Major bleeding predicts mortality in VTE prevention trials

We know that major bleeding is a marker for increased mortality in trials of acute coronary syndrome.  But the impact of major bleeding in VTE prevention has not been entirely elucidated. Eikelboom and colleagues from McMaster University have examined the association between major bleeding and death at 30 days. They used pooled individual patient data from 8 large randomized controlled trials in more than 13,000 patients comparing fondaparinux with either low molecular weight heparin or placebo for VTE prophylaxis. The risk of death was 7-fold higher among patients with a major bleeding event. On the other hand, there was reduced mortality in patients treated with fondaparinux, regardless of major bleeding. The death rate was 42% lower in those fondaparinux treated patients with major bleeding and was 23% lower in those fondaparinux patients without major bleeding. Therein lies a paradox. 

See:

Eikelboom JW, Quinlan DJ, O’Donnell M. Major bleeding, mortality, and efficacy of fondaparinux in venous thromboembolism prevention trials. Circulation 2009; 120: 2006-2011.