Restarting Anticoagulant Therapy After Intracranial Hemorrhage

Atrial fibrillation increases the risk of stroke 3to 5-fold and is implicated in about 15% of all strokes every year. Anticoagulation therapy has been proven to be efficacious in reducing incident stroke and systemic embolism in patients with atrial fibrillation and mechanical heart valves. However, the benefits of anticoagulation must be carefully weighed against the increased risk of intracranial hemorrhage (ICH) faced by patients receiving anticoagulation therapy. Hence, resumption of anticoagulation after ICH poses a clinical conundrum. The absence of evidence-based guidelines to address this issue has led to wide variations in restarting anticoagulation after ICH. Premature reinstatement of anticoagulation could potentially increase recurrent ICH risk, whereas an unnecessary delay in restarting anticoagulation could considerably increase a patient’s thromboembolic risk. Furthermore, there is also no consensus on the timing of reinstitution of these medications. Individual studies in the literature have attempted to address this clinical challenge and have been unable to provide clear guidance on this issue because of small sample sizes and conflicting results. We performed a meta-analysis of available studies to evaluate the safety and efficacy of reinitiation of anticoagulant therapy after ICH. Background and Purpose—The safety and efficacy of restarting anticoagulation therapy after intracranial hemorrhage (ICH) remain unclear. We performed a systematic review and meta-analysis to summarize the associations of anticoagulation resumption with the subsequent risk of ICH recurrence and thromboembolism. Methods—We searched published medical literature to identify cohort studies involving adults with anticoagulationassociated ICH. Our predictor variable was resumption of anticoagulation. Outcome measures were thromboembolic events (stroke and myocardial infarction) and recurrence of ICH. After assessing study heterogeneity and publication bias, we performed a meta-analysis using random-effects models to assess the strength of association between anticoagulation resumption and our outcomes. Results—Eight studies were eligible for inclusion in the meta-analysis, with 5306 ICH patients. Almost all studies evaluated anticoagulation with vitamin K antagonists. Reinitiation of anticoagulation was associated with a significantly lower risk of thromboembolic complications (pooled relative risk, 0.34; 95% confidence interval, 0.25–0.45; Q=5.12, P for heterogeneity=0.28). There was no evidence of increased risk of recurrent ICH after reinstatement of anticoagulation therapy, although there was significant heterogeneity among included studies (pooled relative risk, 1.01; 95% confidence interval, 0.58–1.77; Q=24.68, P for heterogeneity <0.001). No significant publication bias was detected in our analyses. Conclusions—In observational studies, reinstitution of anticoagulation after ICH was associated with a lower risk of thromboembolic complications and a similar risk of ICH recurrence. Randomized clinical trials are needed to determine the true risk–benefit profile of anticoagulation resumption after ICH. (Stroke. 2017;48:1594-1600. DOI: 10.1161/ STROKEAHA.116.016327.)