title: A pharmacodynamic comparison of a personalized strategy for anti-platelet therapy versus ticagrelor in achieving a therapeutic window.
abstract: BACKGROUND
  A therapeutic window in antiplatelet treatment has been associated with concurrent lowering of bleeding and ischemic risks. Prasugrel and ticagrelor provide potent platelet inhibition, but may increase bleeding. No study has evaluated a personalized therapy with selective use of novel P2Y12 inhibitory agents compared to empiric ticagrelor use. The objective of this study was to compare a personalized anti-platelet therapy strategy to empiric ticagrelor in achieving a therapeutic window.
  
  
  METHODS
  Using the CAPITAL registry, we performed a retrospective analysis to evaluate a personalized anti-platelet therapy (PAT) strategy, using a pharmacogenetic approach, and compared it to empiric ticagrelor. In the PAT group, carriers of CYP2C19*2 received prasugrel and non-carriers received clopidogrel. The primary outcome was the proportion of patients within a validated therapeutic window, after a steady state treatment (≥48h) of antiplatelet therapy, as measured by a P2Y12 reaction unit (PRU) >85 and <208.
  
  
  RESULTS
  Of 199 patients with platelet function measurements, 150 received PAT, while 49 received ticagrelor. Significantly more patients on PAT achieved the primary outcome (50.0% vs. 4.1%, p<0.0001). This was predominantly driven by an increase in low on-treatment reactivity with ticagrelor (95.9% vs. 37.3%, p<0.0001). Multivariable analysis demonstrated PAT to be the strongest predictor of achieving PRU values within the therapeutic window (odds ratio 20.27; 95% CI: 4.33-94.82, p=0.0001).
  
  
  CONCLUSIONS
  Patients treated with PAT were more likely to achieve a therapeutic window compared to a strategy of ticagrelor. Future prospective evaluation of novel PAT strategies will be required to prove clinical utility.
authors.affiliation: Division of Cardiology, University of Ottawa Heart Institute, Ottawa, ON, Canada.
authors.forename: Nikita
authors.initials: N
authors.lastname: Malhotra
authors.affiliation: Division of Cardiology, University of Ottawa Heart Institute, Ottawa, ON, Canada.
authors.forename: Joseph
authors.initials: J
authors.lastname: Abunassar
authors.affiliation: Cardiovascular Methods Centre, University of Ottawa Heart Institute, Ottawa, Ontario, Canada.
authors.forename: George A
authors.initials: GA
authors.lastname: Wells
authors.affiliation: Canadian Cardiovascular Genetics Centre, University of Ottawa Heart Institute, Ottawa, Ontario, Canada.
authors.forename: Ruth
authors.initials: R
authors.lastname: McPherson
authors.affiliation: Division of Cardiology, University of Ottawa Heart Institute, Ottawa, ON, Canada.
authors.forename: Angel
authors.initials: A
authors.lastname: Fu
authors.affiliation: Division of Cardiology, University of Ottawa Heart Institute, Ottawa, ON, Canada.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Hibbert
authors.affiliation: Division of Cardiology, University of Ottawa Heart Institute, Ottawa, ON, Canada.
authors.forename: Marino
authors.initials: M
authors.lastname: Labinaz
authors.affiliation: Division of Cardiology, University of Ottawa Heart Institute, Ottawa, ON, Canada.
authors.forename: Michel
authors.initials: M
authors.lastname: Le May
authors.affiliation: Division of Cardiology, University of Ottawa Heart Institute, Ottawa, ON, Canada.
authors.forename: Alexander
authors.initials: A
authors.lastname: Dick
authors.affiliation: Division of Cardiology, University of Ottawa Heart Institute, Ottawa, ON, Canada.
authors.forename: Chris
authors.initials: C
authors.lastname: Glover
authors.affiliation: Division of Cardiology, University of Ottawa Heart Institute, Ottawa, ON, Canada.
authors.forename: Michael
authors.initials: M
authors.lastname: Froeschl
authors.affiliation: Division of Cardiology, University of Ottawa Heart Institute, Ottawa, ON, Canada.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Marquis
authors.affiliation: Division of Cardiology, University of Ottawa Heart Institute, Ottawa, ON, Canada.
authors.forename: Luan
authors.initials: L
authors.lastname: Tran
authors.affiliation: Division of Cardiology, University of Ottawa Heart Institute, Ottawa, ON, Canada.
authors.forename: Jordan
authors.initials: J
authors.lastname: Bernick
authors.affiliation: Division of Cardiology, University of Ottawa Heart Institute, Ottawa, ON, Canada.
authors.forename: Aun-Yeong
authors.initials: AY
authors.lastname: Chong
authors.affiliation: Division of Cardiology, University of Ottawa Heart Institute, Ottawa, ON, Canada. Electronic address: dso@ottawaheart.ca.
authors.forename: Derek Y F
authors.initials: DY
authors.lastname: So
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D001778:Blood Coagulation Disorders / Q000188:drug therapy / Q000235:genetics; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010597:Pharmacogenetics / Q000379:methods* / Q000592:standards; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D010979:Platelet Function Tests / Q000379:methods; D057285:Precision Medicine / Q000379:methods* / Q000592:standards; D058921:Purinergic P2Y Receptor Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D012042:Registries; D012189:Retrospective Studies; D000077486:Ticagrelor; D016896:Treatment Outcome
chemical_list: D010975:Platelet Aggregation Inhibitors; D058921:Purinergic P2Y Receptor Antagonists; D000077486:Ticagrelor; D000241:Adenosine
keywords: Personalized anti-platelet therapy; Therapeutic window; Ticagrelor