Resuming anticoagulants after anticoagulation-associated intracranial haemorrhage: systematic review and meta-analysis

OBJECTIVE: To determine the adverse outcomes following resumption of anticoagulation in patients with anticoagulation-associated intracranial haemorrhage (ICH). DESIGN: We performed a systematic review and meta-analysis in this clinical population. The Preferred Reporting Items for Systemic Reviews and Meta-Analyses statement was followed, and two authors independently assessed eligibility of all retrieved studies and extracted data. DATA SOURCES: Medline, Embase and the Cochrane Central Register of Controlled Trials, from inception to February 2017. ELIGIBILITY CRITERIA AND OUTCOMES: Randomised controlled trials or cohort studies that recruited adults who received oral anticoagulants at the time of ICH occurrence and survived after the acute phase or hospitalisation were searched. Primary outcomes, including long-term mortality, recurrent ICH and thromboembolic events. Secondary outcomes were the frequency of resuming anticoagulant therapy and related factors. RESULTS: We included 12 cohort studies (no clinical trials) involving 3431 ICH participants. The pooled frequency of resuming anticoagulant therapy was 38% (95% CI 32% to 44%), but this was higher in participants with prosthetic heart valves, subarachnoid haemorrhage or dyslipidaemia. There was no evidence that resuming anticoagulant therapy was associated with higher long-term mortality (pooled relative risk (RR) 0.60, 95% CI 0.30 to 1.19; p=0.14) or ICH recurrence (pooled RR 1.14, 95% CI 0.72 to 1.80; p=0.57). Resumption of anticoagulation was associated with significantly fewer thromboembolic events (pooled RR 0.31, 95% CI 0.23 to 0.42; p<0.001). In a subgroup of patients with atrial fibrillation, resuming anticoagulant therapy was associated with fewer long-term mortality (pooled RR 0.27, 95% CI 0.20 to 0.37, p<0.001). CONCLUSIONS: Based on these observational studies, resuming anticoagulant therapy after anticoagulation-associated ICH has beneficial effects on long-term complications. Clinical trials are needed to substantiate these findings. PROSPERO REGISTRATION NUMBER: CRD42017063827.