USE OF ENOXAPARIN, A LOW-MOLECULAR-WEIGHT HEPARIN, AND UNFRACTIONATED HEPARIN FOR THE PREVENTION OF DEEP VENOUS THROMBOSIS AFTER ELECTIVE HIP-REPLACEMENT - A CLINICAL-TRIAL COMPARING EFFICACY AND SAFETY

A randomized, parallel-group, open-label clinical trial (the physicians, patients, and staff were not blinded with regard to the regimen that had been used) was conducted, between December 1988 and September 1990, to compare the safety and efficacy of enoxaparin, a low-molecular-weight heparin,,vith the safety and efficacy of unfractionated heparin for the prevention of deep venous thrombosis after elective hip replacement. Six hundred and ten patients were randomized, and 607 patients received one of the study medications. The evaluations of efficacy included contrast-media venography, non-invasive vascular examination, and clinical examination. Data on efficacy were available for 604 patients, who had been assigned to one of three treatment groups: thirty milligrams of enoxaparin every twelve hours (194 patients), forty milligrams of enoxaparin once daily (203 patients), or 5000 units of unfractionated heparin every eight hours (207 patients). All drugs were administered subcutaneously. Dosages were not adjusted on the basis of the results of coagulation tests or the body weight of the patient. Treatment was initiated within twenty-four hours after the operation and continued for a maximum of seven days. The primary safety outcome was the occurrence of bleeding episodes. An intent-to-treat patient analysis revealed that deep venous thrombosis occurred in nine (5 per cent) of the 144 patients who received thirty milligrams of enoxaparin every twelve hours, thirty (15 per cent) of the 203 patients who received forty milligrams of enoxaparin once daily, and twenty-four (12 per cent) of the 207 patients who received unfractionated heparin. The rate of deep venous thrombosis was significantly lower in the group that received thirty milligrams of enoxaparin every twelve hours than in the group that received unfractionated heparin (p = 0.03) and in the group that received forty milligrams of enoxaparin once daily (p = 0.0002). No clinically symptomatic pulmonary embolism was observed during the treatment or follow-up phase of this study in the group that received thirty milligrams of enoxaparin every twelve hours. Analysis of evaluable patients revealed a marked reduction in the rate of deep venous thrombosis in the group that received thirty milligrams of enoxaparin every twelve hours (eight [6 per cent] of 136 patients) compared with the group that received heparin (twenty-one [15 per cent] of 145 patients) (p = 0.10); however, this difference was not significant because of the small number of patients included in this analysis. The evaluable-patient analysis did reveal a significant difference in the rate of deep venous thrombosis between the group that received thirty milligrams of enoxaparin every twelve hours and the group that received forty milligrams of enoxaparin once daily (twenty-eight [21 per cent] of 136 patients) (p = 0.0003). There were eight major bleeding episodes in the group that received thirty milligrams of enoxaparin every twelve hours, three in the group that received forty milligrams of enoxaparin once daily, and thirteen in the group that received unfractionated heparin. No significant difference in the rate of hemorrhagic complications was observed between the group that received thirty milligrams of enoxaparin every twelve hours and the group that received unfractionated heparin.