Reversal of Platelet Inhibition with Bentracimab

Arterial thrombosis formation is an important physiologic function to regulate and stop bleeding. However, arterial thrombosis can also lead to acute coronary syndrome and strokes. Activation of P2Y12 receptors on platelets results in thrombosis formation. Thus, medications that target the P2Y12 receptor (P2Y12 inhibitors) can reduce and prevent acute coronary artery syndrome and strokes.

The following two types of P2Y12 inhibitors are currently used: (1) ones that bind irreversibly to the receptor, leading to irreversible inhibition over the lifespan of the platelets (e.g., clopidogrel and prasugrel) and (2) ones that bind reversibly in a concentration-dependent fashion to the receptor, leading to reversible inhibition (e.g., ticagrelor). One concern with reversible P2Y12 inhibitors is in the context of bleeding: If an urgent platelet transfusion is required, the transfused platelets may be inhibited by the presence of an existing reversible P2Y12 inhibitor, which can lead to a poor hemostasis outcome. Bentracimab is a recombinant intravenous monoclonal neutralizing antibody that binds ticagrelor with high affinity and specificity and can reverse the antiplatelet effect of ticagrelor.

In a nonrandomized, single-arm, prospective study published in NEJM Evidence, researchers examined the effects of bentracimab in 150 ticagrelor-treated patients who required urgent surgery or an invasive procedure or had major bleeding. The primary reversal end point was the difference in percent inhibition of platelet function (as measured by P2Y12 reactivity units [PRU]) within 4 hours of bentracimab infusion) and the achievement of effective hemostasis.

Within 4 hours after bentracibmab infusion, researchers observed a significant 135% reduction in platelet inhibition (P <0.001). The reduction in platelet inhibition was maintained for up to 72 hours after infusion (P <0.001). Clinical hemostasis (as measured by the Global Use of Strategies to Open Occluded Coronary Arteries [GUSTO] bleeding scale) was achieved in 120 of 122 (98.4%) of patients analyzed, and was significantly higher than the hemostasis rate of 50% expected in a similar population not treated with a ticagrelor reversal agent. Adverse events on the same day or post-infusion were reported in 8 of 150 patients (5.3%), including myocardial infarction (3 patients), cerebrovascular event (3 patients), and lower extremity arterial thromboembolism (2 patients).

The results of this uncontrolled study show that the intravenous ticagrelor reversal agent bentracibmab can restore and maintain sustained platelet function for up to 72 hours.

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James Yeh, MD, MPH, is an internist and assistant in medicine at the Massachusetts General Hospital and an instructor in medicine at Harvard Medical School. His clinical and academic interests are in evidence-based medicine, medical education, continuing medical education, cardiopulmonary diseases, cardiovascular risk reduction, critical illness, care transition, polypharmacy, and health communication. He was a NEJM editorial fellow in 2015-2016.