ACC 2025: Ticagrelor Antidote Restores Platelet Function, Treats Bleeding

New data presented at the American College of Cardiology 2025 Scientific Session demonstrate that a drug developed as an antidote to the antiplatelet agent ticagrelor (Brilinta; AstraZeneca) safely and effectively reversed ticagrelor’s antiplatelet effects in patients undergoing urgent surgery or experiencing major bleeding.¹

Ticagrelor increases patients’ risk of experiencing a bleeding episode | Image credit: alfa27 | stock.adobe.com

The availability of this option could make physicians more comfortable when prescribing ticagrelor, which, in turn,could help solve the challenge of undertreatment with antiplatelet therapy, explained presented Deepak L. Bhatt, MD, MPH, MBA, director of the Mount Sinai Fuster Heart Hospital and the study’s principal investigator, in a news release.²

Ticagrelor is used in combination with aspirin to prevent repeat heart attacks and blood clots in individuals who have had a stent placed in a coronary artery. As a dual antiplatelet therapy, it works by blocking a protein that stimulates platelets to form a clot in response to bleeding. However, ticagrelor increases patients’ risk of experiencing a bleeding episode, especially during urgent surgery or another type of invasive procedure.^1,2

Bentracimab is a monoclonal antibody fragment developed as a reversal agent for ticagrelor. In a prespecified interim analysis published in 2022, investigators found that it provided immediate and sustained reversal of the antiplatelet effects of ticagrelor in patients undergoing surgical procedures. In the study, of 150 enrolled patients, 142 required urgent surgery and 8 had major hemorrhage. Bentracimab provided rapid reversal of ticagrelor’s effects within 5 to 10 minutes, with reversal sustained for more than 24 hours. Adjudicated hemostasis was achieved for more than 90% of patients and approximately 5% of patients had thrombotic events.³

“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. Or say a patient on ticagrelor develops bleeding in the brain. Ordinarily, we might give platelet transfusions to control the bleeding, but because of ticagrelor’s mechanism of action, platelet transfusions don’t work in patients who are taking it. Bentracimab was developed as an antidote to ticagrelor precisely for use in situations like this.”²

In the single-arm, phase 3 REVERSE-IT study, 226 patients were enrolled between 2020 and 2024 in the US, Canada, Europe, and China. Eligible participants must have received ticagrelor within the previous 3 days and either needed surgery or another invasive procedure that could not be delayed (the surgery group) or were experiencing major bleeding (the bleeding group).^1,2

Participants had an average age of 65 years, 79.2% were men, and 76.1% were White. Most (75.7%) had hypertension, 74.3% had experienced a prior heart attack, 41.6% had diabetes, and most were overweight (average body mass index 28.6). Most patients in the surgery group (78.7%) were undergoing cardiac bypass surgery and all patients received bentracimab by slow infusion over about 16 hours.^1,2

The primary end point was the degree of restoration of normal platelet function after the start of bentracimab infusion compared with baseline. It was statistically significant and results were similar for both the surgery and bleeding groups, as well as in all prespecified subgroups of patients, including age and sex.^1,2

In total, 94.3% of patients—100% in the surgical group and 83.1% in the bleeding group—achieved normal blood clotting and repair of damaged blood vessels after bentracimab treatment. Again, results were similar in both groups and subgroups.^1,2

Approximately 18% of patients in the surgery group experienced serious adverse events deemed related to treatment, compared with approximately 12% in the bleeding group. No participants had serious allergic reactions to bentracimab treatment, and no patients withdrew from the trial because of treatment-related adverse drug reactions.^1,2

“The antidote, bentracimab, rapidly restored normal platelet function in ticagrelor-treated patients,” Bhatt said. “This was true for both surgical patients and those with major bleeding. Most patients in both groups also achieved normal hemostasis—that is, normal blood clotting and repair of damaged blood vessels—after bentracimab treatment.”²

The study authors noted that there was a limited number of Black participants, and the trial had no control group because the investigators believed it would be unethical to randomly assign some patients to receive a placebo when they were experiencing or were at high risk for potentially life-threatening bleeding. In the randomized phase 1 trial, healthy volunteers who received bentracimab rapidly recovered normal platelet function compared with those who received the placebo.²

REFERENCES

1. Bhatt DL. Ticagrelor antidote safely, effectively restores platelet function and treats bleeding. Presented at: American College of Cardiology 2025 Scientific Session. March 29, 2025.

2. Ticagrelor Antidote Safely, Effectively Restores Platelet Function and Treats Bleeding. News release. American College of Cardiology. March 29, 2025. Accessed March 29, 2025.

3. Bhatt DL, Pollach Jr CV, Mazer CD, et al. Bentracimab for ticagrelor reversal in patients undergoing urgent surgery. NEJM Evid. 2022;1(3). doi:10.1056/EVIDoa2100047