EFFICACY AND SAFETY OF ENOXAPARIN TO PREVENT DEEP VENOUS THROMBOSIS AFTER HIP-REPLACEMENT SURGERY

Objective: To determine the most effective and safe dose of enoxaparin to prevent deep venous thrombosis in high-risk surgical patients. Des ign: A double-blind, randomized, multicenter clinical trial. Setting: Private, university, and government hospitals in the United States. Pa tients: 572 patients having elective hip replacement surgery, 568 of w hom received study medication and had efficacy data available for eval uation. interventions: Patients were randomly assigned to one of three subcutaneous enoxaparin regimens: 10 mg once daily (161 patients); 40 mg once daily (199 patients); and 30 mg every 12 hours (208 patients) . Treatment was initiated within 24 hours after surgery and continued for as long as 7 days. Treatment with 10 mg enoxaparin once daily was discontinued prematurely after an interim analysis showed an increased deep venous thrombosis incidence in this treatment group. Measurement s: Efficacy was determined by bilateral lower extremity venography, no ninvasive vascular imaging methods, or clinical evidence on day 7 of t reatment ment or earlier if clinically indicated. Results: Deep venous thrombosis occurred in 25% (40 of 161) of the patients who received 1 0 mg of enoxaparin once daily; in 14% (27 of 199) of those receiving 4 0 mg of enoxaparin once daily; and in 11% (22 of 208) in those receivi ng 30 mg of enoxaparin every 12 hours. The incidence of deep venous th rombosis was significantly higher in patients who received 10 mg of en oxaparin once daily compared with those who received 40 mg of enoxapar in once daily (P = 0.02) or those who received 30 mg of enoxaparin eve ry 12 hours (P < 0.001). The difference between the patients who recei ved 40 mg once daily and those who received 30 mg every 12 hours was n ot significant. Only two cases of pulmonary embolism were diagnosed, o ne in patients receiving 40 mg of enoxaparin and one in those receivin g 10 mg once daily. The incidence of hemorrhagic complications differe d significantly between patients who received 10 mg of enoxaparin once daily (5%, 8 of 161 patients) and those who received 30 mg of enoxapa rin every 12 hours (13%, 26 of 208; P < 0.05). Conclusions: After surg ery, enoxaparin, 40 mg once daily or 30 mg every 12 hours, is more eff ective than a regimen of 10 mg once daily to prevent deep venous throm bosis in patients having elective hip replacement surgery. The regimen s of 40 mg once daily and 30 mg every 12 hours provided prophylaxis si milar to the most effective drug treatments previously reported. The i ncidence of hemorrhagic episodes with the regimens of 40 mg once daily and 30 mg twice daily,was higher than that observed with 10 mg once d aily; however, major hemorrhage occurred in only 4% to 5% of patients receiving the higher-dose regimens. The risk-to-benefit ratio supports the use of enoxaparin as a therapeutic agent to prevent deep venous t hrombosis in these patients.