title: Increased platelet inhibition after switching from maintenance clopidogrel to prasugrel in Japanese patients with stable coronary artery disease.
abstract: BACKGROUND
  The pharmacodynamic effects of changing from standard-dose clopidogrel to low-dose (3.75 mg) prasugrel in Japanese patients are largely unknown.
  
  
  RESULTS
  A total of 53 consecutive Japanese patients with stable coronary artery disease (CAD) who received aspirin and clopidogrel were enrolled. Clopidogrel was switched to 3.75 mg prasugrel. At day 14, prasugrel was switched to 75 mg clopidogrel. Platelet reactivity was measured using the VerifyNow assay at baseline, day 14, and day 28. VerifyNow P2Y12 reaction units (PRU) >208 was defined as high on-treatment platelet reactivity (HPR). The prevalence of HPR (18.9% vs. 41.5% vs. 44.2%, P<0.001) and the PRU level (154.3±54.2 vs. 196.2±55.5 vs. 194.6±55.8, P<0.001) were significantly lower on prasugrel maintenance therapy compared with the clopidogrel therapy before and after switching. The CYP2C19 genotypes that account for the 3 phenotypes (ie, extensive metabolizer, intermediate metabolizer, and poor metabolizer) had a significant impact on platelet reactivity with clopidogrel (174.9±54.0 vs. 193.1±56.5 vs. 240.6±25.4 PRU, P<0.001) but not prasugrel (147.0±51.9 vs. 147.5±58.3 vs. 184.4±38.3 PRU, P=0.15).
  
  
  CONCLUSIONS
  Low-dose prasugrel achieves stronger platelet inhibition than clopidogrel in Japanese patients with stable CAD.
authors: Department of Cardiovascular Medicine, Chiba University Graduate School of Medicine.
authors: Takeshi
authors: T
authors: Nishi
authors: Noritaka
authors: N
authors: Ariyoshi
authors: Takashi
authors: T
authors: Nakayama
authors: Yoshihide
authors: Y
authors: Fujimoto
authors: Kazumasa
authors: K
authors: Sugimoto
authors: Masayuki
authors: M
authors: Takahara
authors: Shinichi
authors: S
authors: Wakabayashi
authors: Masaya
authors: M
authors: Koshizaka
authors: Hideki
authors: H
authors: Hanaoka
authors: Yoshio
authors: Y
authors: Kobayashi
mesh_terms: D000368:Aged; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D000077144:Clopidogrel; D003324:Coronary Artery Disease / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D065731:Cytochrome P-450 CYP2C19 / Q000235:genetics / Q000378:metabolism; D004334:Drug Administration Schedule; D057915:Drug Substitution; D005260:Female; D005838:Genotype; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage* / Q000378:metabolism; D010979:Platelet Function Tests; D000068799:Prasugrel Hydrochloride / Q000008:administration & dosage* / Q000378:metabolism; D011446:Prospective Studies; D058921:Purinergic P2Y Receptor Antagonists / Q000008:administration & dosage* / Q000378:metabolism; D058925:Receptors, Purinergic P2Y12 / Q000097:blood / Q000187:drug effects; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: C548576:P2RY12 protein, human; D010975:Platelet Aggregation Inhibitors; D058921:Purinergic P2Y Receptor Antagonists; D058925:Receptors, Purinergic P2Y12; D000077144:Clopidogrel; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D000068799:Prasugrel Hydrochloride; D013988:Ticlopidine