title: Impact of cangrelor overdosing on bleeding complications in patients undergoing percutaneous coronary intervention: insights from the CHAMPION trials.
abstract: Overdosing of parenteral antithrombotic therapies can increase the risk of bleeding. Cangrelor is a potent intravenous platelet P2Y12 receptor antagonist with rapid onset and offset of action. In patients undergoing percutaneous coronary interventions (PCI), compared with control, cangrelor (30 µg/kg bolus, followed immediately by a 4 µg/kg per minute infusion for 2-4 h or until the conclusion of the index PCI, whichever was longer) reduces periprocedural thrombotic complications without an increase in major bleeding complications, although minor bleeding is increased. The impact of cangrelor overdosing on bleeding is unknown and represented the aim of this analysis. Patients with cangrelor overdosing were identified among safety population patients enrolled in the CHAMPION program (n = 25,107). Overdose was defined as administration of an excess >20 % of the bolus dose (30 μg/kg) and/or infusion rate (4 μg/kg per min). Bleeding complications were assessed. Among the safety analysis population in the CHAMPION program, 12,565 patients received cangrelor. A total of 36 overdosed cangrelor patients (0.29 %) were identified in this pooled analysis (20 with both bolus and infusion, 5 with bolus only, and 11 with infusion only). In the majority of patients, the dose did not exceed 2.5 times the recommended dose. Bleeding events were balanced between treatment arms and were consistent with those in the overall CHAMPION program. Only one overdosed patient experienced a serious bleed. There was no correlation between bleeding and magnitude of cangrelor overdose. In a large clinical trial program of patients undergoing PCI, cangrelor overdosing was rare and not associated with an increase in bleeding complications, an observation that may be attributed to its very short-half life and rapid offset of action.
authors.affiliation: University of Florida College of Medicine-Jacksonville, 655 West 8th Street, Jacksonville, FL, 32209, USA, dominick.angiolillo@jax.ufl.edu.
authors.forename: Dominick J
authors.initials: DJ
authors.lastname: Angiolillo
authors.forename: Deepak L
authors.initials: DL
authors.lastname: Bhatt
authors.forename: Ph Gabriel
authors.initials: PG
authors.lastname: Steg
authors.forename: Gregg W
authors.initials: GW
authors.lastname: Stone
authors.forename: Harvey D
authors.initials: HD
authors.lastname: White
authors.forename: C Michael
authors.initials: CM
authors.lastname: Gibson
authors.forename: Christian W
authors.initials: CW
authors.lastname: Hamm
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Price
authors.forename: Jayne
authors.initials: J
authors.lastname: Prats
authors.forename: Tiepu
authors.initials: T
authors.lastname: Liu
authors.forename: Kenneth W
authors.initials: KW
authors.lastname: Mahaffey
authors.forename: Robert A
authors.initials: RA
authors.lastname: Harrington
mesh_terms: D000249:Adenosine Monophosphate / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D062787:Drug Overdose / Q000097:blood / Q000453:epidemiology; D005260:Female; D006470:Hemorrhage / Q000097:blood / Q000139:chemically induced / Q000453:epidemiology; D006801:Humans; D008297:Male; D062645:Percutaneous Coronary Intervention
chemical_list: D000249:Adenosine Monophosphate; C117446:cangrelor