REPLACE-1: The Randomized Evaluation of PCI Linking ANGIOMAX to Reduced Clinical Events part 1¹

• Summary
• Trial Design
• Clinical Outcomes

Summary

• The results of REPLACE-1 are consistent with prior randomized studies of Angiomax® (bivalirudin) in demonstrating reductions in ischemic events and major hemorrhagic events versus heparin
• The results of REPLACE-1 demonstrate a nonstatistically different 19% reduction in ischemic and hemorrhagic events in patients treated with ANGIOMAX versus heparin (7.1% vs 8.8%, respectively)
• This trial supports the safety and efficacy of ANGIOMAX administered concomitantly with glycoprotein (GP) IIb/IIIa inhibitors

Trial Design

The Randomized Evaluation of PCI Linking ANGIOMAX to Reduced Clinical Events trial part 1 (REPLACE-1) was an open-label randomized study of 1056 patients undergoing percutaneous coronary intervention (PCI) comparing ANGIOMAX (0.75 mg/kg bolus, 1.75 mg/kg/h infusion for the duration of the procedure and up to 4 hours postprocedure at investigator discretion) to heparin administered according to institutional practice (65-80 U/kg initial bolus).

All patients received aspirin and 56% received clopidogrel. Overall, 758 (72%) of patients received a GP IIb/IIIa inhibitor according to institutional practice. Stents were placed in 84.1% of heparin-treated patients and 86.2% of patients treated with ANGIOMAX.

Indications for PCI included unstable angina (45%), myocardial infarction (MI) within 7 days prior to intervention (8.6%), and stable angina (22%).

Clinical End points: The primary end point was a composite end point of the occurrence of death, MI, urgent revascularization, and major bleeding at 48 hours (or time of hospital discharge if earlier).

Clinical Outcomes

A total of 1056 patients from 77 US clinical sites were enrolled in REPLACE-1 with 524 patients randomized to heparin and 532 patients randomized to ANGIOMAX. The median age was 65 years and 70% of the patients were male.

48-Hour End points in REPLACE-1

* Major bleeding defined as intracranial, intraocular, or retroperitoneal hemorrhage or clinically overt bleeding resulting in a decrease in hemoglobin by >3 g/dL or transfusion >2 U of blood.

There were no significant differences in any of the individual end points or in the composite end points.

Major hemorrhage was reduced by 22% in the ANGIOMAX group (2.1% vs. 2.7% of patients in the heparin group, P = .052), despite significant use of GP IIb/IIIa.

Safety Considerations

ANGIOMAX with provisional use of glycoprotein IIb/IIIa inhibitor is indicated for use as an anticoagulant in patients undergoing percutaneous coronary intervention (PCI), and in patients with or at risk for heparin-induced thrombocytopenia and thrombosis syndrome (HIT/HITTS) undergoing PCI. ANGIOMAX is intended for use with aspirin and has been studied only in patients receiving concomitant aspirin. ANGIOMAX is contraindicated in patients with active major bleeding or hypersensitivity to ANGIOMAX or its components. The most common (10%) adverse events for ANGIOMAX were back pain, pain, nausea, headache, and hypotension. An unexplained fall in blood pressure or hematocrit, or any unexplained symptom, should lead to serious consideration of a hemorrhagic event and cessation of ANGIOMAX administration. Please see complete prescribing information.