Smoking at least 10 cigarettes per day increases platelet inhibition by clopidogrel in patients with ST-segment-elevation myocardial infarction.
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.
Jeong
Young-Hoon
YH
Division of Cardiology, Department of Internal Medicine, Gyeongsang National University Hospital, 90 Chiram-dong, Jinju, 660-702, Gyeongsangnam-do, South Korea. goodoctor@naver.com
Cho
Jung-Hyun
JH
Kang
Min-Kyung
MK
Koh
Jin-Sin
JS
Kim
In-Suk
IS
Park
Yongwhi
Y
Hwang
Seok-Jae
SJ
Kwak
Choong Hwan
CH
Hwang
Jin-Yong
JY
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
D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D013988:Ticlopidine