Comparative effectiveness of low-molecular-weight heparins versus other anticoagulants in major orthopedic surgery: a systematic review and meta-analysis.

To evaluate the comparative efficacy and safety of low-molecular-weight heparins (LMWHs) versus other anticoagulants as venous thromboembolism prophylaxis in major orthopedic surgery. Systematic review with meta-analysis of 37 randomized controlled trials. Patients undergoing total hip replacement, total knee replacement, or hip fracture surgery who received prophylaxis with a LMWH or another anticoagulant. We conducted a systematic literature search of the MEDLINE, Cochrane Central Register of Controlled Trials, and Scopus databases (1980-July 2011) to identify randomized controlled trials. Trials were included if they directly compared LMWH prophylaxis with another anticoagulant class and reported outcomes of interest. Compared with patients who received unfractionated heparin (UFH), patients who received LMWHs had fewer pulmonary embolism, total deep vein thrombosis (DVT), major bleeding, and heparin-induced thrombocytopenia events. Compared with patients who received vitamin K antagonists (VKAs), patients who received LMWHs had fewer total DVT and distal DVT events but reported increased major bleeding, minor bleeding, and surgical site bleeding events. Major efficacy end points such as symptomatic venous thromboembolism, pulmonary embolism, and nonfatal pulmonary embolism showed similar benefits of therapy with LMWHs and VKAs. Compared with patients receiving factor Xa inhibitors, patients who received LMWHs had more major venous thromboembolism, pulmonary embolism, total DVT, asymptomatic DVT, proximal DVT, and distal DVT events but fewer major bleeding events. Compared with patients receiving direct thrombin inhibitors (DTIs), patients who received LMWHs had more major venous thromboembolism, total DVT, and proximal DVT events without significantly negatively affecting bleeding. However, patients who received LMWHs had fewer distal DVT events versus those who received DTIs. Subgroup analyses indicated differences based on the surgical procedure and individual drug within certain pharmacologic classes. According to moderate-to-high strength of evidence, LMWH prophylaxis provides additional benefits with less harm compared with UFH. With predominantly moderate strength of evidence, the balance of benefits to harms for factor Xa inhibitors or DTIs compared with LMWHs seems favorable. With predominantly low-to-moderate strength of evidence, the known benefits in total DVT and distal DVT with LMWHs versus VKAs may not be sufficient to counteract the increased risk of bleeding.