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

Background The optimum duration of prophylaxis against venous thromboemboli sm after total hip or knee replacement is uncertain, Our primary objective was to establish the efficacy of extended-duration prophylaxis on symptomat ic venous thromboembolic events. Methods We identified randomised trials comparing extended-duration prophyl axis using heparin or warfarin with placebo or untreated control in patient s undergoing elective total hip or knee replacement by searching electronic databases (MEDLINE, EMBASE), references from retrieved articles, and abstr acts from conference proceedings, and by contact with pharmaceutical compan ies and investigators. Two reviewers independently extracted data on study design, symptomatic and symptomless venographic venous thromboembolism, dea th, and bleeding outcomes. Results from individual trials were combined wit h the Mantel-Haenszel method. Findings Nine studies met our inclusion criteria (3999 patients), eight wit h low molecular weight heparin, and one with unfractionated heparin. Extend ed-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 het erogeneity (chi (2) test, p=0.69). There was a greater risk reduction in pa tients undergoing hip replacement (1.4% vs 4.3%, 0.33; 0.19-0.56, 34) compa red with knee replacement (1.0% vs 1.4%, 0.74; 0.26-2.15, 250), A significa nt reduction in symptomless venographic deep vein thrombosis was also obser ved (9.6% vs 19.6%, 0.48; 0.36-0.63, 10). There was no increase in major bl eeding bur extended-duration prophylaxis was associated with excess minor b leeding (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, ext ended-duration prophylaxis significantly reduces the frequency of symptomat ic venous thromboembolism. The reduction in risk is equivalent to about 20 symptomatic events per 1000 patients treated.