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REPLACE-2 Randomized Trial

A. Michael Lincoff, MD; Neal S. Kleiman, MD; Dean J. Kereiakes, MD; Frederick Feit, MD; John A. Bittl, MD; J. Daniel Jackman, MD; Ian J. Sarembock, MB, ChB; David J. Cohen, MD; Douglas Spriggs, MD; Ramin Ebrahimi, MD; Gadi Keren, MD; Jeffrey Carr, MD; Eric A. Cohen, MD; Amadeo Betriu, MD; Walter Desmet, MD; Wolfgang Rutsch, MD; Robert G. Wilcox, MD; Pim J. de Feyter, MD; Alec Vahanian, MD; Eric J. Topol, MD; for the REPLACE-2 Investigators

JAMA. 2004;292:696-703.

Context  In the Randomized Evaluation in PCI Linking Angiomax to Reduced Clinical Events (REPLACE)-2 trial, bivalirudin with provisional glycoprotein IIb/IIIa (Gp IIb/IIIa) inhibition was found to be noninferior to heparin plus planned Gp IIb/IIIa blockade in the prevention of acute ischemic end points and was associated with significantly less bleeding by 30 days after percutaneous coronary intervention (PCI).

Objective  To determine whether the efficacy of bivalirudin remains comparable with that of heparin plus Gp IIb/IIIa blockade over 6 months and 1 year.

Design, Setting, and Participants  Follow-up study to 1 year of a randomized, double-blind trial conducted among 6010 patients undergoing urgent or elective PCI at 233 community or referral hospitals in 9 countries from October 2001 through August 2002.

Interventions  Patients were randomly assigned to receive intravenously bivalirudin (0.75 mg/kg bolus, 1.75 mg/kg per hour for the duration of PCI), with provisional Gp IIb/IIIa inhibition, or to receive heparin (65 U/kg bolus), with planned Gp IIb/IIIa inhibition (abciximab or eptifibatide). Both groups received daily aspirin and a thienopyridine for at least 30 days after PCI.

Main Outcome Measures  Incidence of death, myocardial infarction, or repeat revascularization by 6 months and death by 12 months after enrollment.

Results  At 6 months, death occurred in 1.4% of patients in the heparin plus Gp IIb/IIIa group and in 1.0% of patients in the bivalirudin group (hazard ratio [HR], 0.70; 95% confidence interval [CI], 0.43-1.14; P = .15). Myocardial infarction occurred in 7.4% and 8.2% of patients, respectively (HR, 1.12; 95% CI, 0.93-1.34; P = .24), and repeat revascularization was required in 11.4% and 12.1% of patients, respectively (HR, 1.06; 95% CI, 0.91-1.23; P = .45). By 1 year, death occurred in 2.46% of patients treated with heparin plus Gp IIb/IIIa blockade and in 1.89% of patients treated with bivalirudin (HR, 0.78; 95% CI, 0.55-1.11; P = .16). Nonsignificant trends toward lower 1-year mortality with bivalirudin were present in all patient subgroups analyzed and were of greatest magnitude among high-risk patients.

Conclusion  Long-term clinical outcome with bivalirudin and provisional Gp IIb/IIIa blockade is comparable with that of heparin plus planned Gp IIb/IIIa inhibition during contemporary PCI.

Author Affiliations: Cleveland Clinic Foundation, Cleveland, Ohio (Drs Lincoff and Topol); Baylor College of Medicine and Methodist Hospital, Houston (Dr Kleiman); the Lindner Center, Ohio Heart Health Center, Cincinnati (Dr Kereiakes); New York University School of Medicine, New York (Dr Feit); Ocala Heart Institute, Munroe Regional Medical Center, Ocala, Fla, (Dr Bittl); Tyler Cardiovascular Consultants/Trinity Mother Frances Hospital, Tyler, Tex (Dr Jackman); University of Virginia Health System, Charlottesville, Va (Dr Sarembock); Beth Israel Deaconess Medical Center, Boston, Mass (Dr D. J. Cohen); Clearwater Cardiovascular Consultants, Clearwater, Fla (Dr Spriggs); West Los Angeles VA, Los Angeles, Calif (Dr Ebrahimi); Tel Aviv Sourasky Medical Center, Tel Aviv, Israel (Dr Keren); East Texas Medical Center, Tyler (Dr Carr); Sunnybrook & Women's College Health Sciences Center, Toronto, Ontario (Dr E. A. Cohen); University of Barcelona Hospital Clinic, Barcelona, Spain (Dr Betriu); University Hospital Gasthuisberg, Leuven, Belgium (Dr Desmet); University Clinic Charite Berlin, Berlin, Germany (Dr Rutsch); University Hospital Nottingham, Nottingham, England (Dr Wilcox); University Hospital Dijkzigt, Rotterdam, the Netherlands (Dr de Feyter); and Hopital Bichat, Paris, France (Dr Vahanian).

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