CLINICAL RESEARCH: CLINICAL TRIAL
Efficacy and Safety of Fondaparinux Versus Enoxaparin in Patients With Acute Coronary Syndromes Undergoing Percutaneous Coronary InterventionResults From the OASIS-5 Trial
Shamir R. Mehta, MD, MSc, FACC*,*,
Christopher B. Granger, MD, FACC ,
John W. Eikelboom, MD, MSc*,
Jean-Pierre Bassand, MD, FACC ,
Lars Wallentin, MD, PhD ,
David P. Faxon, MD, FACC||,
Ron J.G. Peters, MD¶,
Andrzej Budaj, MD**,
Rizwan Afzal, MSc*,
Susan Chrolavicius, BSc*,
Keith A.A. Fox, MBChB, FRCP and
Salim Yusuf, DPhil, FRCPC, FACC*
* Department of Medicine, McMaster University and Population Health Research Institute, Hamilton Health Sciences, Hamilton, Ontario, Canada
Duke Clinical Research Institute, Duke University, Durham, North Carolina
Centre Hospitalier Universitaire Jean Minjoz, Besançon, France
Department of Medical Sciences and Uppsala Clinical Research Centre, University Hospital, Uppsala, Sweden
|| Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts
¶ Academic Medical Centre, Amsterdam, the Netherlands
** Postgraduate Medical School, Department of Cardiology, Grochowski Hospital, Warsaw, Poland
Royal Infirmary and University of Edinburgh, Edinburgh, Scotland
Manuscript received May 21, 2007;
revised manuscript received July 30, 2007,
accepted July 31, 2007.
* Reprint requests and correspondence: Dr. Shamir R. Mehta, Interventional Cardiology, Hamilton Health Sciences, General Division, McMaster Clinic Room 508, 237 Barton Street East, Hamilton, ON L8L 2X2, Canada. (Email: smehta{at}mcmaster.ca).
Objectives: This study reports a prospectively planned analysis of patients with acute coronary syndrome who underwent early percutaneous coronary intervention (PCI) in the OASIS-5 (Fifth Organization to Assess Strategies in Ischemic Syndromes) trial.
Background: In the OASIS-5 trial, fondaparinux was similar to enoxaparin for short-term efficacy, but reduced major bleeding by one-half and 30-day mortality by 17%.
Methods: The OASIS-5 trial was a double-blind, randomized comparison of fondaparinux and enoxaparin in 20,078 patients with acute coronary syndrome. A total of 12,715 patients underwent heart catheterization during the initial hospitalization, and 6,238 patients underwent PCI. In the fondaparinux group, intravenous fondaparinux was given for PCI. In the enoxaparin group, no additional anticoagulant was given if PCI was <6 h from last subcutaneous dose, and additional intravenous unfractionated heparin (UFH) was given if PCI was >6 h.
Results: Fondaparinux compared with enoxaparin reduced major bleeding by more than one-half (2.4% vs. 5.1%, hazard ratio [HR] 0.46, p < 0.00001) at day 9, with similar rates of ischemic events, resulting in superior net clinical benefit (death, myocardial infarction, stroke, major bleeding: 8.2% vs. 10.4%, HR 0.78, p = 0.004). Fondaparinux reduced major bleeding 48 h after PCI irrespective of whether PCI was performed <6 h of the last enoxaparin dose (1.6% vs. 3.8%, HR 0.42, p < 0.0001) or >6 h when UFH was given (1.3% vs. 3.4%, HR 0.39, p < 0.0001). Catheter thrombus was more common in patients receiving fondaparinux (0.9%) than enoxaparin alone (0.4%), but was largely prevented by using UFH at the time of PCI, without any increase in bleeding.
Conclusions: Upstream therapy with fondaparinux compared with upstream enoxaparin substantially reduces major bleeding while maintaining efficacy, resulting in superior net clinical benefit. The use of standard UFH in place of fondaparinux at the time of PCI seems to prevent angiographic complications, including catheter thrombus, without compromising the benefits of upstream fondaparinux.
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Abbreviations and Acronyms
| | ACS = acute coronary syndrome | | ACT = activated clotting time | | CI = confidence interval | | GP = glycoprotein | | HR = hazard ratio | | MI = myocardial infarction | | PCI = percutaneous coronary intervention | | RR = relative risk | | UFH = unfractionated heparin |
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