Author + information
- Received February 25, 2004
- Revision received June 7, 2004
- Accepted June 14, 2004
- Published online September 15, 2004.
- 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*
- ↵*Reprint requests and correspondence:
Dr. A. Michael Lincoff, The Cleveland Clinic Foundation, 9500 Euclid Avenue, Desk F25, Cleveland, Ohio 44195
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.
Supported by The Medicines Company. See reference 5 for a list of the investigators.
- Received February 25, 2004.
- Revision received June 7, 2004.
- Accepted June 14, 2004.
- American College of Cardiology Foundation