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

Study Questions:

What is the feasibility of using pegnivacogin to prevent ischemic events and the degree of anticoagulation reversal required to mitigate bleeding in acute coronary syndrome (ACS) patients managed with an early invasive approach?

Methods:

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. REG1 consists of pegnivacogin, an RNA aptamer selective factor IXa inhibitor, and its complementary controlling agent, anivamersen. 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.

Results:

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.

Conclusions:

The authors concluded that REG1 appears to be a safe strategy to anticoagulate ACS patients managed invasively, and warrants further investigation.

Perspective:

This study reported that at least 50% pegnivacogin reversal is required to allow early sheath removal after cardiac catheterization via a femoral approach, and 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. Although REG1 appears to be a safe strategy to anticoagulate ACS patients managed invasively, adequately powered randomized clinical trials are warranted 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.

Clinical Topics: Acute Coronary Syndromes, Anticoagulation Management, Dyslipidemia, Anticoagulation Management and ACS, Lipid Metabolism, Novel Agents

Keywords: Aptamers, Nucleotide, Myocardial Infarction, Acute Coronary Syndrome, Cardiac Catheterization, Factor IXa, Heparin, Hemorrhage


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