New Research Finds PB2452 May Reverse Antiplatelet Effects of Ticagrelor

The administration of intravenous PB2452 may provide immediate and sustained reversal of the antiplatelet effects of ticagrelor, according to research published March 17 in the New England Journal of Medicine and presented during ACC.19 in New Orleans, LA.

Deepak L. Bhatt, MD, MPH, FACC, et al., evaluated intravenous PB2452 as a ticagrelor reversal agent and assessed platelet function in 64 healthy volunteers before and after 48 hours of ticagrelor pretreatment, and again after the administration of PB2452 or placebo. Platelet function was assessed with the use of light transmission aggregometry – a point-of-care P2Y12 platelet-reactivity test – and a vasodilator-stimulated phosphoprotein assay.

Of the 64 volunteers who underwent randomization, 48 were assigned to receive PB2452 and 16 were assigned to receive placebo. Results showed that after 48 hours of ticagrelor pretreatment, platelet aggregation was suppressed by approximately 80 percent.

As measured by multiple assays, PB2452 administered as an initial intravenous bolus followed by a prolonged infusion (8, 12 or 16 hours) was found to be associated with a significantly greater increase in platelet function than placebo. Furthermore, ticagrelor reversal occurred within five minutes after the initiation of PB2452 and was sustained for more than 20 hours.

The researchers note there was no evidence of a rebound in platelet activity after drug cessation, and adverse events related to the trial drug were limited mainly to issues involving the infusion site.

"Antiplatelet therapy is an essential part of secondary prevention of cardiovascular events," the researchers explain. "The ability to reverse the action of novel oral anticoagulants has been a major advance in antithrombotic therapy."

Keywords: ACC19, ACC Annual Scientific Session, Adenosine, Purinergic P2Y Receptor Antagonists, Angina, Stable, Acute Coronary Syndrome

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