Background: Extended-duration low-molecular-weight heparin has been shown to prevent venous thromboembolism (VTE) in high-risk surgical patients.
Objective: To evaluate the efficacy and safety of extended-duration enoxaparin thromboprophylaxis in acutely ill medical patients.
Design: Randomized, parallel, placebo-controlled trial. Randomization was computer-generated. Allocation was centralized. Patients, caregivers, and outcome assessors were blinded to group assignment. (ClinicalTrials.gov registration number: NCT00077753)
Setting: 370 sites in 20 countries across North and South America, Europe, and Asia.
Patients: Acutely ill medical patients 40 years or older with recently reduced mobility (bed rest or sedentary without [level 1] or with [level 2] bathroom privileges). Eligibility criteria for patients with level 2 immobility were amended to include only those who had additional VTE risk factors (age >75 years, history of VTE, or active or previous cancer) after interim analyses suggested lower-than-expected VTE rates.
Intervention: Enoxaparin, 40 mg/d subcutaneously (2975 patients), or placebo (2988 patients), for 28Â Â±Â 4 days after receiving open-label enoxaparin for an initial 10Â Â±Â 4 days.
Measurements: Incidence of VTE up to day 28 and of major bleeding events up to 48 hours after the last study treatment dose.
Results: Extended-duration enoxaparin reduced VTE incidence compared with placebo (2.5% vs. 4%; absolute risk difference favoring enoxaparin, âˆ’1.53% [95.8% CI, âˆ’2.54% to âˆ’0.52%]). Enoxaparin increased major bleeding events (0.8% vs. 0.3%; absolute risk difference favoring placebo, 0.51% [95% CI, 0.12% to 0.89%]). The benefits of extended-duration enoxaparin seemed to be restricted to women, patients older than 75 years, and those with level 1 immobility.
Limitation: Estimates of efficacy and safety for the overall trial population are difficult to interpret because of the change in eligibility criteria during the trial.
Conclusion: Use of extended-duration enoxaparin reduces VTE more than it increases major bleeding events in acutely ill medical patients with level 1 immobility, those older than 75 years, and women.
Primary Funding Source: Sanofi-aventis.