HOME SUBSCRIPTIONS CURRENT ISSUE PAST ISSUES CARDIOSOURCE SEARCH HELP FEEDBACK		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Figures Only Full Text Full Text (PDF) All Versions of this Article: j.jacc.2007.07.042v1 50/18/1742    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (5) Citing Articles via Google Scholar Google Scholar Articles by Mehta, S. R. Articles by Yusuf, S. Search for Related Content PubMed Articles by Mehta, S. R. Articles by Yusuf, S.

CLINICAL RESEARCH: CLINICAL TRIAL

Efficacy and Safety of Fondaparinux Versus Enoxaparin in Patients With Acute Coronary Syndromes Undergoing Percutaneous Coronary Intervention

Results From the OASIS-5 Trial

Shamir R. Mehta, MD, MSc, FACC^_*,1,2,_*, Christopher B. Granger, MD, FACC^,1, John W. Eikelboom, MD, MSc^_*,1, Jean-Pierre Bassand, MD, FACC^,1, Lars Wallentin, MD, PhD^,3, David P. Faxon, MD, FACC^||,1, Ron J.G. Peters, MD^¶,1, Andrzej Budaj, MD^_**,1, Rizwan Afzal, MSc^_*, Susan Chrolavicius, BSc^_*, Keith A.A. Fox, MBChB, FRCP^,1 and Salim Yusuf, DPhil, FRCPC, FACC^_*,1

^_* 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.

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

This article has been cited by other articles:

				R. P. Giugliano and E. Braunwald The Year in Non-ST-Segment Elevation Acute Coronary Syndrome J. Am. Coll. Cardiol., September 23, 2008; 52(13): 1095 - 1103. [Full Text] [PDF]

				S. R. Dixon, C. L. Grines, and W. W. O'Neill The year in interventional cardiology. J. Am. Coll. Cardiol., June 17, 2008; 51(24): 2355 - 2369. [Full Text] [PDF]

				A. G.G. Turpie Selective factor Xa inhibition with fondaparinux: from concept to clinical benefit Eur. Heart J. Suppl., April 1, 2008; 10(suppl_C): C1 - C7. [Abstract] [Full Text] [PDF]

				S. R. Mehta Clinical benefit and practical use of fondaparinux in the invasive management of patients with acute coronary syndromes Eur. Heart J. Suppl., April 1, 2008; 10(suppl_C): C14 - C21. [Abstract] [Full Text] [PDF]

				J. Sanz, P. R. Moreno, and V. Fuster The year in atherothrombosis. J. Am. Coll. Cardiol., March 4, 2008; 51(9): 944 - 955. [Full Text] [PDF]

				A. N. DeMaria, J. J. Bax, O. Ben-Yehuda, P. Clopton, G. K. Feld, G. S. Ginsburg, B. H. Greenberg, J. D. Knoke, W. Y.W. Lew, J. A.C. Lima, et al. Highlights of the year in JACC 2007. J. Am. Coll. Cardiol., January 29, 2008; 51(4): 490 - 512. [Full Text] [PDF]