STUDY OBJECTIVES: To assess the relevance of various efficacy end points established for thromboprophylaxis trials, we compared the results of the fondaparinux phase III program in major orthopedic surgery using the original primary efficacy end point with those obtained when the efficacy end points recently suggested by the American College of Chest Physicians (ACCP) Consensus Conference on Antithrombotic Therapy and the European Committee for Proprietary Medicinal Products (CPMP) were used. SETTING AND PATIENTS: Fondaparinux was compared with enoxaparin in four multicenter, randomized, double-blind trials of major orthopedic surgery. The original primary efficacy end point consisted of a composite of deep-vein thrombosis detected by mandatory bilateral venography, documented symptomatic deep-vein thrombosis, or pulmonary embolism up to day 11. The efficacy end point established by the ACCP Consensus Conference on Antithrombotic Therapy comprises any proximal deep-vein thrombosis, symptomatic proven deep-vein thrombosis or pulmonary embolism, or fatal pulmonary embolism, and that established by the European CPMP comprises any proximal deep-vein thrombosis, symptomatic proven pulmonary embolism, or death from any cause. INTERVENTIONS: Patients were randomized to receive either subcutaneous fondaparinux (2.5 mg once daily) starting postoperatively or approved enoxaparin regimens. RESULTS: Using the original end point of the fondaparinux studies, the incidence of venous thromboembolism was 13.7% (371 of 2,703 patients) in the enoxaparin group compared with 6.8% (182 of 2,682 patients) in the fondaparinux group, with a common odds reduction of 55.2% (p = 10(-17); 95% confidence interval, 45.8% to 63.1%) in favor of fondaparinux. The respective incidences of efficacy end points with enoxaparin and fondaparinux were 3.3% and 1.7%, respectively, according to the ACCP definition, and 3.9% and 2.1%, respectively, according to the CPMP definition. The common odds reduction in favor of fondaparinux was 49.6% (p < 0.001) and 48.0% (p < 0.001), respectively. CONCLUSIONS:Fondaparinux was consistently more effective than enoxaparin in preventing venous thromboembolism in patients undergoing major orthopedic surgery, irrespective of the established composite outcomes used.
RCT Entities:
STUDY OBJECTIVES: To assess the relevance of various efficacy end points established for thromboprophylaxis trials, we compared the results of the fondaparinux phase III program in major orthopedic surgery using the original primary efficacy end point with those obtained when the efficacy end points recently suggested by the American College of Chest Physicians (ACCP) Consensus Conference on Antithrombotic Therapy and the European Committee for Proprietary Medicinal Products (CPMP) were used. SETTING AND PATIENTS: Fondaparinux was compared with enoxaparin in four multicenter, randomized, double-blind trials of major orthopedic surgery. The original primary efficacy end point consisted of a composite of deep-vein thrombosis detected by mandatory bilateral venography, documented symptomatic deep-vein thrombosis, or pulmonary embolism up to day 11. The efficacy end point established by the ACCP Consensus Conference on Antithrombotic Therapy comprises any proximal deep-vein thrombosis, symptomatic proven deep-vein thrombosis or pulmonary embolism, or fatal pulmonary embolism, and that established by the European CPMP comprises any proximal deep-vein thrombosis, symptomatic proven pulmonary embolism, or death from any cause. INTERVENTIONS:Patients were randomized to receive either subcutaneous fondaparinux (2.5 mg once daily) starting postoperatively or approved enoxaparin regimens. RESULTS: Using the original end point of the fondaparinux studies, the incidence of venous thromboembolism was 13.7% (371 of 2,703 patients) in the enoxaparin group compared with 6.8% (182 of 2,682 patients) in the fondaparinux group, with a common odds reduction of 55.2% (p = 10(-17); 95% confidence interval, 45.8% to 63.1%) in favor of fondaparinux. The respective incidences of efficacy end points with enoxaparin and fondaparinux were 3.3% and 1.7%, respectively, according to the ACCP definition, and 3.9% and 2.1%, respectively, according to the CPMP definition. The common odds reduction in favor of fondaparinux was 49.6% (p < 0.001) and 48.0% (p < 0.001), respectively. CONCLUSIONS:Fondaparinux was consistently more effective than enoxaparin in preventing venous thromboembolism in patients undergoing major orthopedic surgery, irrespective of the established composite outcomes used.