title: Enhanced clopidogrel response in smokers is reversed after discontinuation as assessed by VerifyNow assay: additional evidence for the concept of 'smokers' paradox'.
abstract: BACKGROUND
  Previous reports on smokers' paradox to clopidogrel have only been able to show an association between cigarette smoking and enhanced response to clopidogrel therapy. No study has shown reversal of enhanced clopidogrel response after smoking cessation.
  
  
  OBJECTIVE
  To conduct a prospective observational longitudinal study in order to measure the impact of cigarette smoking on on-clopidogrel platelet reactivity (OPR).
  
  
  METHODS
  From the prospective CROSS-VERIFY cohort, 810 subjects with repeated measurement of OPR at least 1 month apart were analysed. With smoking status ascertained at two time points, baseline and follow-up, study subjects were categorised into never smokers (n=628), smoking quitters (n=77) and persistent smokers (n=105). Dependent variables included OPR measured by the VerifyNow assay and the percentage of subjects with high OPR (HOPR).
  
  
  RESULTS
  At baseline, current smokers showed significantly lower OPR compared with never smokers, with no significant differences in OPR between future quitters and future persistent smokers within current smokers. While the OPR of never smokers and persistent smokers did not change significantly during the follow-up, the mean OPR of quitters increased significantly by 19 P2Y12 reaction units (p=0.013). The frequency of HOPR showed similar results, with an 8-10% increase in smoking quitters in contrast to no significant changes in never and persistent smokers. Both mean OPR and the frequency of HOPR showed a linear inverse relationship with the amount of smoking.
  
  
  CONCLUSIONS
  Enhanced clopidogrel response in smokers is reversed after smoking discontinuation, suggesting a causal relationship in addition to the previously reported association between smoking and enhanced clopidogrel response.
authors.affiliation: Department of Internal Medicine and Cardiovascular Center, Seoul National University Hospital, Seoul, Korea.
authors.forename: Kyung Woo
authors.initials: KW
authors.lastname: Park
authors.forename: Si-Hyuck
authors.initials: SH
authors.lastname: Kang
authors.forename: Jeehoon
authors.initials: J
authors.lastname: Kang
authors.forename: Ki-Hyun
authors.initials: KH
authors.lastname: Jeon
authors.forename: Jin Joo
authors.initials: JJ
authors.lastname: Park
authors.forename: Jung-Kyu
authors.initials: JK
authors.lastname: Han
authors.forename: Jin-Sin
authors.initials: JS
authors.lastname: Koh
authors.forename: Sang Eun
authors.initials: SE
authors.lastname: Lee
authors.forename: Han-Mo
authors.initials: HM
authors.lastname: Yang
authors.forename: Hae-Young
authors.initials: HY
authors.lastname: Lee
authors.forename: Hyun-Jae
authors.initials: HJ
authors.lastname: Kang
authors.forename: Bon-Kwon
authors.initials: BK
authors.lastname: Koo
authors.forename: Byung-Hee
authors.initials: BH
authors.lastname: Oh
authors.forename: Young-Bae
authors.initials: YB
authors.lastname: Park
authors.forename: Hyo-Soo
authors.initials: HS
authors.lastname: Kim
mesh_terms: D000368:Aged; D001792:Blood Platelets / Q000187:drug effects*; D000077144:Clopidogrel; D017023:Coronary Angiography; D004351:Drug Resistance; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000097:blood / Q000000981:diagnostic imaging / Q000188:drug therapy*; D015539:Platelet Activation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage; D011446:Prospective Studies; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects*; D016540:Smoking Cessation; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D016896:Treatment Outcome
chemical_list: D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D013988:Ticlopidine