title: Pharmacodynamic Effects of Switching From Prasugrel to Ticagrelor: Results of the Prospective, Randomized SWAP-3 Study.
abstract: This study sought to assess the pharmacodynamic (PD) effects of switching to ticagrelor patients who were treated with prasugrel after undergoing percutaneous coronary intervention in the setting of an acute coronary syndrome.
  
  
  
  In clinical practice, there is a frequent need to switch between P2Y12 receptor inhibitors. However, concerns on drug interactions have emerged when switching therapies. To date, the PD effects of switching from prasugrel to ticagrelor have yet to be investigated.
  
  
  
  This was a prospective, randomized, open-label, 3-arm, parallel-design study conducted in patients (n = 82) on maintenance dual antiplatelet therapy with aspirin (81 mg QD) and prasugrel (10 mg QD). Patients were randomized to continue prasugrel 10 mg QD or switch to ticagrelor 90 mg bid, with or without a 180 mg loading dose (LD), for 1 week. PD assessments included P2Y12 reaction units (PRU) by VerifyNow, platelet reactivity index by vasodilator-stimulated phosphoprotein (VASP), and platelet aggregation by light transmittance aggregometry (LTA) at a total of 6 time points: baseline, 2 h, 4 h, 24 h, 48 h, and 1 week after randomization.
  
  
  
  After switching to ticagrelor, PRU levels decreased as early as 2 h after drug administration. Mean PRU levels remained low during the study time course, without evidence of drug interactions. The primary endpoint of noninferiority of ticagrelor (2 arms combined) versus prasugrel measured by PRU at 1 week was met (least squares mean difference: -18; 95% confidence interval: -41 to 5). There was no increase in rates of high on-treatment platelet reactivity (PRU >208), which were overall very low throughout the study time course. Similar levels of platelet reactivity were observed irrespective of the use of a ticagrelor LD. Parallel findings were observed with VASP and LTA.
  
  
  
  Switching from prasugrel to ticagrelor leads to transiently higher levels of platelet inhibition, irrespective of the use of a LD, without evidence of drug interactions. (Pharmacodynamic Evaluation of Switching From Prasugrel to Ticagrelor [SWAP3]; NCT02016170).
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: Gabriel Todd
authors.initials: GT
authors.lastname: Faz
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: Yongwhi
authors.initials: Y
authors.lastname: Park
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: Estela
authors.initials: E
authors.lastname: Thano
authors.affiliation: University of Florida College of Medicine-Jacksonville, Jacksonville, Florida.
authors.forename: Jenny
authors.initials: J
authors.lastname: Hu
authors.affiliation: University of Florida College of Medicine-Jacksonville, Jacksonville, Florida.
authors.forename: Megha
authors.initials: M
authors.lastname: Kureti
authors.affiliation: University of Florida College of Medicine-Jacksonville, Jacksonville, Florida.
authors.forename: Niti
authors.initials: N
authors.lastname: Aggarwal
authors.affiliation: University of Florida College of Medicine-Jacksonville, Jacksonville, Florida.
authors.forename: Ashwin
authors.initials: A
authors.lastname: Durairaj
authors.affiliation: University of Florida College of Medicine-Jacksonville, Jacksonville, Florida.
authors.forename: Latonya
authors.initials: L
authors.lastname: Been
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: Siva
authors.initials: S
authors.lastname: Suryadevara
authors.affiliation: University of Florida College of Medicine-Jacksonville, Jacksonville, Florida.
authors.forename: Patrick
authors.initials: P
authors.lastname: Antoun
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 / Q000000981:diagnostic imaging / Q000628:therapy*; D000241:Adenosine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D000328:Adult; D000368:Aged; D001241:Aspirin / Q000008:administration & dosage; D015415:Biomarkers / Q000097:blood; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000097:blood; D004334:Drug Administration Schedule; D057915:Drug Substitution; D004359:Drug Therapy, Combination; D005260:Female; D005431:Florida; D006801:Humans; D008297:Male; D008840:Microfilament Proteins / Q000097:blood; D008875:Middle Aged; D062645:Percutaneous Coronary Intervention / Q000009:adverse effects; D010750:Phosphoproteins / Q000097:blood; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D010979:Platelet Function Tests; D000068799:Prasugrel Hydrochloride / Q000008:administration & dosage* / Q000009:adverse effects; 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; D000068799:Prasugrel Hydrochloride; D000077486:Ticagrelor; D000241:Adenosine; D001241:Aspirin
keywords: platelet reactivity; prasugrel; switching; ticagrelor