December 22, 2021NEJM Evidence58 citationsOpen Access
View Full PaperBentracimab for Ticagrelor Reversal in Patients Undergoing Urgent Surgery
Key Result
Bentracimab provided rapid and sustained reversal of ticagrelor, achieving adjudicated hemostasis in more than 90% of patients (P<0.001).
Structured PICO
Does bentracimab reverse the antiplatelet effects of ticagrelor and achieve clinical hemostasis in ticagrelor-treated patients requiring urgent surgery or with major hemorrhage?
P
Population
150 ticagrelor-treated patients requiring urgent surgery or experiencing major hemorrhage, evaluated in a single-arm prospective study.
I
Intervention
Bentracimab (intravenous monoclonal antibody)
O
Outcome
Extent of reversal determined using the VerifyNow P2Y12 assay and clinical hemostasis assessed by central adjudicationsurrogate
Bentracimab provides immediate and sustained reversal of ticagrelor's antiplatelet effects, achieving effective clinical hemostasis in patients requiring urgent surgery.
Main Result
p-value: p=<0.001
Abstract
BACKGROUND: Ticagrelor is a reversible oral P2Y12 platelet inhibitor used to treat patients with acute coronary syndromes, prior myocardial infarction, high-risk coronary artery disease, transient ischemic attack, or ischemic stroke. A healthy volunteer study showed that the intravenous monoclonal antibody bentracimab rapidly reverses ticagrelor, but the effect in patients was unknown. METHODS: In a prespecified interim analysis of a single-arm, prospective study, bentracimab was evaluated in ticagrelor-treated patients who required urgent surgery or had major hemorrhage. The extent of reversal was determined using the VerifyNow P2Y12 assay. Clinical hemostasis was assessed by central adjudication using validated criteria. Treatment-emergent safety events were evaluated. The trial is ongoing and will enroll approximately 200 patients with evaluable data. RESULTS: Of 150 enrolled patients, 142 required urgent surgery and 8 had major hemorrhage. For the end-point analysis, 129 patients had analyzable platelet data; 122 had data on adjudicated hemostasis. Bentracimab provided a rapid reversal of ticagrelor’s antiplatelet effects within 5 to 10 minutes. The reversal was sustained for more than 24 hours, as measured with the VerifyNow P2Y12 and vasodilator-stimulated phosphoprotein phosphorylation assays (P<0.001, with both assays and in all subgroups). Adjudicated hemostasis was achieved for more than 90% of patients (P<0.001); approximately 5% of patients had thrombotic events. No allergic or infusion-related reactions were reported. CONCLUSIONS: Bentracimab provided immediate and sustained reversal of the antiplatelet effects of ticagrelor in patients undergoing surgical procedures. (Funded by PhaseBio Pharmaceuticals, Inc.; ClinicalTrials.gov number, NCT04286438.)