Randomized Evaluation of PCI Linking Angiomax to Reduced Clinical Events - REPLACE 2 Long-Term Follow-up

Description:

The goal of the REPLACE 2 long-term follow-up study was to determine if there was a clinical benefit at six-month follow-up between the use of bivalirudin and unfractionated heparin (UFH) with planned glycoprotein (GP) IIb/IIIa inhibitor use during elective or urgent percutaneous coronary intervention (PCI).

Study Design

Study Design:

Patients Enrolled: 6,010
Mean Follow Up: 6 months; mortality through 1 year
Mean Patient Age: mean age 63 years
Female: 25%

Patient Populations:

Age >21 years and planned to undergo PCI with an approved device

Exclusions:

Primary or rescue PCI for acute MI; UFH within six hours; low molecular weight heparin within eight hours; or platelet count <100,000

Primary Endpoints:

Death, MI, urgent revascularization, and any revascularization at six months

Drug/Procedures Used:

Patients were randomized to UFH (65 U/kg bolus) with planned GP IIb/IIIa inhibitor use (abciximab or eptifibatide) during PCI or bivalirudin (0.75 mg/kg bolus and 1.75 mg/kg/h infusion during the PCI) and provisional GP IIb/IIIa use (abciximab or eptifibatide) during PCI. The primary endpoint of the trial was the quadruple composite of death, MI, severe ischemia requiring urgent revascularization by 30 days, or in-hospital major bleed.

Patients were also followed for death, MI, urgent revascularization, or any revascularization through six months. Mortality data will be collected through one year. Data were analyzed for superiority of bivalirudin over UFH + GP IIb/IIIa, not noninferiority, as was done with the 30-day analysis.

Concomitant Medications:

Aspirin; clopidogrel pretreatment at investigator discretion

Principal Findings:

One year follow-up was complete in 98.6% of patients in the UFH + GP IIb/IIIa arm and 98.4% of patients in the bivalirudin arm. There was no difference between the bivalirudin arm and the UFH + GP IIb/IIIa arm in six-month death (1.4% vs. 1.0%, p=0.15), myocardial infarction (MI) (7.4% vs. 8.2%, p=0.24), or revascularization (11.4% vs. 12.1%, p=0.45 for UFH + GP IIb/IIIa arm vs. bivalirudin arm, respectively). The composite endpoint of death, MI or revascularization was 17.5% in the UFH + GP IIb/IIIa arm vs. 18.8% in the bivalirudin arm (hazard ratio [HR} 1.11, p=0.10). Mortality by 1 year was 2.46% in the UFH + GP IIb/IIIa arm vs. 1.89% in the bivalirudin arm (p=0.16).

During the 31-180 day follow-up period, there were 34 MIs in the UFH + GP IIb/IIIa arm and 35 in the bivalirudin arm. Cardiovascular deaths comprised 57% of the deaths in the bivalirudin arm and 60% of the deaths in the GP IIb/IIIa arm.

Interpretation:

Among patients undergoing planned PCI, there was no significant difference in the individual endpoints of six-month mortality, MI, or revascularization between treatment with UFH with planned GP IIb/IIIa inhibitor use or bivalirudin but the composite of the 3 endpoints trended lower in the GP IIb/IIIa arm. The trend toward a nonsignificant increase in the MI rate was maintained at six months, but there was no additional increase in MIs during the 31-180 day follow-up period.

Unlike the 30-day data that were analyzed for noninferiority, the six-month data were analyzed for superiority.

References:

Lincoff, et al. Long-term Efficacy of Bivalirudin and Provisional Glycoprotein IIb/IIIa Blockade vs Heparin and Planned Glycoprotein IIb/IIIa Blockade During Percutaneous Coronary Revascularization. JAMA. 2004;292:696-703.

Presented at the 2003 Transcatheter Cardiovascular Therapeutics conference, by A. Michael Lincoff, MD

Clinical Topics: Anticoagulation Management, Heart Failure and Cardiomyopathies, Invasive Cardiovascular Angiography and Intervention, Heart Failure and Cardiac Biomarkers

Keywords: Myocardial Infarction, Follow-Up Studies, Coronary Disease, Heparin, Immunoglobulin Fab Fragments, Platelet Membrane Glycoprotein IIb, Hirudins, Percutaneous Coronary Intervention, Recombinant Proteins, Peptide Fragments, Platelet Glycoprotein GPIIb-IIIa Complex


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