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The OASIS-6 Randomized Trial

The OASIS-6 Trial Group*

JAMA. 2006;295:1519-1530. Published online March 14, 2006 (doi:10.1001/jama.295.13.joc60038).

Context  Despite many therapeutic advances, mortality in patients with acute ST-segment elevation myocardial infarction (STEMI) remains high. The role of additional antithrombotic agents is unclear, especially among patients not receiving reperfusion therapy.

Objective  To evaluate the effect of fondaparinux, a factor Xa inhibitor, when initiated early and given for up to 8 days vs usual care (placebo in those in whom unfractionated heparin [UFH] is not indicated [stratum 1] or unfractionated heparin for up to 48 hours followed by placebo for up to 8 days [stratum 2]) in patients with STEMI.

Design, Setting, and Participants  Randomized double-blind comparison of fondaparinux 2.5 mg once daily or control for up to 8 days in 12 092 patients with STEMI from 447 hospitals in 41 countries (September 2003-January 2006). From day 3 through day 9, all patients received either fondaparinux or placebo according to the original randomized assignment.

Main Outcome Measures  Composite of death or reinfarction at 30 days (primary) with secondary assessments at 9 days and at final follow-up (3 or 6 months).

Results  Death or reinfarction at 30 days was significantly reduced from 677 (11.2%) of 6056 patients in the control group to 585 (9.7%) of 6036 patients in the fondaparinux group (hazard ratio [HR], 0.86; 95% confidence interval [CI], 0.77-0.96; P = .008); absolute risk reduction, 1.5%; 95% CI, 0.4%-2.6%). These benefits were observed at 9 days (537 [8.9%] placebo vs 444 [7.4%] fondaparinux; HR, 0.83; 95% CI, 0.73-0.94; P = .003, and at study end (857 [14.8%] placebo vs 756 [13.4%] fondaparinux; HR, 0.88; 95% CI, 0.79-0.97; P = .008). Mortality was significantly reduced throughout the study. There was no heterogeneity of the effects of fondaparinux in the 2 strata by planned heparin use. However, there was no benefit in those undergoing primary percutaneous coronary intervention. In other patients in stratum 2, fondaparinux was superior to unfractionated heparin in preventing death or reinfarction at 30 days (HR, 0.82; 95% CI, 0.66-1.02; P = .08) and at study end (HR, 0.77; 95% CI, 0.64-0.93; P = .008). Significant benefits were observed in those receiving thrombolytic therapy (HR, 0.79; P = .003) and those not receiving any reperfusion therapy (HR, 0.80; P = .03). There was a tendency to fewer severe bleeds (79 for placebo vs 61 for fondaparinux; P = .13), with significantly fewer cardiac tamponade (48 vs 28; P = .02) with fondaparinux at 9 days.

Conclusion  In patients with STEMI, particularly those not undergoing primary percutaneous coronary intervention, fondaparinux significantly reduces mortality and reinfarction without increasing bleeding and strokes.

Trial Registration  ClinicalTrials.gov Identifier NCT00064428

*Authors and Writing Committee: Salim Yusuf, DPhil, FRCPC, FRSC, Shamir R. Mehta, MD, MSc, FRCPC, Susan Chrolavicius, RN, BA, Rizwan Afzal, MSc, and Janice Pogue, MSc (Department of Medicine, McMaster University and Hamilton Health Sciences, Hamilton, Ontario); Christopher B. Granger, MD (Division of Cardiology, Duke University, Durham, NC); Andrzej Budaj, MD, PhD (Division of Cardiology, Grochowski Hospital, Warsaw, Poland); Ron J. G. Peters, MD (Division of Cardiology, University of Amsterdam, Amsterdam, the Netherlands); Jean-Pierre Bassand, MD, FESC (Division of Cardiology, University of Besancon, Besancon, France); Lars Wallentin, MD, PhD (Division of Cardiology, Uppsala University, Uppsala, Sweden); Campbell Joyner, MD, FRCPC (Division of Cardiology, University of Toronto and Sunnybrook Hospital, Toronto); and Keith A. A. Fox, MB, ChB, FRCP (Cardiovascular Research Division, University of Edinburgh, Edinburgh, Scotland).

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