title: Impact of smoking on antiplatelet effect of clopidogrel and prasugrel after loading dose and on maintenance therapy.
abstract: BACKGROUND
  Pharmacodynamic studies reported an amplified on-clopidogrel platelet inhibition in smokers potentially caused by an increased metabolic drug activation via induction of cytochrome P450 1A2. The aims of this analysis were to evaluate the impact of smoking on the antiplatelet effect of clopidogrel and prasugrel and to test the potential interaction of smoking with the treatment effect of these drugs.
  
  
  METHODS
  A variety of platelet function results was analyzed from 2 large cohorts of patients undergoing coronary intervention after loading with clopidogrel 600 mg (n = 2,533 and n = 1,996), a cohort of patients undergoing dose adaptation from 75 to 150 mg according to response to clopidogrel (n = 117) and a crossover trial comparing clopidogrel 150 mg with prasugrel 10 mg (n = 87). Linear regression analyses were used to test the impact of smoking on platelet function and to identify independent predictors of on-treatment platelet reactivity. The potential interaction of smoking with the clinical effect of clopidogrel versus prasugrel was analyzed in the TRITON-TIMI 38 cohort (n = 13,608).
  
  
  RESULTS
  No significant association of smoking with platelet reactivity on clopidogrel was seen in unadjusted and adjusted analyses. The variables most consistently associated with on-clopidogrel platelet function were age, sex, diabetes, and body mass index. There was no significant interaction of smoking status at presentation with the clinical efficacy of prasugrel versus clopidogrel (P for interaction = .39).
  
  
  CONCLUSIONS
  Smoking does not impact on platelet reactivity in patients after loading or on different maintenance doses of clopidogrel. The clinical treatment effect of clopidogrel versus prasugrel is not affected by smoking status at presentation.
authors: TIMI Study Group, Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA. whochholzer@partners.org
authors: Willibald
authors: W
authors: Hochholzer
authors: Dietmar
authors: D
authors: Trenk
authors: Jessica L
authors: JL
authors: Mega
authors: Tanja
authors: T
authors: Morath
authors: Christian
authors: C
authors: Stratz
authors: Christian M
authors: CM
authors: Valina
authors: Michelle L
authors: ML
authors: O'Donoghue
authors: Isabell
authors: I
authors: Bernlochner
authors: Charles F
authors: CF
authors: Contant
authors: Jianping
authors: J
authors: Guo
authors: Marc S
authors: MS
authors: Sabatine
authors: Albert
authors: A
authors: Schömig
authors: Franz-Josef
authors: FJ
authors: Neumann
authors: Adnan
authors: A
authors: Kastrati
authors: Stephen D
authors: SD
authors: Wiviott
authors: Dirk
authors: D
authors: Sibbing
mesh_terms: D000368:Aged; D001792:Blood Platelets / Q000502:physiology; D000077144:Clopidogrel; D003324:Coronary Artery Disease / Q000097:blood / Q000188:drug therapy* / Q000209:etiology; D018592:Cross-Over Studies; D019388:Cytochrome P-450 CYP1A2 / Q000097:blood; D004305:Dose-Response Relationship, Drug; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000008:administration & dosage* / Q000493:pharmacokinetics; D010974:Platelet Aggregation / Q000502:physiology; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics; D000068799:Prasugrel Hydrochloride; D058921:Purinergic P2Y Receptor Antagonists / Q000008:administration & dosage / Q000493:pharmacokinetics; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects* / Q000097:blood; D013876:Thiophenes / Q000008:administration & dosage* / Q000493:pharmacokinetics; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D010879:Piperazines; D010975:Platelet Aggregation Inhibitors; D058921:Purinergic P2Y Receptor Antagonists; D013876:Thiophenes; D000077144:Clopidogrel; D019388:Cytochrome P-450 CYP1A2; D000068799:Prasugrel Hydrochloride; D013988:Ticlopidine