title: Pharmacodynamic Effects of Ticagrelor Dosing Regimens in Patients on Maintenance Ticagrelor Therapy: Results From a Prospective, Randomized, Double-Blind Investigation.
abstract: OBJECTIVE
  The aim of this study was to assess the impact of ticagrelor dosing regimens on pharmacodynamic (PD) profiles in patients on maintenance ticagrelor therapy.
  
  
  BACKGROUND
  Many patients on maintenance P2Y12-inhibiting therapies may require coronary revascularization procedures, raising a common clinical question with regard to the dosing regimen of the P2Y12-inhibiting agent to be used. To date, investigations assessing dosing regimens of P2Y12 receptor inhibitors in patients on maintenance therapy have been only assessed with thienopyridines, but not with ticagrelor.
  
  
  METHODS
  This was a prospective, randomized, double-blind, placebo-controlled study assessing the PD effects of 2 dosing regimens of ticagrelor in patients on standard aspirin and ticagrelor maintenance therapy. A total of 60 patients were randomized to either 90 mg (maintenance dose [MD] group) or 180 mg (loading dose [LD] group) dose of ticagrelor. PD assessments were conducted at 3 time points (baseline, 1 h and 4 h). PD assessments were defined according to the platelet reactivity index (PRI) (vasodilator-stimulated phosphoprotein phosphorylation assay), P2Y12 reaction unit (VerifyNow P2Y12 assay) and adenosine diphosphate-induced platelet aggregation by light transmittance aggregometry.
  
  
  RESULTS
  There were no differences in baseline levels of platelet reactivity with all assays. Intergroup comparisons by means of repeated-measures analysis adjusted for baseline PRI values showed that the LD group had significantly lower PRI levels compared with the MD group during the overall study time course (p = 0.031). Consistent findings were found for P2Y12 reaction unit (p = 0.026) and light transmittance aggregometry (p = 0.004). Intragroup comparisons showed that a more prompt and sustained platelet inhibitory effect was achieved more consistently with an LD regimen compared with a MD regimen.
  
  
  CONCLUSIONS
  In patients on maintenance ticagrelor therapy, a 180-mg LD regimen of ticagrelor is associated with more potent and prompt platelet inhibition compared with a 90-mg MD. (Impact of Ticagrelor Re-Load Pharmacodynamic Profiles; NCT01731041).
authors.affiliation: University of Florida College of Medicine-Jacksonville, Jacksonville, Florida.
authors.forename: Jung Rae
authors.initials: JR
authors.lastname: Cho
authors.affiliation: University of Florida College of Medicine-Jacksonville, Jacksonville, Florida.
authors.forename: Fabiana
authors.initials: F
authors.lastname: Rollini
authors.affiliation: University of Florida College of Medicine-Jacksonville, Jacksonville, Florida.
authors.forename: Francesco
authors.initials: F
authors.lastname: Franchi
authors.affiliation: University of Florida College of Medicine-Jacksonville, Jacksonville, Florida.
authors.forename: Christopher
authors.initials: C
authors.lastname: DeGroat
authors.affiliation: University of Florida College of Medicine-Jacksonville, Jacksonville, Florida.
authors.forename: Mona
authors.initials: M
authors.lastname: Bhatti
authors.affiliation: University of Florida College of Medicine-Jacksonville, Jacksonville, Florida.
authors.forename: Elizabeth C
authors.initials: EC
authors.lastname: Dunn
authors.affiliation: University of Florida College of Medicine-Jacksonville, Jacksonville, Florida.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Ferrante
authors.affiliation: University of Florida College of Medicine-Jacksonville, Jacksonville, Florida.
authors.forename: Ana
authors.initials: A
authors.lastname: Muniz-Lozano
authors.affiliation: University of Florida College of Medicine-Jacksonville, Jacksonville, Florida.
authors.forename: Siva
authors.initials: S
authors.lastname: Suryadevara
authors.affiliation: University of Florida College of Medicine-Jacksonville, Jacksonville, Florida.
authors.forename: Martin M
authors.initials: MM
authors.lastname: Zenni
authors.affiliation: University of Florida College of Medicine-Jacksonville, Jacksonville, Florida.
authors.forename: Luis A
authors.initials: LA
authors.lastname: Guzman
authors.affiliation: University of Florida College of Medicine-Jacksonville, Jacksonville, Florida.
authors.forename: Theodore A
authors.initials: TA
authors.lastname: Bass
authors.affiliation: University of Florida College of Medicine-Jacksonville, Jacksonville, Florida. Electronic address: dominick.angiolillo@jax.ufl.edu.
authors.forename: Dominick J
authors.initials: DJ
authors.lastname: Angiolillo
mesh_terms: D054058:Acute Coronary Syndrome / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D000241:Adenosine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D000368:Aged; D015415:Biomarkers / Q000097:blood; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000097:blood; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D005431:Florida; D006801:Humans; D008297:Male; D008840:Microfilament Proteins / Q000097:blood; D008875:Middle Aged; D010750:Phosphoproteins / Q000097:blood; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D010979:Platelet Function Tests; D011446:Prospective Studies; D058921:Purinergic P2Y Receptor Antagonists / Q000008:administration & dosage* / Q000009:adverse effects; D058925:Receptors, Purinergic P2Y12 / Q000097:blood / Q000187:drug effects; D000077486:Ticagrelor; D013997:Time Factors; D016896:Treatment Outcome; D000098662:Vasodilator-Stimulated Phosphoprotein
chemical_list: D015415:Biomarkers; D015815:Cell Adhesion Molecules; D008840:Microfilament Proteins; C548576:P2RY12 protein, human; D010750:Phosphoproteins; D010975:Platelet Aggregation Inhibitors; D058921:Purinergic P2Y Receptor Antagonists; D058925:Receptors, Purinergic P2Y12; D000098662:Vasodilator-Stimulated Phosphoprotein; D000077486:Ticagrelor; D000241:Adenosine
keywords: coronary artery disease; platelet reactivity; ticagrelor