title: Smoking at least 10 cigarettes per day increases platelet inhibition by clopidogrel in patients with ST-segment-elevation myocardial infarction.
abstract: BACKGROUND
  Recent data suggest that cigarette smoking (CS) might decrease the risk of cardiovascular events in patients with ST-segment-elevation myocardial infarction (STEMI) or established cardiovascular disease. Although it may be related to the effect of CS on the metabolism of clopidogrel, the association between the extent of CS and clopidogrel-induced platelet inhibition has not been well defined.
  
  
  METHODS
  We tested the association between smoking status and inhibition of platelet aggregation (IPA) in response to a clopidogrel loading of 600-mg in 20 healthy subjects. We then enrolled 138 consecutive STEMI patients treated with primary coronary stenting. On-clopidogrel platelet reactivity (PR) was assessed with conventional aggregometry and the VerifyNow P2Y(12) assay, according to smoking status.
  
  
  RESULTS
  After 6 hours post-loading in healthy subjects, CS patients on ≥10 cigarettes/day showed a significantly higher value of 5 μmol/L ADP-stimulated IPA (P=0.006), and had a trend toward a greater value of 20 μmol/L ADP-stimulated IPA (P=0.093) compared with non-smokers. In STEMI patients, there was no difference in PR between non-smokers (n=66) and CS patients<10 cigarettes/day (n=16). CS patients on ≥10 cigarettes/day (n=56) demonstrated lower PR with 5 and 20 μmol/L ADP (40.9±16.1% versus 46.6±11.7%, P=0.028, and 53.8±16.6% versus 59.2±12.2%, P=0.040, respectively) and lower P2Y(12) reaction units (204±85 versus 270±69, P<0.001) than non-smokers. On multivariate analyses, CS≥10 cigarettes/day was the only predictor of low on-clopidogrel PR (≤33%; the lowest quartile of 5 μmol/L ADP-induced PR; odds ratio 4.651, 95% confidence interval 1.181-18.519, P=0.028).
  
  
  CONCLUSIONS
  CS seems to increase antiplatelet response to clopidogrel in healthy volunteers and STEMI patients. Smoking 10 or more cigarettes/day can significantly decrease on-clopidogrel platelet reactivity in these populations.
authors.affiliation: Division of Cardiology, Department of Internal Medicine, Gyeongsang National University Hospital, 90 Chiram-dong, Jinju, 660-702, Gyeongsangnam-do, South Korea. goodoctor@naver.com
authors.forename: Young-Hoon
authors.initials: YH
authors.lastname: Jeong
authors.forename: Jung-Hyun
authors.initials: JH
authors.lastname: Cho
authors.forename: Min-Kyung
authors.initials: MK
authors.lastname: Kang
authors.forename: Jin-Sin
authors.initials: JS
authors.lastname: Koh
authors.forename: In-Suk
authors.initials: IS
authors.lastname: Kim
authors.forename: Yongwhi
authors.initials: Y
authors.lastname: Park
authors.forename: Seok-Jae
authors.initials: SJ
authors.lastname: Hwang
authors.forename: Choong Hwan
authors.initials: CH
authors.lastname: Kwak
authors.forename: Jin-Yong
authors.initials: JY
authors.lastname: Hwang
mesh_terms: D000328:Adult; D000368:Aged; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism; D000077144:Clopidogrel; D005260:Female; D006801:Humans; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy*; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D012907:Smoking / Q000009:adverse effects*; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D013988:Ticlopidine