title: Onset of antiplatelet action with high (100 mg) versus standard (60 mg) loading dose of prasugrel in patients with ST-segment-elevation myocardial infarction undergoing primary percutaneous coronary intervention: pharmacodynamic study.
abstract: BACKGROUND
  In patients with ST-segment-elevation myocardial infarction undergoing primary percutaneous coronary intervention, a suboptimal degree of platelet inhibition for the first 2 hours after the standard 60 mg loading dose of prasugrel has been described.
  
  
  RESULTS
  In a prospective, 3-center, nonrandomized, controlled study, 2 sequential groups of P2Y12 inhibitor-naive consecutive patients were loaded with either 100 mg (n=47) or 60 mg (n=35) of prasugrel. Platelet reactivity was assessed by VerifyNow at hours 0, 0.5, 1, 2, and 4. At hour 2, there was a strong trend for the primary end point of platelet reactivity (in P2Y12 reaction units) to be lower (least squares estimates of the mean difference [95% confidence interval], -45.5 [-91.2 to 0.3]; P=0.051), whereas platelet reactivity percentage inhibition (median, first to third quartile) was higher (75.5% [24%-91.8%] versus 23.5% [0%-78.3%]; P=0.02) in the 100-mg compared with 60-mg loading dose group. At hour 2, prasugrel 100 mg over 60 mg loading dose significantly reduced high platelet reactivity rates from 28.6% to 8.5% (≥230 P2Y12 reaction units threshold; P=0.036) and from 31.4% to 10.6% (≥208 P2Y12 reaction units threshold; P=0.024), whereas resulted in lower rate of ≤20% platelet inhibition (23.4% versus 51.4%; P=0.009).
  
  
  CONCLUSIONS
  In patients with ST-segment-elevation myocardial infarction treated with primary percutaneous coronary intervention, a higher (100 mg) than the standard loading dose of prasugrel results in greater and more consistent platelet inhibition, yet this will need to be further validated in additional studies.
  
  
  BACKGROUND
  http://www.clinicaltrials.gov. Unique identifier: NCT01835353.
authors.affiliation: From the Department of Cardiology, Patras University Hospital, Rion, Patras, Greece (D.A., G.M., I.X., V.G., A.P., G.T., N.K., G.H., P.D.); Department of Cardiology, Konstantopoulio General Hospital, Athens, Greece (S.P., S.K.); and Department of Cardiology, Athens General Hospital "G. Gennimatas," Athens, Greece (S.D., C.A.).
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Alexopoulos
authors.forename: George
authors.initials: G
authors.lastname: Makris
authors.forename: Ioanna
authors.initials: I
authors.lastname: Xanthopoulou
authors.forename: Sotirios
authors.initials: S
authors.lastname: Patsilinakos
authors.forename: Spyridon
authors.initials: S
authors.lastname: Deftereos
authors.forename: Vassilios
authors.initials: V
authors.lastname: Gkizas
authors.forename: Angelos
authors.initials: A
authors.lastname: Perperis
authors.forename: Stavros
authors.initials: S
authors.lastname: Karanikas
authors.forename: Christos
authors.initials: C
authors.lastname: Angelidis
authors.forename: Grigorios
authors.initials: G
authors.lastname: Tsigkas
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Koutsogiannis
authors.forename: George
authors.initials: G
authors.lastname: Hahalis
authors.forename: Periklis
authors.initials: P
authors.lastname: Davlouros
mesh_terms: D000328:Adult; D000368:Aged; D001777:Blood Coagulation / Q000187:drug effects; D001792:Blood Platelets / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004562:Electrocardiography; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood* / Q000628:therapy*; D062645:Percutaneous Coronary Intervention; D010879:Piperazines / Q000493:pharmacokinetics* / Q000494:pharmacology; D015539:Platelet Activation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000493:pharmacokinetics* / Q000494:pharmacology; D000068799:Prasugrel Hydrochloride; D011446:Prospective Studies; D013876:Thiophenes / Q000493:pharmacokinetics* / Q000494:pharmacology; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D010879:Piperazines; D010975:Platelet Aggregation Inhibitors; D013876:Thiophenes; D000068799:Prasugrel Hydrochloride
keywords: myocardial infarction; percutaneous coronary intervention; prasugrel