A Phase 2, Randomized, Partially Blinded, Active-Controlled Study Assessing the Efficacy and Safety of Variable Anticoagulation Reversal Using the REG1 System in Patients With Acute Coronary Syndromes: Results of the RADAR Trial
What is the degree of anticoagulation reversal required to mitigate bleeding, and the feasibility of using pegnivacogin (REG1) to prevent ischemic events in acute coronary syndrome (ACS) patients managed with an early invasive approach?
Non-ST-elevation ACS patients (n = 640) with planned early cardiac catheterization via femoral access were randomized 2:1:1:2:2 to pegnivacogin with 25%, 50%, 75%, or 100% anivamersen reversal or heparin. The primary endpoint was total ACUITY bleeding through 30 days. Secondary endpoints included major bleeding and the composite of death, myocardial infarction, urgent target vessel revascularization, or recurrent ischemia. Odds ratios and 95% confidence intervals were provided for the ischemic event composite (comparing REG1 with heparin) and for bleeding events (comparing REG1-100% reversal with heparin and REG1-100% reversal with REG1-25% reversal).
Enrollment in the 25% reversal arm was suspended after 41 patients. Enrollment was stopped after three patients experienced allergic-like reactions. Bleeding occurred in 65%, 34%, 35%, 30%, and 31% of REG1 patients with 25%, 50%, 75%, and 100% reversal and heparin. Major bleeding occurred in 20%, 11%, 8%, 7%, and 10% of patients. Ischemic events occurred in 3.0% and 5.7% of REG1 and heparin patients, respectively.
The authors concluded that REG1 appears to be a safe strategy to anticoagulate ACS patients managed invasively.
This study suggests that near complete inhibition of factor IXa with pegnivacogin, followed by anivamersen-mediated reversal, may provide a strategy that permits effective periprocedural anticoagulation without increased bleeding despite immediate post-procedure sheath removal. Furthermore, at least 50% pegnivacogin reversal is required to allow early sheath removal after cardiac catheterization via a femoral approach. Adequately powered randomized clinical trials are indicated to determine the safety and efficacy of factor IXa inhibition with REG1 compared with other anticoagulation strategies in patients who require high-intensity, short-term anticoagulation.
Keywords: Odds Ratio, Aptamers, Nucleotide, Acute Coronary Syndrome, Myocardial Infarction, Factor IXa, Cardiac Catheterization, Saccharomyces cerevisiae Proteins, Heparin, Blood Coagulation, Coronary Angiography, Confidence Intervals, Hemorrhage
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