Direct factor Xa inhibitors versus low molecular weight heparins or vitamin K antagonists for prevention of venous thromboembolism in elective primary hip or knee replacement or hip fracture repair

BACKGROUND: People undergoing major orthopaedic surgery are at increased risk of postoperative thromboembolic events. Low molecular weight heparins (LMWHs) are recommended for thromboprophylaxis in this population. New oral anticoagulants, including direct factor Xa inhibitors, are recommended as alternatives. They may have more advantages than disadvantages compared to LMWHs and vitamin K antagonists (VKAs, another type of anticoagulant). OBJECTIVES: To assess the benefits and harms of prophylactic anticoagulation with direct factor Xa inhibitors compared with low molecular weight heparins and vitamin K antagonists in people undergoing major orthopaedic surgery for elective total hip or knee replacement or hip fracture surgery. SEARCH METHODS: We searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase, two other databases, and two trial registers to 11 November 2023. We conducted reference checks to identify additional studies. SELECTION CRITERIA: We included randomised controlled trials (RCTs) comparing the effects of direct factor Xa inhibitors to LMWHs or VKAs in people undergoing major orthopaedic surgery. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were all-cause mortality, major venous thromboembolism (VTE), symptomatic VTE, major bleeding, and serious hepatic and non-hepatic adverse events. We evaluated the risk of bias in the included studies using Cochrane's risk of bias 1 tool. We calculated estimates of treatment effects using risk ratios (RR) with 95% confidence intervals (CIs), and used GRADE criteria to assess the certainty of the evidence. MAIN RESULTS: = 18%; 15 studies, 26,246 participants; low-certainty evidence). The absolute benefit of substituting factor Xa inhibitors for LMWH may be between three and 14 fewer serious non-hepatic adverse events per 1000 patients. Only one study compared a direct factor Xa inhibitor with a VKA. It reported outcome data with imprecise results due to the small number of events. It showed no difference in the effects of the study drugs. AUTHORS' CONCLUSIONS: Oral direct factor Xa inhibitors may have little to no effect on all-cause mortality, but the evidence is very uncertain. Oral direct factor Xa inhibitors may slightly reduce symptomatic VTE events when compared with LMWH. They may make little or no difference to major VTE events, but the evidence is very uncertain. In the evaluation of major bleeding, the evidence suggests rivaroxaban results in a slight increase in major bleeding events compared to LMWHs. The remaining oral direct factor Xa inhibitors may have little to no effect on major bleeding, but the evidence is very uncertain. Oral direct factor Xa inhibitors may reduce serious non-hepatic adverse events slightly compared to LMWHs. They may have little to no effect on serious hepatic adverse events, but the evidence is very uncertain. Due to the high rates of missing participants and selective outcome reporting, the effect estimates may be biased.