New drug reverses antiplatelet effects of ticagrelor, helping surgeons avoid a 'bloody mess'
As ticagrelor goes generic in the coming years, there is an expectation that it will see much wider adoption and replace generic clopidogrel during the treatment of many cardiac patients. So there was a lot of interest in the Phase 3 REVERSE-IT trial for the investigational ticagrelor-reversal drug bentracimab when it was presented as a late-breaker at ACC.25, the annual meeting of the American College of Cardiology.
The compelling data for the investigational monoclonal antibody offers hope for clinicians managing patients on ticagrelor who face life-threatening bleeding events or require urgent surgery, with the ability to stop the antiplatelet effect very quickly.
"It would be useful to be able to reverse ticagrelor in someone that has a stent that's on aspirin and ticagrelor, but has an aortic dissection. What are you going to do? You can't wait a week to operate. You have to operate right now. And if they're on ticagrelor and you could reverse, it could be lifesaving," explained trial principal investigator Deepak L. Bhatt, MD, MPH, MBA, director of Mount Sinai Fuster Heart Hospital and the Dr. Valentin Fuster Professor of Cardiovascular Medicine at the Icahn School of Medicine at Mount Sinai. He spoke to Cardiovascular Business in the above video interview.
He added that patients with an intracranial hemorrhage where doctors could reverse the ticagrelor effect would also be very helpful. There also might be advantages for patients who need elective surgery.
If bentracimab gains regulatory approval, Bhatt said it could be a game-changer—not just for emergency management, but potentially for elective surgical planning and broader antiplatelet strategies.
Key REVERSE-IT trial findings
Bentracimab is a recombinant human monoclonal antibody (IgG1) that binds to ticagrelor and its active metabolite, neutralizing their antiplatelet effects. While ticagrelor is a potent, reversible P2Y12 inhibitor with broad indications from acute coronary syndromes (ACS) to stroke prevention, it poses challenges when urgent procedures or major bleeding arise.
“In our Phase 1 study, we showed it quickly, and really completely, reversed ticagrelor's effect within five minutes," Bhatt explained.
The Phase 3 REVERSE-IT trial was a global, single-arm, non-randomized trial. It was structured this way due to ethical concerns over withholding a potentially lifesaving reversal agent. It enrolled patients on ticagrelor facing critical bleeding or requiring urgent or emergent procedures. There were 212 patients who met eligibility criteria and had an independent assessment of the degree of bleeding control. They included 141 surgery and 71 bleeding patients.
Among surgical patients, 100% achieved effective hemostasis according to adjudication by an independent Clinical Events Committee (CEC). In patients with major bleeding, 83% achieved effective hemostasis, including a subset of approximately 20 patients with intracranial hemorrhage, where 80% had favorable outcomes.
“Surgeons I talked to in the trial said when they operate on ticagrelor in real life, it's a bloody mess. In this trial, when they operated after bentracimab, it was a clean surgical field. So these were pretty dramatic differences in their words," Bhatt related.
Bentracimab could become a must-have drug in the future
Bentracimab is still investigational and not yet cleared by the U.S. Food and Drug Administration (FDA). The FDA recently granted it an orphan drug designation, signaling regulatory momentum. Bhatt emphasized its potential to become a critical asset in emergency settings.
"I think it's the sort of drug that every emergency room and ICU would have to stock. A cardiac care unit would have to stock a couple of doses, as would every cath lab," he said.
With ticagrelor set to go generic worldwide in the near future, and with its expanding list of approved uses, bentracimab could make ticagrelor even more attractive to prescribers, Bhatt said.
Rethinking the cardiology antiplatelet strategy?
The trial’s implications may go further, potentially reshaping how antiplatelet agents are chosen. Bentracimab is specific to ticagrelor; it does not reverse other P2Y12 inhibitors like clopidogrel or prasugrel, which bind irreversibly to platelets and are not affected by the monoclonal antibodies. But this specificity raises an intriguing possibility of changing to ticagrelor because it would enable increased safety if patients experience trauma, intracranial hemorrhage or require surgery.
“It’s a clever idea,” Bhatt acknowledged. “We haven’t studied that yet, and there are risks with switching agents, but it might be worth exploring. Especially if elective or semi-elective surgeries could be accelerated safely.”
Dave Fornell has covered healthcare for more than 17 years, with a focus in cardiology and radiology. Fornell is a 5-time winner of a Jesse H. Neal Award, the most prestigious editorial honors in the field of specialized journalism. The wins included best technical content, best use of social media and best COVID-19 coverage. Fornell was also a three-time Neal finalist for best range of work by a single author. He produces more than 100 editorial videos each year, most of them interviews with key opinion leaders in medicine. He also writes technical articles, covers key trends, conducts video hospital site visits, and is very involved with social media. E-mail: [email protected]