REVERSE-IT: Interim analysis shows promising effect of bentracimab on ticagrelor reversal

Bentracimab delivered immediate and sustained reversal of ticagrelor’s antiplatelet effect in patients undergoing invasive procedures or experiencing major bleeding. In addition, effective haemostasis rates were good or excellent in >90% of participants in the REVERSE-IT trial. Thus, bentracimab appears to be a promising option for ticagrelor reversal [1].

Ticagrelor is an oral P2Y₁₂ inhibitor for patients with acute coronary syndromes. Dr Deepak Bhatt (Brigham and Women’s Hospital, MA, USA) explained that antiplatelet drugs like ticagrelor are associated with spontaneous bleeding and surgery-related bleeding. In addition, the antiplatelet effects of ticagrelor cannot be reversed by platelet transfusion. Instead, a fast-acting reversal agent is needed to reverse ticagrelor’s mechanism of action.

Bentracimab is an intravenous monoclonal antibody, which has demonstrated swift and sustained reversal of ticagrelor’s antiplatelet effects in healthy individuals [2]. The multicentre, open-label, prospective, single-arm, phase 3 REVERSE-IT trial (NCT04286438) assessed the efficacy of bentracimab on reversing ticagrelor in patients who require urgent surgery or experience major bleeding. The current interim analysis’ primary reversal endpoint was the minimum percentage inhibition of P2Y₁₂ reaction units (PRU) within 4 hours. In total, 122 surgical patients and 7 bleeding patients were included in the reversal analysis.

The minimum percentage inhibition of PRU within 4 hours after bentracimab infusion was significantly lower than pre-dose PRU inhibition levels (P<0.001). The inhibitive effect of bentracimab on ticagrelor was significant as soon as 5–10 minutes after administration. The VASP platelet reactivity index (PRI) confirmed these results. The reversal effect was similar across surgical and bleeding patients. Moreover, the predefined subgroups benefitted equally from the bentracimab intervention. Adjudicated haemostasis within 24 hours was achieved in 100% of the analysed surgical patients and 77.8% of the bleeding patients. The results were consistent across subgroups. P-selectin levels or mean platelet volumes did not show platelet rebound activity. Correspondingly, none of the thrombotic events that occurred during the trial were attributed to bentracimab therapy.

Although this study did not have a control arm and the number of bleeding patients was low, the current interim analysis of the REVERSE-IT trial supported bentracimab as a promising agent for ticagrelor reversal. The enrolment of additional patients with bleeding is ongoing.

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   1. Bhatt DL, et al. REVERSE-IT: Effect of Bentracimab on Platelet Inhibition and Hemostasis in Patients on Ticagrelor with Major Bleeding or Requiring Urgent Procedures. LBS07, AHA 2021 Scientific Sessions, 13–15 November.
   2. Bhatt DL, et al. N Engl J Med. 2019;380:1825-1833.

 

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Posted on 14 January, 202222 February, 2024