Efficacy and safety of bemiparin compared with enoxaparin in the prevention of venous thromboembolism after total knee arthroplasty: a randomized, double-blind clinical trial

Abstract

In this randomized, multicenter, controlled, double-blind, sequential trial, 381 patients undergoing primary total knee replacement were randomly assigned to receive subcutaneous injections of either 3500 IU anti-factor Xa of bemiparin sodium, first dose 6 h after surgery, or 40 mg of enoxaparin, first dose 12 h before surgery, followed by daily doses for 10 +/- 2 days, for the prophylaxis of venous thromboembolism. The primary efficacy endpoint was venous thromboembolism up to postoperative day 10 +/- 2, defined as deep vein thrombosis detected by mandatory bilateral venography, documented symptomatic deep vein thrombosis and/or documented symptomatic pulmonary embolism. The primary safety endpoint was major bleeding. Eighty-seven percent of all randomized patients (333 of 381 patients) were evaluable for efficacy. The incidence of venous thromboembolism was 32.1% (53 of 165 patients) in the bemiparin group and 36.9% (62 of 168 patients) in the enoxaparin group. The absolute risk difference was 4.8% in favor of bemiparin [95% confidence interval (CI), -15.1% to 5.6%; non-inferiority P-value: 0.02; superiority P-value: 0.36]. The incidence of proximal deep vein thrombosis was 1.8% (three of 165 patients) in the bemiparin group and 4.2% (seven of 168 patients) in the enoxaparin group. Major bleeding occurred in six patients (three in each group). There were no deaths during the study. This trial shows that bemiparin started postoperatively is as effective and safe as enoxaparin started preoperatively in the prevention of venous thromboembolism in patients undergoing total knee replacement.