Geno Merli, MD, FACP, FHM; Alex C. Spyropoulos, MD, FACP, FCCP; Joseph A. Caprini, MD, MS, FACS. Annals of Surgery. 09/08/2009
Objective: A review of clinical data from oral anticoagulant studies in orthopedic/general surgery and extrapolation to actual clinical practice.
Summary Background Data: In all surgical patients, there is a risk of postoperative venous thromboembolism (VTE). Parenteral unfractionated heparin, low-molecular-weight heparin, and fondaparinux are available for VTE prophylaxis. Vitamin K antagonists, the only available oral anticoagulants, are widely used in the United States for thromboprophylaxis in joint replacement surgery in spite of being associated with several disadvantages, limiting their effectiveness in the postoperative setting. The oral direct thrombin inhibitor ximelagatran, briefly approved outside the United States for thromboprophylaxis in orthopedic patients, was discontinued due to severe hepatotoxicity concerns. Recently, the oral factor Xa inhibitors rivaroxaban and apixaban have entered late phase development for VTE thromboprophylaxis and treatment and the oral direct thrombin inhibitor dabigatran has received marketing approval from the European Medicines Agency.
Methods: Review of clinical studies of the oral anticoagulants in VTE prevention in orthopedic surgery and comparison with large observational registries.
Results: Results from Phase II/III studies suggest that new oral anticoagulants may provide an efficacious alternative in VTE prevention in orthopedic surgery. Furthermore, these new oral agents have, so far, shown a good overall safety profile, with no evidence of increased hepatotoxicity. However, comparison with large observational registries reveals differences between real-life patient populations, which make extrapolation of clinical trial data to actual clinical practice difficult. Differences in endpoint definitions also prevent indirect comparison of agents. Specific compliance and postmarketing safety issues (especially liver enzyme monitoring requirements) need to be clarified before these agents are widely accepted into routine clinical practice.
Conclusions: Although new oral anticoagulants appear promising, clinical trial results should be viewed with caution until they can be replicated in routine care settings across a broad spectrum of surgical patients.