Thromboprophylaxis with apixaban and the risk of pulmonary embolism in patients undergoing knee replacement surgery

Background: Apixaban, a novel oral anticoagulant, is also used for deep vein thrombosis (DVT) prophylaxis. In this study, we sought to critically evaluate the differences in the rates of symptomatic DVT and bleeding, and analyze the rates of pulmonary embolism (PE) in subgroups of patients from ADVANCE I and II trials given their similar indication and design. Methods: Studies were identified through electronic literature searches of MEDLINE, clinicaltrial. gov, SCOPUS, and EMBASE up to January 2014. Phase III RCTs involving use of apixaban and enoxaparin for thromboprophylaxis in patients undergoing total knee or hip replacement were included. Study-specific odds ratios were calculated and between-study heterogeneity was assessed using the I-2 statistics. Results: In three studies involving 11,659 patients, the risk of symptomatic DVT (pooled OR 0.38, 95% CI 0.16-0.90, I-2 = 0%, p = 0.03) and bleeding (pooled OR 0.87, 95% CI 0.77-0.99, I-2 = 0%, p = 0.03) was less in apixaban group compared to the enoxaparin group. However, it was interesting to note that on subgroup analysis, the risk of PE was higher with apixaban when used for thromboprophylaxis in knee replacement surgery (pooled OR 2.58, 95% CI 1.10-6.04, I-2 = 0%, p = 0.03). Conclusion: Apixaban was found to be associated with lower risk of symptomatic DVT and bleeding compared to enoxaparin when used for thromboprophylaxis in patients undergoing knee and hip replacement surgeries. However, it was associated with higher risk of PE in patients undergoing knee replacement.