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).
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.
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.
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.
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.