after ICH. No time-dependent increase in ischemic stroke was observed. Limitations include the retrospective design of most studies and heterogeneous AC timing across cohorts.