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


METHODS
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.


METHODS
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.


METHODS
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.


METHODS
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.


CONCLUSIONS
Estimates of efficacy and safety for the overall trial population are difficult to interpret because of the change in eligibility criteria during the trial.


CONCLUSIONS
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.


BACKGROUND
Sanofi-aventis.
Hull
Russell D
RD
ThrombosisResearch Unit, University of Calgary, Foothills Hospital, Calgary, Alberta, Canada. rdhull@ucalgary.ca
Schellong
Sebastian M
SM
Tapson
Victor F
VF
Monreal
Manuel
M
Samama
Meyer-Michel
MM
Nicol
Philippe
P
Vicaut
Eric
E
Turpie
Alexander G G
AG
Yusen
Roger D
RD
D000208:Acute Disease; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000008:administration & dosage* / Q000009:adverse effects; D003692:Delayed-Action Preparations; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D017984:Enoxaparin / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D006470:Hemorrhage / Q000139:chemically induced; D006760:Hospitalization; D006801:Humans; D007103:Immobilization / Q000009:adverse effects*; D015994:Incidence; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D016896:Treatment Outcome; D054556:Venous Thromboembolism / Q000453:epidemiology / Q000517:prevention & control*
D000925:Anticoagulants; D003692:Delayed-Action Preparations; D017984:Enoxaparin