Long-term Efficacy of Bivalirudin and Provisional Glycoprotein IIb/IIIa Blockade vs Heparin and Planned Glycoprotein IIb/IIIa Blockade During Percutaneous Coronary Revascularization<SUBTITLE>REPLACE-2 Randomized Trial</SUBTITLE>

Abstract

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.