EFFICACY AND SAFETY OF POSTDISCHARGE ADMINISTRATION OF ENOXAPARIN IN THE PREVENTION OF DEEP VENOUS THROMBOSIS AFTER TOTAL HIP-REPLACEMENT -A PROSPECTIVE RANDOMIZED DOUBLE-BLIND PLACEBO-CONTROLLED TRIAL

Although venous thromboembolism has occasionally been reported after h ospital discharge in patients who have undergone total hip replacement (THR), this risk has not been fully quantified and the usefulness of a prophylactic treatment has not been evaluated. We conducted a single -centre prospective randomised double-blind clinical trial in 2 parall el groups of patients who had undergone THR and were free of deep veno us thrombosis (DVT) at discharge, as assessed by bilateral ascending v enography. During hospitalisation, all patients received a low molecul ar weight heparin, enoxaparin (enoxaparin sodium), as a prophylactic t reatment for venous thromboembolism. Just before hospital discharge (1 5 +/- 1 days from surgery) 179 consecutive patients were randomly assi gned to receive subcutaneous enoxaparin 40mg (n = 90) or placebo (n = 89) once daily for 21 +/- 2 days. The primary efficacy outcome was def ined as the occurrence of DVT and/or documented pulmonary embolism (PE ). DVT was assessed by ascending bilateral venography performed 21 ri: 2 days after randomisation or earlier if necessarj. Secondary efficacy outcomes were the occurrence of proximal and distal DVT. Safety outco mes were defined as the occurrence of major and minor haemorrhage, oth er adverse events and changes in laboratory parameters. All patients u nderwent a 3-month follow-up. There were no deaths or cases of clinica l PE during the study and the follow-up periods. In 173 patients with evaluable venograms, analysis of efficacy on an intention-to-treat bas is showed that the incidence of DVT at day 21 was significantly lower in the enoxaparin group (6 of 85; 7.1%) than in the placebo group (17 of 88; 19.3%; p = 0.018), a risk reduction of 63%. Distal DVT was less frequent in the enoxaparin group than in the placebo group (1.2 vs 11 .4%; p = 0.006) but there was no significant difference between groups in the incidence of proximal DVT. A 'per-protocol' analysis of effica cy in 155 patients confirmed the results for total and distal DVT, but also showed a trend in efficacy in favour of enoxaparin with regard t o the incidence of proximal DVT (p = 0.064). Enoxaparin was safe in co mparison with placebo: only 2 minor bleedings occurred in the enoxapar in group and there was no difference in the incidence of other adverse events between the 2 groups. In patients undergoing THR, the risk of late-occurring DVT remained high during the 21 days after hospital dis charge in the placebo group. Prophylactic treatment with enoxaparin re duced the risk and was well tolerated in this context.