The role of fondaparinux as an adjunct to thrombolytic therapy in acute myocardial infarction: a subgroup analysis of the OASIS-6 trial
1 Department of Cardiology, Academic Medical Center, Room F3-236, P.O. Box 22660, 1100 DD Amsterdam, The Netherlands
2 Division of Cardiology, University of Toronto and Sunnybrook Health Sciences Centre, Toronto, ON, Canada
3 Division of Cardiology, University of Besancon, Besancon, France
4 Population Health Research Institute and Department of Medicine, McMaster University and Hamilton Health Sciences, Hamilton, ON, Canada
5 Uppsala Clinical Research Center, Uppsala University Hospital, Uppsala, Sweden
6 Division of Cardiology, Grochowski Hospital, Warsaw, Poland
7 Cardiovascular Research Division, University of Edinburgh, Edinburgh, UK
Received 15 September 2006; revised 11 December 2007; accepted 13 December 2007.
* Corresponding author: Tel: +31 20 5666952, Fax: +31 20 5669747. Email: r.j.peters{at}amc.uva.nl
Aims: No antithrombotic therapy has been shown to reduce mortality when used with thrombolytics in acute myocardial infarction (AMI). In the OASIS-6 trial, fondaparinux significantly reduced mortality and reinfarction without increasing bleeding in 12 092 patients with acute ST elevation MI.
Methods and results: We report the results of a subgroup analysis in the 5436 patients (45%) receiving thrombolytics. According to local practice, 4415 patients did not have an indication for unfractionated heparin (stratum 1) and 1021 did (stratum 2). Fondaparinux reduced the primary study outcome of death or MI at 30 days [Hazard ratio (HR) 0.79, 95% confidence interval (CI) 0.68–0.92] with consistent reductions in both mortality (HR and CI) and reinfarction (HR and CI). There was a non-significantly lower rate of stroke (HR 0.77, CI 0.48–1.25). The risk of severe bleeding was significantly reduced (HR 0.62, CI 0.40–0.94), and thus the balance of benefit and risk (death, MI and severe haemorrhage) was clearly reduced by fondaparinux (HR 0.77, 95% CI 0.67–0.90). Results were consistent in the two strata, by the different types of thrombolytics and across various time intervals from symptom onset to treatment.
Conclusion: In STEMI patients treated with thrombolytic agents (predominantly streptokinase), fondaparinux significantly reduced the risk of death, re-MI and severe bleeds.
Key Words: Acute myocardial infarction • Thrombolytic therapy • Antithrombotic therapy