Use of Enoxaparin Versus Unfractionated Heparin in the Prevention of Venous Thromboembolic Events in Acutely Ill Medical Patients: A Meta-Analysis of Individual Patient Data.

Background The ACCP guidelines recommend prophylaxis with low-molecular-weight-heparin (LMWH) or unfractionated heparin (UFH) to prevent venous thromboembolism (VTE) in acutely ill medical patients. However, there is a paucity of data on the relative benefits of using LMWH versus UFH. A meta-analysis was performed using individual patient data to assess the efficacy of the LMWH enoxaparin versus UFH for VTE prophylaxis in hospitalized medical patients.

Methods A systematic literature review was conducted to identify randomized clinical trials comparing enoxaparin 4000 IU S.C. once-daily versus UFH administered S.C. twice (2 × 5000 IU) or three-times daily (3 × 5000 IU) for VTE prophylaxis. Data from electronic database searches were supplemented by information from trial registries, abstract books, meeting proceedings and the trial sponsors. All investigators or sponsors were contacted to provide individual patient data. Recorded outcomes were VTE, major bleeding, and deaths at day 14 as adjudicated by the adjudication committee of each trial. All trial analyses were performed on an intention-to-treat basis. The pooled analysis was based on the logarithm of the relative risk (RR) weighted by the inverse of the variance.

Results Individual patient data were obtained from 3600 patients enrolled in 4 randomized clinical trials, 3 in stroke patients and 2 in patients with various acute illnesses. The data from 1 additional trial is currently unavailable (100 patients). The median age of evaluated patients was 71 years; 51% are male; 32% presented with a creatinine clearance <50 mL/min. Meta-analysis of the overall incidence of VTE (including asymptomatic DVT, symptomatic VTE and PE-related death) showed a 38% significant reduction in favor of enoxaparin (RR=0.62 [95% CI 0.50–0.77], p<0.001, heterogeneity test p_Het=NS). A non-significant 13% increase in major bleeding was also observed with enoxaparin (RR=1.13 [95% CI 0.53–2.44], p=0.75, p_Het=NS). Finally, there was a non-significant 16% reduction in death with enoxaparin (RR=0.84 [95% CI 0.63–1.10], p=0.20, p_Het=NS).

Conclusion The results of this meta-analysis support superior efficacy of enoxaparin, with a non-significant increase in major bleeding, compared with UFH for VTE prophylaxis in acutely ill medical patients.