Prevention of venous thromboembolism in patients with immobilization of the lower extremities:: a meta-analysis of randomized controlled trials

Background: It is controversial whether the prevention of venous thromboembolism (VTE) in patients with lower-leg immobilization is necessary. Objectives: To assess the benefits and complications of pharmacological thromboprophylaxis, we performed a meta-analysis of all available randomized controlled trials on this subject. Methods: We searched the MEDLINE and EMBASE electronic databases. We included English- and non-English language studies, we hand-searched journals, and we contacted manufacturers. We analyzed data from six randomized trials that investigated pharmacological prophylaxis for the prevention of VTE in 1456 patients with lower-leg immobilization in plaster cast or orthosis. Two reviewers independently assessed the trials for inclusion, extracted data, and assessed trial quality. Differences were resolved by consensus or arbitrage. Results: The pooled estimate from all trials revealed a highly significant and clinically relevant reduction in asymptomatic events with low-molecular-weight heparin (LMWH) prophylaxis, compared to placebo or untreated control [risk ratio (RR) 0.58; 95% confidence interval (CI) 0.39-0.86; P = 0.006). The mean rate of VTE decreased from 17.1% to 9.6% with the use of LMWH. Subgroup analysis of methodologically superior trials (RR 0.68; CI 0.50-0.92; P = 0.01), proximal deep vein thrombosis (RR 0.28; CI 0.11-0.72; P = 0.008), tendon ruptures (RR 0.60; CI 0.38-0.97; P = 0.04), and fractures (RR 0.62; CI 0.45-0.86; P = 0.004) confirmed the robustness of the overall result. Frequency of bleeding did not differ between LMWH prophylaxis and control groups (RR 1.22; CI 0.61-2.46; P = 0.57). Conclusions: Our findings indicate that thromboprophylaxis with LMWH for immobilization of the lower extremities reduces the risk of VTE. This benefit is achieved with no excess bleeding.