Safety and efficacy of new anticoagulants for the prevention of venous thromboembolism after hip and knee arthroplasty

Context: After hip and knee arthroplasty, venous thromboembolism (VTE) is common and often severe. Dabigatran, apixaban, and rivaroxaban are new anticoagulants that show promise for VTE prevention in this population, and have been proposed to be both safer and more effective than traditional anticoagulants. Current guidelines prefer a low-molecular-weight heparin, such as enoxaparin.

Purpose: To perform a current review of the existing literature and determine which anticoagulant has the best safety and efficacy in hip and knee arthroplasty. Data sources: We searched Pubmed, Medline (through Pubmed), Embase, and Clinicaltrials.gov to find randomized controlled trials of these anticoagulants.

Methods: From 1070 potentially relevant trials, 14 met the inclusion criteria and were included in the final meta-analysis. Information on trial design and duration, drug regimen, dose, frequency, route and clinical outcomes, were extracted systematically. Outcomes were: major bleeding, the composite of major and/or clinically relevant bleeding, and the composite of VTE and/or death.

Results: Compared to enoxaparin, the relative risk (RR) of VTE/death varied significantly with the new anticoagulants. RR of VTE/death was lowest (0.55, 95% CI, 0.46-0.66 p=<0.001) for rivaroxaban (10 mg once daily) and highest (1.20, 95% CI, 0.99-1.44 p=0.058) for dabigatran (150 mg once daily). Apixaban (2.5 mg twice daily) had the lowest RR of major/clinically relevant bleeding (0.84, 95% CI, 0.70-1.01 p=0.058), while rivaroxaban had the highest (1.30, 95% CI, 1.03-1.64 p=0.027).

Conclusions: With the possible exception of apixaban, new anticoagulants that lower the risk of VTE, increase the risk of bleeding. Similarly, new anticoagulants that lower the risk of bleeding, raise the risk of VTE.