Reversal of antiplatelet effects of P2Y12i by monoclonal antibody fragment

REVERSE-IT: Effect of Bentracimab on Platelet Inhibition and Hemostasis in Patients on Ticagrelor with Major Bleeding or Requiring Urgent Procedures

News - Nov. 22, 2021

Presented at the American Heart Association’s Scientific Sessions 2021 by: Deepak Bhatt, MD - Brigham and Women’s Hospital, Boston, MA, USA.

Introduction and methods


The P2Y12 inhibitor ticagrelor has demonstrated to be effective in a broad range of patients, based on results of the PLATO, PEGASUS, THEMIS, THEMIS-PCI and THALES trials. Similar as with other antiplatelet drugs, there are concerns about bleedings associated with urgent or emergent invasive procedures in patients using ticagrelor. Because platelet transfusion is not an option for reversal of the antiplatelet effects of ticagrelor, there is a need for a rapid-acting reversal agent.

Ticagrelor is a reversal antiplatelet agent. This property has allowed the development of bentracimab, a recombinant human monoclonal antibody fragment that binds to free ticagrelor with high affinity and specificity.

A phase I and phase 2a trial in which healthy volunteers were randomized to bentracimab or placebo showed that bentracimab resulted in immediate and sustained reversal of ticagrelor with a bolus and prolonged infusion.

Study design

REVERSE-IT is a multicenter, open-label, prospective single-arm study in at least 200 patients who present with uncontrolled major of life-threating bleeding or who require urgent surgery or invasive procedures. Enrollment is ongoing and patients with use of ticagrelor within the prior 3 days who require ticagrelor reversal are eligible. The results reported were from a prespecified, interim analysis. There were 122 surgical patients and 7 bleeding patients for reversal analysis, and 113 surgical patients and 9 bleeding patients for effective hemostasis analysis.

Primary outcome

The primary reversal endpoint was the minimum percentage inhibition of platelet reactivity unit (PRU) within 4 hours of bentracimab initiation as assessed by Verity Now PRUTest platelet function assay.

Primary hemostasis endpoint was achievement of effective hemostasis within 24 hours after bentracimab using standardized definitions for uncontrolled major bleeding or urgent surgery of invasive procedure.

Main results

  • There was significant reversal with bentracimab of the effect of ticagrelor measured by % inhibition of PRU at 4 hours. At all the time point measured during the first 24 hours, there is a highly significant degree of reversal as assessed by the PRUTest.
  • When using the VASP test to assess platelet reactivity index (PRI), a similar results for reversal by bentracimab was observed.
  • The benefit by bentracimab was similar in surgical and bleeding patients.
  • Adjudicated achieved hemostasis was observed in 100% of surgical patients and in 77.8% of bleeding patients.
  • There was no evidence of platelet rebound activity.
  • None of the thrombotic events in the study population was related to bentracimab.


Bentracimab resulted in immediate and sustained reversal of the antiplatelet effects of ticagrelor in ticagrelor-treated patients undergoing invasive procedures or with major bleeding, demonstrated in an interim analysis of REVERSE-IT. There were high rates of good or excellent effective hemostasis. And benefits were consisted in prespecified subgroups.


The discussant G. Montalescot, MD (Paris, France) raised some questions on REVERSE-IT. There was a small number of patients with uncontrolled or life-threatening bleeding. Can you draw the same conclusions in this subgroup? Then, he asked ‘What was unethical in having a control group? And he noted there were 4 events immediately after reversal without an alternate explanation.

Then he raised some general questions. How do we get more clinical evidence for the bleedings, wait for post-market surveillance studies? Furthermore he wondered, how many cardiac surgery patients cannot wait 3 days for CABG? And after stenting before a procedure or operation, how much better is a reversal strategy than a cangrelor switching strategy?

- Our reporting is based on the information provided at the American Heart Association’s Scientific Sessions 2021 -

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