title: Prasugrel overcomes high on-clopidogrel platelet reactivity in the acute phase of acute coronary syndrome and maintains its antiplatelet potency at 30-day follow-up.
abstract: BACKGROUND
  The aim of this study was to assess antiplatelet effect of prasugrel in acute coronary syndrome (ACS) patients with high on-treatment platelet reactivity (HTPR) on clopidogrel, undergoing percutaneous coronary intervention (PCI).
  
  
  METHODS
  A prospective, platelet reactivity-guided, parallel-group, open-label study including 71 patients pretreated with clopidogrel 600 mg and assigned either to prasugrel (30 mg loading dose, 10 mg maintenance dose; n = 46) or clopidogrel (150 mg maintenance dose for 6 days and thereafter 75 mg maintenance dose; n = 25) regimen, based on vasodilator-stimulated phosphoprotein (VASP)-assessed platelet reactivity index (PRI; > 50% vs. ≤ 50%) measured next morning post-PCI.
  
  
  RESULTS
  Median PRI value after switch to prasugrel sharply declined at 24 h (70.0 [61.3-75.6] vs. 11.9 [6.8-25.7]%; p < 0.000001) and slightly but significantly rose between 24 h and 30 days (27.9 [15.5-46.8]%; p < 0.0006). In contrast, median PRI values in the clopidogrel group were similar at baseline and at 24 h (25.1 [13.7-40.2] vs. 22.0 [18.4-36.8]%; p = NS) and then modestly rose at 30 days (30.3 [20.4-45.7]%; p < 0.03). The prevalence of HTPR decreased in the prasugrel group between baseline and 24 h measurements (100.0 vs. 4.3%; p < 0.0001). Rates of patients with HTPR at 24 h and 30 days were similar in both groups, so were the tendencies in patterns of platelet inhibition evaluated with multiple electrode aggregometry as compared with the VASP assay.
  
  
  CONCLUSIONS
  Our study indicates that prasugrel overcomes HTPR on clopidogrel in the acute phase of interventionally treated ACS and maintains its antiplatelet potency in 30-day follow-up. Potential clinical benefits of personalized antiplatelet prasugrel-based therapy warrant further investigation in clinical ACS trials.
authors.affiliation: Department of Cardiology and Inter nal Medicine, Collegium Medicum, Nicolaus Copernicus University, Bydgoszcz, Poland. marekkozinski@wp.pl.
authors.forename: Marek
authors.initials: M
authors.lastname: Koziński
authors.forename: Karolina
authors.initials: K
authors.lastname: Obońska
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Stankowska
authors.forename: Eliano Pio
authors.initials: EP
authors.lastname: Navarese
authors.forename: Tomasz
authors.initials: T
authors.lastname: Fabiszak
authors.forename: Wioleta
authors.initials: W
authors.lastname: Stolarek
authors.forename: Michał
authors.initials: M
authors.lastname: Kasprzak
authors.forename: Jolanta Maria
authors.initials: JM
authors.lastname: Siller-Matula
authors.forename: Danuta
authors.initials: D
authors.lastname: Rość
authors.forename: Jacek
authors.initials: J
authors.lastname: Kubica
authors.forename: Stefano
authors.initials: S
authors.lastname: De Servi
mesh_terms: D054058:Acute Coronary Syndrome / Q000097:blood / Q000000981:diagnostic imaging / Q000628:therapy*; D000293:Adolescent; D000328:Adult; D000368:Aged; D001792:Blood Platelets / Q000187:drug effects*; D000077144:Clopidogrel; D017023:Coronary Angiography; D004305:Dose-Response Relationship, Drug; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage; D000068799:Prasugrel Hydrochloride / Q000008:administration & dosage*; D011446:Prospective Studies; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D000068799:Prasugrel Hydrochloride; D013988:Ticlopidine