REVERSE-IT: Bentracimab restores platelet function in ticagrelor users

The primary results of the REVERSE-IT trial showed that bentracimab restored platelet function and appeared to reverse the effects of ticagrelor in patients on ticagrelor who underwent urgent surgery or had major bleeding.

“Ticagrelor is an effective P2Y₁₂ inhibitor that is being used in patients with acute coronary syndromes, prior myocardial infarction, stroke, or transient ischaemic attacks,” outlined Dr Deepak Bhatt (Icahn School of Medicine at Mount Sinai, NY, USA) [1]. “However, bleeding associated with urgent surgery and spontaneous major bleeding are concerns with antiplatelet agents.” Therefore, a rapid-acting reversal agent is needed.

The phase 3 REVERSE-IT trial (NCT04286438) included 226 participants on ticagrelor who required urgent surgery or presented with major bleeding. These participants were exposed to bentracimab, a recombinant human IgG1 monoclonal antibody that binds to free ticagrelor. “Ticagrelor binds to the P2Y₁₂ receptor on platelets,” explained Dr Bhatt. “The idea is that the binding of bentracimab to free ticagrelor prevents binding of ticagrelor to the P2Y₁₂ receptor, allowing ADP to activate platelets.” The primary endpoint was the minimum percentage inhibition of P2Y₁₂ reaction unit (PRU) over 4 hours.

The percentage inhibition of PRU was significantly lower at 4 hours after bentracimab administration (P<0.001; see Figure). This finding was consistent across participants who needed surgery and participants who had spontaneous major bleeding. Moreover, adjudicated effective haemostasis was achieved in 94.3% of the participants. Dr Bhatt mentioned that there were 5 drug-related adverse events, but that none of these side effects were deemed serious or led to discontinuation of the study drug.

Figure: Percentage inhibition of P2Y₁₂ reaction unit (PRU) [1]




CI, confidence interval; PRU, P2Y12 reaction unit.

Bentracimab presented itself as a promising option for ticagrelor reversal, restoring platelet function and inducing haemostasis without considerable side effects. “The FDA granted orphan drug designation last week,” Dr Bhatt concluded.

1. Bhatt DL, et al. The main results of REVERSE-IT. Late-breaking Clinical Trials II, ACC 2025 Scientific Session, 29–31 March, Chicago, USA.

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Posted on 22 May 202522 May 2025