This Article Figures Only Full Text Full Text (PDF) 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 PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Saw, J. Search for Related Content PubMed PubMed Citation Articles by Saw, J.

INTERVENTIONAL CARDIOLOGY

Lack of clopidogrel pretreatment effect on the relative efficacy of bivalirudin with provisional glycoprotein IIb/IIIa blockade compared to heparin with routine glycoprotein IIb/IIIa blockade

A REPLACE-2 substudy

Jacqueline Saw, MD^*, A. Michael Lincoff, MD^*,*, Walter DeSmet, MD, Amadeo Betriu, MD, Wolfgang Rutsch, MD, Robert G. Wilcox, MD^||, Neil S. Kleiman, MD^¶, Kathy Wolski, MPH^*, Eric J. Topol, MD^* REPLACE-2 Investigators^*

^* Department of Cardiovascular Medicine, the Cleveland Clinic Foundation, Cleveland, Ohio, USA
University Hospital Gasthuisberg, Leuven, Belgium
Hospital Clinic, University of Barcelona, Barcelona, Spain
Universitätsmedizin Berlin, Berlin, Germany
^|| University Hospital Nottingham, Nottingham, United Kingdom
^¶ Baylor College of Medicine, Houston, Texas, USA

Manuscript received February 25, 2004; revised manuscript received June 7, 2004, accepted June 14, 2004.

^* Reprint requests and correspondence: Dr. A. Michael Lincoff, The Cleveland Clinic Foundation, 9500 Euclid Avenue, Desk F25, Cleveland, Ohio 44195 (Email: lincofa{at}ccf.org).

OBJECTIVES: The purpose of this study was to assess if clopidogrel pretreatment affects the relative efficacy of bivalirudin versus heparin with glycoprotein (GP) IIb/IIIa blockade for percutaneous coronary interventions (PCI).

BACKGROUND: Although thienopyridine pretreatment may improve clinical outcomes with PCI, it is unknown if bivalirudin's efficacy compared with heparin is dependent upon such pretreatment.

METHODS: The Randomized Evaluation in Percutaneous coronary intervention Linking Angiomax to reduced Clinical Events (REPLACE-2) trial was a double-blind, triple-dummy, randomized-controlled trial comparing heparin plus routine GP IIb/IIIa blockade (heparin group) with bivalirudin plus provisional GP IIb/IIIa blockade (bivalirudin group) during PCI. The primary end point was a composite of death, myocardial infarction (MI), urgent revascularization at 30 days, and major in-hospital bleeding. The secondary end point was a 30-day composite of death, MI, and urgent revascularization. Clopidogrel pretreatment was encouraged (300 mg loading, 75 mg/day).

RESULTS: Of 6,010 patients enrolled, 5,893 received clopidogrel, with 85.8% in the bivalirudin and 84.6% in the heparin group receiving clopidogrel pretreatment. Bivalirudin (provisional GP IIb/IIIa blockade 7.2%) was noninferior to the heparin group for both primary and secondary end points. Clopidogrel pretreatment did not affect the relative efficacy of bivalirudin versus heparin with GP IIb/IIIa blockade, irrespective of pretreatment duration. Pretreatment was associated with significantly lower primary end point with bivalirudin (8.7% pretreatment vs. 12.9% no pretreatment, p = 0.007), and nonsignificantly with heparin (9.7% vs. 11.7%, respectively, p = 0.20). Multivariable models showed a trend toward lower primary and secondary end points with clopidogrel pretreatment.

CONCLUSIONS: Clopidogrel pretreatment at the doses and time administered in this trial did not influence the relative efficacy of bivalirudin versus heparin plus GP IIb/IIIa blockade for PCI. However, pretreatment was associated with a trend towards lower clinical events after PCI.

Abbreviations and Acronyms   GP = glycoprotein   MI = myocardial infarction   OR = odds ratio   PCI = percutaneous coronary intervention   REPLACE-2 = Randomized Evaluation in Percutaneous coronary intervention Linking Angiomax to reduced Clinical Events

This article has been cited by other articles:

				A. M. Lincoff, S. R. Steinhubl, S. V. Manoukian, D. Chew, C. V. Pollack Jr, F. Feit, J. H. Ware, M. E. Bertrand, E. M. Ohman, W. Desmet, et al. Influence of Timing of Clopidogrel Treatment on the Efficacy and Safety of Bivalirudin in Patients With Non-ST-Segment Elevation Acute Coronary Syndromes Undergoing Percutaneous Coronary Intervention: An Analysis of the ACUITY (Acute Catheterization and Urgent Intervention Triage strategY) Trial J. Am. Coll. Cardiol. Intv., December 1, 2008; 1(6): 639 - 648. [Abstract] [Full Text] [PDF]

				J. Herrmann Peri-procedural myocardial injury: 2005 update Eur. Heart J., December 1, 2005; 26(23): 2493 - 2519. [Abstract] [Full Text] [PDF]

				D. J. Moliterno and S. R. Steinhubl Clopidogrel for Percutaneous Coronary Revascularization: Time for More Pretreatment, Retreatment, or Both? JAMA, September 14, 2005; 294(10): 1271 - 1273. [Full Text] [PDF]

				M. S. Sabatine, C. P. Cannon, C. M. Gibson, J. L. Lopez-Sendon, G. Montalescot, P. Theroux, B. S. Lewis, S. A. Murphy, C. H. McCabe, E. Braunwald, et al. Effect of Clopidogrel Pretreatment Before Percutaneous Coronary Intervention in Patients With ST-Elevation Myocardial Infarction Treated With Fibrinolytics: The PCI-CLARITY Study JAMA, September 14, 2005; 294(10): 1224 - 1232. [Abstract] [Full Text] [PDF]

				M. Di Nisio, S. Middeldorp, and H. R. Buller Direct Thrombin Inhibitors N. Engl. J. Med., September 8, 2005; 353(10): 1028 - 1040. [Full Text] [PDF]

				R. P. Giugliano and E. Braunwald The Year in Non--ST-Segment Elevation Acute Coronary Syndromes J. Am. Coll. Cardiol., September 6, 2005; 46(5): 906 - 919. [Full Text] [PDF]