Prolonged enoxaparin therapy to prevent venous thromboembolism after primary hip or knee replacement

Background: Patients undergoing hip or knee joint replacement are at risk f or venous thromboembolic complications for up to twelve weeks postoperative ly. We evaluated the efficacy and safety of a prolonged post-hospital regim en of enoxaparin, a low-molecular-weight heparin, in this patient populatio n. Methods: Following elective total hip or knee replacement, 968 patients rec eived subcutaneous enoxaparin (30 mg twice daily) for seven to ten days, an d 873 were then randomized to receive three weeks of double-blind outpatien t treatment with either enoxaparin (40 mg once daily) or a placebo. The pri mary efficacy end point was the prevalence of objectively confirmed venous thromboembolism or symptomatic pulmonary embolism during the double-blind p hase of treatment. Results: Of the 873 randomized patients, 435 underwent elective total hip r eplacement and 438 underwent elective total knee replacement. Enoxaparin wa s superior to the placebo in reducing the prevalence of venous thromboembol ism in patients treated with hip replacement: 8.0% (eighteen) of the 224 pa tients treated with enoxaparin had venous thromboembolism compared with 23. 2% (forty-nine) of the 211 patients treated with the placebo (p < 0.001; od ds ratio, 3.62; 95% confidence interval, 2.00 to 6.55; relative risk reduct ion, 65.5%). Enoxaparin had no significant:benefit in the patients treated with knee replacement: thirty-eight (17.5%) of the 217 patients treated wit h enoxaparin had venous thromboembolism compared with forty-six (20.8%) of the 221 patients treated with the placebo (p = 0.380; odds ratio, 1.24; 95% confidence interval, 0.76 to 2.02; relative risk reduction, 15.9%). Sympto matic pulmonary embolism developed in three patients, one with a hip replac ement and two with a knee replacement; all had received the placebo. There was no significant difference in the prevalence of hemorrhagic episodes or other types of toxicity between the enoxaparin and placebo-treated groups. Conclusions: Prolonging enoxaparin thromboprophylaxis following hip replace ment for a total of four weeks provided therapeutic benefit, by reducing th e prevalence of venous thromboembolism, without compromising safety. A simi lar benefit was not observed in patients treated with knee replacement.