Major bleeding, mortality, and efficacy of fondaparinux in venous thromboembolism prevention trials.
BACKGROUND
Bleeding is a strong predictor of death in patients hospitalized for arterial thrombosis who are treated with antithrombotic therapy, but the prognostic importance of bleeding in patients receiving antithrombotic prophylaxis for venous thromboembolism is uncertain.


RESULTS
Using Cox proportional hazards modeling, we examined the association between major bleeding and death at 30 days using pooled individual patient data from 8 large randomized controlled trials (n=13 085) comparing fondaparinux with control (low-molecular-weight heparin or placebo) for the prophylaxis of venous thromboembolism in hospitalized surgical or medical patients. Patients who developed major bleeding were older, were more likely to be male, had a lower body weight and lower creatinine clearance, and were more likely to be receiving fondaparinux. At 30 days, the risk of death was 7-fold higher among patients with a major bleeding event (8.6% versus 1.7%; adjusted hazard ratio, 6.96; 95% confidence interval, 4.60 to 10.51). There was a consistent pattern of reduced mortality in patients treated with fondaparinux irrespective of whether patients experienced major bleeding (6.8% versus 11.4%; hazard ratio, 0.58; 95% confidence interval, 0.27 to 1.23) or no major bleeding (1.5% versus 1.9%; hazard ratio, 0.77; 95% confidence interval, 0.59 to 1.02; P for heterogeneity=0.47).


CONCLUSIONS
Major bleeding in hospitalized surgical and medical patients participating in venous thromboembolism prevention trials is a strong predictor of mortality.
Eikelboom
John W
JW
Thromboembolism Unit, Hamilton General Hospital, Hamilton, Ontario, L8L 2X2, Canada. eikelbj@mcmaster.ca
Quinlan
Daniel J
DJ
O'Donnell
Martin
M
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000008:administration & dosage / Q000009:adverse effects*; D017326:Clinical Trials, Phase III as Topic; D005260:Female; D000077425:Fondaparinux; D006470:Hemorrhage / Q000139:chemically induced / Q000401:mortality*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011134:Polysaccharides / Q000008:administration & dosage / Q000009:adverse effects*; D016016:Proportional Hazards Models; D016032:Randomized Controlled Trials as Topic; D012307:Risk Factors; D012737:Sex Factors; D013997:Time Factors; D054556:Venous Thromboembolism / Q000401:mortality* / Q000517:prevention & control*
D000925:Anticoagulants; D011134:Polysaccharides; D000077425:Fondaparinux