Extended-duration venous thromboembolism prophylaxis in acutely ill medical patients with recently reduced mobility: a randomized trial

Ann Intern Med. 2010 Jul 6;153(1):8-18. doi: 10.7326/0003-4819-153-1-201007060-00004.

Abstract

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 28 +/- 4 days after receiving open-label enoxaparin for an initial 10 +/- 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, -1.53% [95.8% CI, -2.54% to -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.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Adult
  • Aged
  • Aged, 80 and over
  • Anticoagulants / administration & dosage*
  • Anticoagulants / adverse effects
  • Delayed-Action Preparations
  • Double-Blind Method
  • Drug Administration Schedule
  • Enoxaparin / administration & dosage*
  • Enoxaparin / adverse effects
  • Female
  • Hemorrhage / chemically induced
  • Hospitalization*
  • Humans
  • Immobilization / adverse effects*
  • Incidence
  • Male
  • Middle Aged
  • Risk Factors
  • Treatment Outcome
  • Venous Thromboembolism / epidemiology
  • Venous Thromboembolism / prevention & control*

Substances

  • Anticoagulants
  • Delayed-Action Preparations
  • Enoxaparin

Associated data

  • ClinicalTrials.gov/NCT00077753