Ticagrelor Antidote Bentracimab Safely Reverses Antiplatelet Effects in Phase 3 REVERSE-IT Trial

Bentracimab, an investigational antidote to the antiplatelet drug ticagrelor, safely and effectively reversed its antiplatelet effects in patients undergoing urgent surgery or experiencing major bleeding, according to updated findings from the phase 3 REVERSE-IT trial.¹

Deepak L. Bhatt, MD, MPH, MBA | Image credit: ACC

Presented at the American College of Cardiology 2025 Annual Scientific Session (ACC.25), the late-breaking findings showed that 94.3% of patients achieved normal blood clotting and vessel repair after bentracimab infusion. This included 100% of those needing surgery and 83.1% of those with major bleeding. The antidote restored platelet function in minutes and was not linked to serious allergic reactions or discontinuations due to side effects.

“Based on REVERSE-IT, bentracimab appears to be a very promising option for ticagrelor reversal,” Deepak L. Bhatt, MD, MPH, MBA, director of Mount Sinai Fuster Heart Hospital and principal investigator of the study, said during an ACC.25 press conference. “Of course, there's an ongoing regulatory assessment of bentracimab. We'll have to see how that goes, though just last week, the FDA did grant bentracimab orphan drug designation.”

Ticagrelor is commonly prescribed alongside aspirin for dual antiplatelet therapy to prevent recurrent cardiovascular events after stent placement.² However, like other blood thinners, its antiplatelet action significantly raises the risk of dangerous bleeding in emergency situations. Existing methods like platelet transfusions are ineffective in patients treated with ticagrelor because of the drug’s unique mechanism. That gap in care prompted development of bentracimab, a monoclonal antibody specifically designed to neutralize ticagrelor’s effects.

“A patient on ticagrelor who needs emergency heart surgery is at high risk for developing serious bleeding during the surgery,” Bhatt explained. “If you delay the surgery, there’s a risk the patient could have a heart attack.”

REVERSE-IT enrolled 226 patients across the US, Canada, Europe, and China from 2020 to 2024.¹ All participants had received ticagrelor within 3 days of enrollment and either needed urgent surgery or were experiencing major bleeding. The primary end point was the extent of platelet function restoration within 4 hours of starting a bentracimab infusion, with secondary endpoints including clinical hemostasis and safety outcomes.

Platelet function began returning to normal within 5 to 10 minutes of infusion in over 80% of patients, and more than 91% reached normal function within 30 minutes. The VerifyNow P2Y12 assay confirmed these effects with statistical significance (P < .0001) across both surgical and bleeding subgroups.

Patients in both subgroups also saw high rates of hemostasis, with effective hemostasis achieved by 95% of total eligible patients, including 100% of those undergoing surgery and 79.5% of those with major bleeding. Serious adverse events (SAEs) occurred in 61 patients, including 7 thrombotic SAEs. No reactions were attributed to bentracimab, and there were no allergic SAEs or treatment discontinuations due to the study drug.

According to experts, bentracimab could address a key clinical dilemma among providers: the hesitancy to prescribe ticagrelor despite its benefits due to the fear of uncontrollable bleeding. With a reversal agent now demonstrating both safety and efficacy, if approved, clinicians could become more confident in using potent antiplatelet therapy where appropriate.

“The ability to reverse the antiplatelet effect in a clinical situation where you deem that's going to help improve the patient's clinical outcome—either major bleeding or in an urgent surgery—is going to be a really welcome addition to our ability to manage these particular patients,” Toby C. Trujillo, PharmD, professor of clinical pharmacy at the University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, member of the ACC cardiovascular team pharmacist workgroup, said during a press conference discussion of the study.

Limitations of the study include a relatively small number of Black patients (n = 5) and the absence of a control group. However, given the life-threatening scenarios involved and positive data from the randomized phase 1 trial data compared with placebo, investigators deemed it unethical to include a placebo arm in the phase 3 study.

Importantly, the study was funded by bentracimab developers PhaseBio Pharmaceuticals and SFJ Pharma, the latter of which Bhatt is a paid consultant to. These findings are anticipated to support the drug’s FDA approval in this indication.

References

1. Bhatt DL, Pollack CV, Mazer CD, et al. Bentracimab for ticagrelor reversal in patients undergoing urgent surgery: the main results of the phase 3 REVERSE-IT trial. Abstract presented at: ACC.25; March 29, 2025; Chicago, IL.
2. Ticagrelor antidote safely, effectively restores platelet function and treats bleeding. News release. American College of Cardiology. March 29, 2025. Accessed March 29, 2025. https://www.acc.org/About-ACC/Press-Releases/2025/03/29/15/23/Ticagrelor-Antidote-Safely