Low-molecular-weight heparin and mortality in acutely ill medical patients.
BACKGROUND
Although thromboprophylaxis reduces the incidence of venous thromboembolism in acutely ill medical patients, an associated reduction in the rate of death from any cause has not been shown.


METHODS
We conducted a double-blind, placebo-controlled, randomized trial to assess the effect of subcutaneous enoxaparin (40 mg daily) as compared with placebo--both administered for 10±4 days in patients who were wearing elastic stockings with graduated compression--on the rate of death from any cause among hospitalized, acutely ill medical patients at participating sites in China, India, Korea, Malaysia, Mexico, the Philippines, and Tunisia. Inclusion criteria were an age of at least 40 years and hospitalization for acute decompensated heart failure, severe systemic infection with at least one risk factor for venous thromboembolism, or active cancer. The primary efficacy outcome was the rate of death from any cause at 30 days after randomization. The primary safety outcome was the rate of major bleeding during and up to 48 hours after the treatment period.


RESULTS
A total of 8307 patients were randomly assigned to receive enoxaparin plus elastic stockings with graduated compression (4171 patients) or placebo plus elastic stockings with graduated compression (4136 patients) and were included in the intention-to-treat population. The rate of death from any cause at day 30 was 4.9% in the enoxaparin group as compared with 4.8% in the placebo group (risk ratio, 1.0; 95% confidence interval [CI], 0.8 to 1.2; P=0.83). The rate of major bleeding was 0.4% in the enoxaparin group and 0.3% in the placebo group (risk ratio, 1.4; 95% CI, 0.7 to 3.1; P=0.35).


CONCLUSIONS
The use of enoxaparin plus elastic stockings with graduated compression, as compared with elastic stockings with graduated compression alone, was not associated with a reduction in the rate of death from any cause among hospitalized, acutely ill medical patients. (Funded by Sanofi; LIFENOX ClinicalTrials.gov number, NCT00622648.).
Thrombosis Research Institute and University College London, London, United Kingdom. akkakkar@tri-london.ac.uk
Ajay K
AK
Kakkar
Claudio
C
Cimminiello
Samuel Z
SZ
Goldhaber
Rajiv
R
Parakh
Chen
C
Wang
Jean-François
JF
Bergmann
D000208:Acute Disease; D000368:Aged; D000925:Anticoagulants / Q000009:adverse effects / Q000627:therapeutic use*; D002423:Cause of Death; D003131:Combined Modality Therapy; D004311:Double-Blind Method; D017984:Enoxaparin / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006333:Heart Failure / Q000628:therapy; D006470:Hemorrhage / Q000209:etiology; D017052:Hospital Mortality; D006801:Humans; D007239:Infections / Q000628:therapy; D007279:Injections, Subcutaneous; D057194:Intention to Treat Analysis; D008297:Male; D008875:Middle Aged; D053828:Stockings, Compression; D054556:Venous Thromboembolism / Q000517:prevention & control
D000925:Anticoagulants; D017984:Enoxaparin