This Article Full Text Full Text (PDF) Correction Correction (v118,pe842) All Versions of this Article: 118/20/2038    most recent CIRCULATIONAHA.108.789479v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Mehta, S. R. Search for Related Content PubMed PubMed Citation Articles by Mehta, S. R. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Medline Plus Health Information Blood Thinners Hazardous Substances DB HEPARIN Related Collections Arterial thrombosis Coagulation Heparin Other anticoagulants Acute coronary syndromes Related Article

(Circulation. 2008;118:2038-2046.)
© 2008 American Heart Association, Inc.

Coronary Heart Disease

Antithrombotic Therapy With Fondaparinux in Relation to Interventional Management Strategy in Patients With ST- and Non–ST-Segment Elevation Acute Coronary Syndromes

An Individual Patient–Level Combined Analysis of the Fifth and Sixth Organization to Assess Strategies in Ischemic Syndromes (OASIS 5 and 6) Randomized Trials

Shamir R. Mehta, MD, MSc; William E. Boden, MD; John W. Eikelboom, MD, MSc; Marcus Flather, MD; P. Gabriel Steg, MD; Alvaro Avezum, MD; Rizwan Afzal, MSc; Leopoldo S. Piegas, MD; David P. Faxon, MD; Petr Widimsky, MD; Andrzej Budaj, MD; Susan Chrolavicius, BScN; Hans-Jurgen Rupprecht, MD; Sanjit Jolly, MD; Christopher B. Granger, MD; Keith A.A. Fox, MBChB; Jean-Pierre Bassand, MD; Salim Yusuf, MBBS, DPhil, for the OASIS 5 and 6 Investigators

From McMaster University and the Population Health Research Institute, Hamilton Health Sciences, Hamilton, Ontario, Canada (S.R.M., J.W.E., S.C., S.J., S.Y.); University of Buffalo, Schools of Medicine and Public Health, Buffalo, NY (W.E.B.); Royal Brompton and Harefield NHS Trust, London, UK (M.F.); Hôpital Bichat-Claude Bernard, Paris, France (P.G.S.); Dante Pazzanese Institute of Cardiology, Saõ Paulo, Brazil (A.A., L.P.); Brigham and Women’s Hospital, Boston, Mass (D.P.F.); University Hospital Kralovske Vinohrady, Prague, Czech Republic (P.W.); Postgraduate Medical School, Grochowski Hospital, Warsaw, Poland (A.B.); Royal Infirmary of Edinburgh, University of Edinburgh, Edinburgh, UK (K.A.A.F.); Second Medical Clinic, Ruesselsheim, Germany (H.J.R.); Duke Clinical Research Institute, Durham, NC (C.B.G.); and University Hospital Jean Minjoz, Besançon, France (J.P.B.).

Correspondence to Shamir R. Mehta, MD, MSc, FRCPC, FACC, Hamilton Health Sciences, General Division, McMaster Clinic, Room 508, 237 Barton St E, Hamilton, Ontario, L8L 2X2, Canada. E-mail smehta{at}mcmaster.ca

Received April 30, 2008; accepted August 29, 2008.

Background— The Fifth and Sixth Organization to Assess Strategies in Ischemic Syndromes (OASIS 5 and 6) trials evaluated fondaparinux, a synthetic factor Xa inhibitor, in patients with non–ST- and ST-segment elevation acute coronary syndromes, respectively. Combined results for these 2 trials on major efficacy and safety outcomes and data on the effects of fondaparinux in relation to interventional management strategy have not been previously reported.

Methods and Results— We performed an individual patient–level combined analysis of 26 512 patients from the OASIS 5 and 6 trials who were randomized in a double-blind fashion to fondaparinux 2.5 mg daily or a heparin-based strategy (dose-adjusted unfractionated heparin or enoxaparin). Results were stratified according to whether an early invasive, a delayed invasive, or an initial conservative management strategy was performed. Fondaparinux was superior to heparin in reducing the composite of death, myocardial infarction, or stroke (8.0% versus 7.2%; hazard ratio [HR], 0.91; P=0.03) and death alone (4.3% versus 3.8%; HR, 0.89; P=0.05). Fondaparinux reduced major bleeding by 41% (3.4% versus 2.1%; HR, 0.59; P<0.00001) and had a more favorable net clinical outcome than heparin (11.1% versus 9.3%; HR, 0.83; P<0.0001). In 19 085 patients treated with an invasive strategy, fondaparinux suppressed ischemic events to an extent similar to heparin and reduced major bleeding by more than one-half, resulting in a superior net clinical outcome (10.8% versus 9.4%; HR, 0.87; P=0.008). A similar benefit also was observed in those treated with a conservative strategy (HR, 0.74; 95% confidence interval, 0.64 to 0.85; P<0.001).

Conclusion— Compared with a heparin-based strategy, fondaparinux reduced mortality, ischemic events, and major bleeding across the full spectrum of acute coronary syndromes and was associated with a more favorable net clinical outcome in patients undergoing either an invasive or a conservative management strategy.

---

 

CLINICAL PERSPECTIVE

Related Article:

Clinical Summaries
Circulation 2008 118: 2013-2014. [Extract] [Full Text]

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., October 13, 2009; 54(16): 1544 - 1555. [Full Text] [PDF]

				S. R. Dixon, C. L. Grines, and W. W. O'Neill The year in interventional cardiology. J. Am. Coll. Cardiol., June 2, 2009; 53(22): 2080 - 2097. [Full Text] [PDF]

				C. Rea and B. J Hunt Reducing vascular risk - venous thromboembolism and anticoagulation Clin Risk, May 1, 2009; 15(3): 90 - 92. [Full Text] [PDF]