Effect of fondaparinux 2.5 mg once daily on mortality: a meta-analysis of phase III randomized trials of venous thromboembolism prevention
Thrombosis Service, McMaster Clinic, Hamilton Health Sciences-General Hospital, Hamilton, ON, Canada
* Corresponding author. Tel: +11 905 521 2100; fax: +11 905 521 1551. E-mail address: eikelbj{at}mcmaster.ca
Aims: Fondaparinux significantly reduces death in patients with acute coronary syndromes. The effect of fondaparinux on mortality when used for prevention of venous thromboembolism is unknown. We performed a meta-analysis to examine the effect of fondaparinux 2.5 mg once daily on mortality in phase III randomized trials of venous thromboembolism prevention.
Methods and results: Eight trials involving 13 085 patients undergoing major orthopaedic or abdominal surgery or medical patients were included. In five trials, fondaparinux was compared with low-molecular-weight heparin (LMWH); in three trials, the comparator was placebo. The primary efficacy outcome was all-cause mortality up to day 30. The incidence of death was 1.6% (105/6538) in patients treated with fondaparinux compared with 2.1% (134/6547) in patients treated with placebo or LMWH [odds ratio (OR) 0.79; 95% confidence interval (CI) 0.60 to 1.01, P = 0.058; P for heterogeneity = 0.58]. Results were consistent irrespective of whether the comparator was placebo (2.0 vs. 2.6%, OR 0.77; 95% CI: 0.46–1.26) or LMWH (1.5 vs. 1.9%, OR 0.78; 95% CI: 0.58–1.06).
Conclusion: The one-fifth reduction in mortality with fondaparinux suggested in randomized trials of venous thromboembolism prevention is not statistically significant, but is externally consistent with the reduction in mortality observed in registry studies and in randomized trials of fondaparinux in patients with acute coronary syndromes.
Key Words: Fondaparinux • Low-molecular-weight heparins • Clinical trial • Mortality • Thromboprophylaxis • Venous thromboembolism