Extended-duration prophylaxis against venous thromboembolism after total hip or knee replacement: a meta-analysis of the randomised trials

Background The optimum duration of prophylaxis against venous-thromboembolism after total hip or knee replacement is uncertain. Our primary objective was to establish the efficacy of extended-duration prophylaxis on symptomatic venous thromboembolic events. Methods We identified randomised trials comparing extended-duration prophylaxis using heparin or warfarin with placebo or untreated control in patients undergoing elective total hip or knee replacement by searching electronic databases (MEDLINE, EMBASE), references from retrieved articles, and abstracts from conference proceedings, and by contact with pharmaceutical companies and investigators. Two reviewers independently extracted data on study design, symptomatic and symptomless venographic venous thromboembolism, death, and bleeding outcomes. Results from individual trials were combined with the Mantel-Haenszel method. Findings Nine studies met our inclusion criteria (3999 patients), eight with low molecular weight heparin, and one with unfractionated heparin. Extended-duration prophylaxis for 30–42 days significantly reduced the frequency of symptomatic venous thromboembolism (1·3% vs 3·3%, OR 0·38; 95% CI 0·24–0·61, numbers needed to treat [NNT]=50), with no statistical evidence of heterogeneity (χ2 test, p=0·69). There was a greater risk reduction in patients undergoing hip replacement (1·4% vs 4·3%, 0·33; 0·19–0·56, 34) compared with knee replacement (1·0% vs 1·4%, 0·74; 0·26–2·15, 250). A significant reduction in symptomless venographic deep vein thrombosis was also observed (9·6% vs 19·6%, 0·48; 0·36–0·63, 10). There was no increase in major bleeding but extended-duration prophylaxis was associated with excess minor bleeding (3·7% vs 2·5%, 1·56; 1·08–2·26, numbers needed to harm [NNH]=83). Interpretation Among patients undergoing total hip or knee replacement, extended-duration prophylaxis significantly reduces the frequency of symptomatic venous thromboembolism. The reduction in risk is equivalent to about 20 symptomatic events per 1000 patients treated.