title: Prasugrel achieves greater inhibition of platelet aggregation and a lower rate of non-responders compared with clopidogrel in aspirin-treated patients with stable coronary artery disease.
abstract: OBJECTIVE
  This study was designed to compare the degree of inhibition of platelet aggregation (IPA) of prasugrel with that of clopidogrel in stable aspirin-treated patients with coronary artery disease (CAD).
  
  
  RESULTS
  Subjects (n=101) were randomly assigned to the following loading dose (LD) (day 1)/maintenance dose (MD) (days 2-28) combinations: prasugrel, 40 mg/5 mg; 40 mg/7.5 mg; 60 mg/10 mg; 60 mg/15 mg; or clopidogrel, 300 mg/75 mg. Turbidometric platelet aggregation was measured at multiple timepoints during the study. At 4 h after dosing, with 20 microM ADP, both prasugrel LDs achieved significantly higher mean IPA levels (60.6% and 68.4 vs. 30.0%, respectively; all P<0.0001) and lower percentage (3 vs. 52%, P<0.0001) of pharmacodynamic non-responders (defined as IPA <20%) than clopidogrel. Prasugrel 10 and 15 mg MDs achieved consistently higher mean IPA than clopidogrel 75 mg at day 28 (all P<0.0001). At pre-MD on day 28, there were no non-responders in the 10 and 15 mg prasugrel group, compared with 45% in the clopidogrel group (P=0.0007).
  
  
  CONCLUSIONS
  In this population, prasugrel (40-60 mg LD and 10-15 mg MD) achieves greater IPA and a lower proportion of pharmacodynamic non-responders compared with the approved clopidogrel dosing.
authors.affiliation: Department of Medical Sciences, Cardiology and Uppsala Clinical Research Center, University Hospital, 751 85 Uppsala, Sweden.
authors.forename: Tomas
authors.initials: T
authors.lastname: Jernberg
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Payne
authors.forename: Kenneth J
authors.initials: KJ
authors.lastname: Winters
authors.forename: Christelle
authors.initials: C
authors.lastname: Darstein
authors.forename: John T
authors.initials: JT
authors.lastname: Brandt
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Jakubowski
authors.forename: Hideo
authors.initials: H
authors.lastname: Naganuma
authors.forename: Agneta
authors.initials: A
authors.lastname: Siegbahn
authors.forename: Lars
authors.initials: L
authors.lastname: Wallentin
mesh_terms: D000328:Adult; D000368:Aged; D001241:Aspirin / Q000008:administration & dosage* / Q000009:adverse effects; D000077144:Clopidogrel; D003324:Coronary Artery Disease / Q000188:drug therapy*; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000008:administration & dosage* / Q000009:adverse effects; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D000068799:Prasugrel Hydrochloride; D013876:Thiophenes / Q000008:administration & dosage* / Q000009:adverse effects; D013988:Ticlopidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*
chemical_list: D010879:Piperazines; D010975:Platelet Aggregation Inhibitors; D013876:Thiophenes; D000077144:Clopidogrel; D000068799:Prasugrel Hydrochloride; D013988:Ticlopidine; D001241:Aspirin