USE OF ENOXAPARIN, A LOW-MOLECULAR-WEIGHT HEPARIN, AND UNFRACTIONATEDHEPARIN 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 physician s, patients, and staff were not blinded with regard to the regimen tha t had been used) was conducted, between December 1988 and September 19 90, 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 repla cement. Six hundred and ten patients were randomized, and 607 patients received one of the study medications. The evaluations of efficacy in cluded contrast-media venography, non-invasive vascular examination, a nd clinical examination. Data on efficacy were available for 604 patie nts, who had been assigned to one of three treatment groups: thirty mi lligrams of enoxaparin every twelve hours (194 patients), forty millig rams of enoxaparin once daily (203 patients), or 5000 units of unfract ionated heparin every eight hours (207 patients). All drugs were admin istered subcutaneously. Dosages were not adjusted on the basis of the results of coagulation tests or the body weight of the patient. Treatm ent was initiated within twenty-four hours after the operation and con tinued 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 tw elve hours, thirty (15 per cent) of the 203 patients who received fort y milligrams of enoxaparin once daily, and twenty-four (12 per cent) o f the 207 patients who received unfractionated heparin. The rate of de ep venous thrombosis was significantly lower in the group that receive d 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 c linically symptomatic pulmonary embolism was observed during the treat ment or follow-up phase of this study in the group that received thirt y milligrams of enoxaparin every twelve hours. Analysis of evaluable p atients revealed a marked reduction in the rate of deep venous thrombo sis in the group that received thirty milligrams of enoxaparin every t welve hours (eight [6 per cent] of 136 patients) compared with the gro up 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-pati ent analysis did reveal a significant difference in the rate of deep v enous thrombosis between the group that received thirty milligrams of enoxaparin every twelve hours and the group that received forty millig rams of enoxaparin once daily (twenty-eight [21 per cent] of 136 patie nts) (p = 0.0003). There were eight major bleeding episodes in the gro up that received thirty milligrams of enoxaparin every twelve hours, t hree in the group that received forty milligrams of enoxaparin once da ily, and thirteen in the group that received unfractionated heparin. N o significant difference in the rate of hemorrhagic complications was observed between the group that received thirty milligrams of enoxapar in every twelve hours and the group that received unfractionated hepar in.