REG1 with at least 50% reversal resulted in similar 30-day bleeding rates (30-35%) compared to heparin (31%) in ACS patients, whereas 25% reversal led to excess bleeding (65%).
RCT (n=640)
partially blinded
2:1:1:2:2
Does the REG1 system with variable anivamersen reversal safely provide anticoagulation and mitigate bleeding compared to heparin in NSTE-ACS patients undergoing early invasive management?
In NSTE-ACS patients undergoing early cardiac catheterization, at least 50% reversal of pegnivacogin with anivamersen is required to achieve bleeding rates comparable to heparin, though the trial was stopped early due to allergic-like reactions.
AIMS: We sought to determine the degree of anticoagulation reversal required to mitigate bleeding, and assess the feasibility of using pegnivacogin to prevent ischaemic events in acute coronary syndrome (ACS) patients managed with an early invasive approach. REG1 consists of pegnivacogin, an RNA aptamer selective factor IXa inhibitor, and its complementary controlling agent, anivamersen. REG1 has not been studied in invasively managed patients with ACS nor has an optimal level of reversal allowing safe sheath removal been defined. METHODS AND RESULTS: 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 ischaemia. Enrolment in the 25% reversal arm was suspended after 41 patients. Enrolment 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. Ischaemic events occurred in 3.0 and 5.7% of REG1 and heparin patients, respectively. CONCLUSION: At least 50% reversal is required to allow safe sheath removal after cardiac catheterization. REG1 appears a safe strategy to anticoagulate ACS patients managed invasively and warrants further investigation in adequately powered clinical trials of patients who require short-term high-intensity anticoagulation.
“While not adequately powered as a phase II study, our study supports the concept that controllable anticoagulation offers, for the first time, the possibility of favourably impacting both ischaemic and bleeding endpoints—or at minimum, developing a more potent anticoagulant without increasing bleeding risk. This is possible because the availability of a reversible agent allows safe targeting and achievement of very high levels of anticoagulation. This strategy may be extremely attractive not only in PCI, but in other invasive procedures (eg. coronary artery bypass grafting) or acute care settings where the need for anticoagulation may change significantly during the clinical care of a patient or transient high-level anticoagulation is needed.”
Povsic et al. (Thu,) conducted a rct in Non-ST-elevation acute coronary syndrome (n=640). REG1 (pegnivacogin and anivamersen) vs. heparin was evaluated on total ACUITY bleeding through 30 days. REG1 with at least 50% reversal resulted in similar 30-day bleeding rates (30-35%) compared to heparin (31%) in ACS patients, whereas 25% reversal led to excess bleeding (65%).