Vitamin K Antagonists and Risk of Subdural Hematoma Meta-Analysis of Randomized Clinical Trials

Background and Purpose-Subdural hematomas are an important bleeding complication of anticoagulation. We quantify the risk of subdural hematoma associated with anticoagulation with vitamin K antagonists (VKAs) compared with other oral antithrombotic therapies. Methods-Randomized trials were identified from the Cochrane Central Register of Controlled Trials and were included if published since 1980 and compared oral VKAs with antiplatelet therapy or with direct-acting oral anticoagulants. Two reviewers independently extracted data with differences resolved by joint review. Results-Nineteen randomized trials were included that involved 92 156 patients and 275 subdural hematomas. By meta-analysis, VKAs were associated with a significantly increased risk of subdural hematoma (odds ratios, 3.0; 95% confidence interval, 1.5-6.1) compared with antiplatelet therapy (9 trials, 11 603 participants). The risk of subdural hematoma was also significantly higher with VKAs versus factor Xa inhibitors (meta-analysis odds ratios, 2.9; 95% confidence interval, 2.1-4.1; 5 trials, 49 687 patients) and direct thrombin inhibitors (meta-analysis odds ratios, 1.8; 95% confidence interval, 1.2-2.7; 5 trials, 30 866 patients) versus VKAs. The absolute rate of subdural hematoma among 24 485 patients with atrial fibrillation treated with VKAs pooled from 6 trials testing direct-acting oral anticoagulants was 2.9 (95% confidence interval, 2.5-3.5) per 1000 patient-years. Conclusions-VKA use significantly increases the risk of subdural hematoma by approximate to 3-fold relative to antiplatelet therapy. Direct-acting oral anticoagulants are associated with a significantly reduced risk of subdural hematomas versus VKAs. Based on indirect comparisons to VKAs, the risks of subdural hematoma are similar with antiplatelet monotherapies and factor Xa inhibitors.