title: Pharmacodynamic evaluation of switching from ticagrelor to prasugrel in patients with stable coronary artery disease: Results of the SWAP-2 Study (Switching Anti Platelet-2).
abstract: OBJECTIVE
  The goal of this study was to evaluate the pharmacodynamic effects of switching patients from ticagrelor to prasugrel.
  
  
  BACKGROUND
  Clinicians may need to switch between more potent P2Y12 inhibitors because of adverse effects or switch to the use of a once-daily dosing regimen due to compliance issues.
  
  
  METHODS
  After a 3- to 5-day run-in phase with a ticagrelor 180-mg loading dose (LD) followed by a ticagrelor 90-mg twice-daily maintenance dose (MD), aspirin-treated patients (N = 110) with stable coronary artery disease were randomized to continue ticagrelor or switch to prasugrel 10-mg once-daily MD, with or without a 60-mg LD. Pharmacodynamic assessments were defined according to P2Y12 reaction unit (PRU) (P2Y12 assay) and platelet reactivity index (vasodilator-stimulated phosphoprotein phosphorylation assay) at baseline (before and after the run-in phase) and 2, 4, 24, and 48 h and 7 days after randomization.
  
  
  RESULTS
  Platelet reactivity was significantly greater at 24 and 48 h after switching to prasugrel versus continued therapy with ticagrelor, although to a lesser extent in those receiving an LD. Mean PRU remained significantly higher in the combined prasugrel groups versus the ticagrelor group (least-squares mean difference: 46 [95% confidence interval 25 to 67]) and did not meet the primary noninferiority endpoint (upper limit of the confidence interval ≤45), although PRU in the prasugrel cohort was lower at 7 days than at 24 or 48 h. Accordingly, rates of high on-treatment platelet reactivity were higher at 24 and 48 h in both prasugrel groups. At 7 days, there was no difference in high on-treatment platelet reactivity rate between the combined prasugrel and ticagrelor groups.
  
  
  CONCLUSIONS
  Compared with continued ticagrelor therapy, switching from ticagrelor to prasugrel therapy was associated with an increase in platelet reactivity that was partially mitigated by the administration of an LD.
authors: Division of Cardiology, University of Florida College of Medicine, Jacksonville, Florida. Electronic address: dominick.angiolillo@jax.ufl.edu.
authors: Dominick J
authors: DJ
authors: Angiolillo
authors: Southampton University Hospital, Southampton, United Kingdom.
authors: Nicholas
authors: N
authors: Curzen
authors: Sinai Center for Thrombosis Research, Sinai Hospital of Baltimore, Baltimore, Maryland.
authors: Paul
authors: P
authors: Gurbel
authors: Medical Affairs, Daiichi Sankyo, Inc., Parsippany, New Jersey.
authors: Paul
authors: P
authors: Vaitkus
authors: Medical Affairs, Daiichi Sankyo, Inc., Parsippany, New Jersey.
authors: Fred
authors: F
authors: Lipkin
authors: Medical Affairs, Daiichi Sankyo, Inc., Parsippany, New Jersey.
authors: Wei
authors: W
authors: Li
authors: Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana.
authors: Joseph A
authors: JA
authors: Jakubowski
authors: Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana.
authors: Marjorie
authors: M
authors: Zettler
authors: Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana.
authors: Mark B
authors: MB
authors: Effron
authors: Department of Clinical Pharmacology, Clinic for Cardiology and Angiology II, Universitäts-Herzzentrum Freiburg-Bad Krozingen, Bad Krozingen, Germany.
authors: Dietmar
authors: D
authors: Trenk
mesh_terms: D000241:Adenosine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D000293:Adolescent; D000328:Adult; D000368:Aged; D001792:Blood Platelets / Q000187:drug effects*; D003324:Coronary Artery Disease / Q000188:drug therapy* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000008:administration & dosage / Q000493:pharmacokinetics*; D010979:Platelet Function Tests; D000068799:Prasugrel Hydrochloride; D058921:Purinergic P2Y Receptor Antagonists / Q000008:administration & dosage / Q000493:pharmacokinetics; D013876:Thiophenes / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000077486:Ticagrelor; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D010879:Piperazines; D058921:Purinergic P2Y Receptor Antagonists; D013876:Thiophenes; D000068799:Prasugrel Hydrochloride; D000077486:Ticagrelor; D000241:Adenosine
keywords: drug interaction; pharmacodynamics; platelet function; prasugrel; ticagrelor