title: Refuting the ticagrelor-aspirin black box warning: and proposing a ticagrelor early-PCI black box warning.
abstract: BACKGROUND
  Ticagrelor, a novel reversible antiplatelet agent, has a black box warning to avoid maintenance doses of aspirin>100mg. However, a significant ticagrelor-early percutaneous coronary intervention (PCI) interaction exists.
  
  
  OBJECTIVE
  To discuss the inappropriateness of the black box warning for aspirin doses>100mg with ticagrelor and the appropriateness (and need) for a black box warning for ticagrelor patients needing early (within 24 hours of randomization) PCI.
  
  
  RESULTS
  The FDA Complete Response Review for ticagrelor indicates that aspirin doses ≥ 300 mg/daily was not a significant interaction. In the ticagrelor-aspirin ≥ 300 mg cohort, all-cause mortality (through study end) and cardiovascular (CV) mortality (through study end) were not significantly increased (HR=1.27; 95% CI, 0.84-1.93, p=0.262 and HR=1.39; 95% CI:0.87-2.2, p=0.170), respectively. However, in patients treated with early (within 24 hours) PCI, ticagrelor significantly increased all-cause mortality (30 day: HR=1.89; 95% CI: 1.26-2.81, p=0.002, and through study end, HR=1.41; 95% CI,1.08-1.84, p=0.012) and increased CV mortality (30 day: HR=1.31; 95% CI: 0.97-1.77, p=0.075, and through study end, HR=1.35; 95% CI, 0.995-1.82, p=0.054) compared to clopidogrel.
  
  
  CONCLUSIONS
  Early-PCI was more prevalent in the US versus outside-US regions (61% versus 49%). The black box warning for the use of maintenance aspirin doses over 100mg/daily with ticagrelor is inappropriate and ignores the more important, credible, and highly significant ticagrelor-early PCI adverse interaction in PLATO.
authors.affiliation: Wegmans Pharmacy, 500 South Meadow Street, Ithaca NY 14850, United States. Electronic address: jjdinicol@gmail.com.
authors.forename: James J
authors.initials: JJ
authors.lastname: DiNicolantonio
authors.forename: Victor L
authors.initials: VL
authors.lastname: Serebruany
authors.forename: Ales
authors.initials: A
authors.lastname: Tomek
mesh_terms: D054058:Acute Coronary Syndrome / Q000628:therapy*; D000241:Adenosine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D001241:Aspirin / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D006801:Humans; D062645:Percutaneous Coronary Intervention; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use; D058921:Purinergic P2Y Receptor Antagonists / Q000627:therapeutic use; D000077486:Ticagrelor; D013997:Time Factors
chemical_list: D010975:Platelet Aggregation Inhibitors; D058921:Purinergic P2Y Receptor Antagonists; D000077486:Ticagrelor; D000241:Adenosine; D001241:Aspirin
keywords: Clinical Trials; Clopidogrel; Percutaneous Coronary Interventions; Ticagrelor