title: Inhibitory effects of ticagrelor compared with clopidogrel on platelet function in patients with acute coronary syndromes: the PLATO (PLATelet inhibition and patient Outcomes) PLATELET substudy.
abstract: OBJECTIVE
  The PLATO (PLATelet inhibition and patient Outcomes) PLATELET substudy aimed to compare the antiplatelet effects of clopidogrel and ticagrelor in patients with acute coronary syndromes.
  
  
  BACKGROUND
  The PLATO study demonstrated superiority of ticagrelor over clopidogrel in the prevention of ischemic events in patients with acute coronary syndromes.
  
  
  METHODS
  Patients were randomized to receive either clopidogrel (300- to 600-mg loading dose [LD], 75 mg/day) or ticagrelor (180-mg LD, 90 mg twice daily). The effects of maintenance therapy were studied in 69 patients pre- and 2 to 4 h post-dose after at least 28 days. The LD effect was studied in 24 clopidogrel-naive patients. Light transmittance aggregometry (adenosine diphosphate 5 to 20 μM), VerifyNow P2Y12, and VASP phosphorylation assays were performed.
  
  
  RESULTS
  During maintenance therapy, ticagrelor achieved greater suppression of platelet reactivity compared with clopidogrel. The mean maximum light transmittance aggregometry responses (adenosine diphosphate 20 μM) post-maintenance dose were 44±15% for clopidogrel and 28±10% for ticagrelor (p<0.001). High platelet reactivity was seen more frequently in the clopidogrel group. Proton pump inhibitor use was associated with higher platelet reactivity with clopidogrel but not ticagrelor. The ticagrelor LD also achieved greater inhibition of platelet aggregation compared with the clopidogrel LD.
  
  
  CONCLUSIONS
  Ticagrelor achieves greater antiplatelet effect than clopidogrel in patients with acute coronary syndromes, both in the first hours of treatment and during maintenance therapy.
authors.affiliation: Department of Cardiovascular Science, University of Sheffield, and NIHR Cardiovascular Biomedical Research Unit, Sheffield, United Kingdom. r.f.storey@sheffield.ac.uk
authors.forename: Robert F
authors.initials: RF
authors.lastname: Storey
authors.forename: Dominick J
authors.initials: DJ
authors.lastname: Angiolillo
authors.forename: Shankar B
authors.initials: SB
authors.lastname: Patil
authors.forename: Bhaloo
authors.initials: B
authors.lastname: Desai
authors.forename: Rosemary
authors.initials: R
authors.lastname: Ecob
authors.forename: Steen
authors.initials: S
authors.lastname: Husted
authors.forename: Hakan
authors.initials: H
authors.lastname: Emanuelsson
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Cannon
authors.forename: Richard C
authors.initials: RC
authors.lastname: Becker
authors.forename: Lars
authors.initials: L
authors.lastname: Wallentin
mesh_terms: D054058:Acute Coronary Syndrome / Q000188:drug therapy* / Q000503:physiopathology; D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D000368:Aged; D001792:Blood Platelets / Q000187:drug effects* / Q000502:physiology*; D000077144:Clopidogrel; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D000077486:Ticagrelor; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D000077486:Ticagrelor; D000241:Adenosine; D013988:Ticlopidine