New oral anticoagulants increase the risk of gastrointestinal bleeding - A systematic review and meta-analysis

OBJECTIVE: To investigate the risk of gastrointestinal bleeding (GIB) and clinically relevant bleeding in patients taking the new oral anticoagulants (nOACs). DESIGN: Systematic review and meta-analysis. METHOD: We queried MEDLINE, Embase, and the Cochrane database (up to July 2012). We analyzed data from 43 randomized controlled trials (151,578 patients) that compared nOACs (regardless of indication) with standard care. RESULTS: All studies reported on clinically relevant bleeding and 19 explicitly on GIB. The odds ratio (OR),for GIB among patients taking nOACs was 1.45 (95% confidence interval (CI): 1.07-1.97). There was substantial heterogeneity among studies (I2 = 61%). Subgroup analyses showed that the OR for atrial fibrillation was 1.21 (95% CI: 0.91-1.61), for thromboprophylaxis after orthopaedic surgery was 0.78 (95% CI: 0.31-1.96), for treatment of venous thrombosis was 1.59 (95% CI: 1.03-2.44), and for acute coronary syndrome (ACS) was 5.21 (95% CI: 2.58-10.53). Among the drugs studied, the OR for apixaban was 1.23 (95% CI: 0.56-2.73), the OR for dabigatran was 1.58 (95% CI:1.29-1.93), the OR for edoxaban was 0.31 (95% CI: 0.01-7.69), and the OR for rivaroxaban was 1.48 (95% CI: 1.21-1.82). The overall OR for clinically relevant bleeding in patients taking nOACs was 1.16 (95% CI: 1.00-1.34). CONCLUSION: Patients with venous thrombosis or acute coronary syndrome treated with an nOAC have an increased risk of GIB compared to those who receive standard care. The latter indication is not registered in the Netherlands, however. The individual risk profile is critical in the choice of nOAC.