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(Circulation. 2005;111:1390-1397.)
© 2005 American Heart Association, Inc.

Interventional Cardiology

Randomized, Blinded Trial Comparing Fondaparinux With Unfractionated Heparin in Patients Undergoing Contemporary Percutaneous Coronary Intervention

Arixtra Study in Percutaneous Coronary Intervention: A Randomized Evaluation (ASPIRE) Pilot Trial

Shamir R. Mehta, MD, MSc; Philippe Gabriel Steg, MD; Christopher B. Granger, MD; Jean-Pierre Bassand, MD; David P. Faxon, MD; Jeffrey I. Weitz, MD; Rizwan Afzal, MSc; Bonnie Rush; Ron J.G. Peters, MD; Madhu K. Natarajan, MD; James L. Velianou, MD; David M. Goodhart, MD; Marino Labinaz, MD; Jean-Francois Tanguay, MD; Keith A.A. Fox, MBChB; Salim Yusuf, DPhil, for the ASPIRE Investigators^*

From McMaster University and the Population Health Research Institute (S.R.M., J.L.W., R.A., B.R., M.K.N., J.L.V., S.Y.), Hamilton Health Sciences, Hamilton, Canada; Hôpital Bichat (P.G.S.), Paris, France; Duke Clinical Research Institute (C.B.G.), Durham, NC; Centre Hospitalier Universitaire Jean Minjoz (J.-P.B.), Besancon, France; University of Chicago (D.P.F.), Chicago, Ill; Academic Medical Center (R.J.G.P.), Amsterdam, the Netherlands; Foothills Medical Center (D.M.G.), Calgary, Canada; Ottawa Heart Institute (M.L.), Ottawa, Canada; Montreal Heart Institute (J.-F.T.), Montreal, Canada; and the Royal Infirmary (K.A.A.F.), Edinburgh, Scotland.

Correspondence to Dr Shamir R. Mehta, Interventional Cardiology, Hamilton Health Sciences, General Division, 237 Barton St E, Hamilton, Ontario, Canada L6K 1B8. E-mail smehta{at}mcmaster.ca

Received July 19, 2004; revision received December 13, 2004; accepted December 21, 2004.

Background— Factor Xa plays a central role in the generation of thrombin, making it a novel target for treatment of arterial thrombosis. Fondaparinux is a synthetic factor Xa inhibitor that has been shown to be superior to standard therapies for the prevention of venous thrombosis. We performed a randomized trial to determine the safety and feasibility of fondaparinux in the percutaneous coronary intervention (PCI) setting.

Methods and Results— A total of 350 patients undergoing elective or urgent PCI were randomized in a blinded manner to receive unfractionated heparin (UFH), 2.5 mg fondaparinux IV, or 5.0 mg fondaparinux IV. Randomization was stratified for planned or no planned use of glycoprotein (GP) IIb/IIIa antagonists. The primary safety outcome was total bleeding, which was a combination of major and minor bleeding events. The incidence of total bleeding was 7.7% in the UFH group and 6.4% in the combined fondaparinux groups (hazard ratio, 0.81; 95% confidence interval, 0.35 to 1.84; P=0.61). Bleeding was less common in the 2.5-mg fondaparinux group compared with the 5-mg fondaparinux group (3.4% versus 9.6%, P=0.06). The composite efficacy outcome of all-cause mortality, myocardial infarction, urgent revascularization, or need for a bailout GPIIb/IIIa antagonist was 6.0% in the UFH group and 6.0% in the fondaparinux group, with no significant difference in efficacy among the fondaparinux doses compared with UFH. Coagulation marker analysis at 6 and 12 hours after PCI demonstrated that fondaparinux was superior to UFH in inducing a sustained reduction in markers of thrombin generation, as measured by prothrombin fragment F1.2 (P=0.02).

Conclusions— In this pilot study of patients undergoing contemporary PCI, factor Xa inhibition with the synthetic anticoagulant fondaparinux in doses of 2.5 and 5.0 mg was comparable to UFH for clinical safety and efficacy outcomes. These data form the basis for further evaluation of fondaparinux in arterial thrombosis.

Key Words: angioplasty • stents • anticoagulants • complications

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