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. Patients and 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 mu mol/L ADP-stimulated IPA (P=0.006), and had a trend toward a greater value of 20 mu mol/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 mu mol/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 P2Y12 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 mu mol/L ADP-induced PR; odds ratio 4.651, 95% confidence interval 1.181-18.519, P=0.028). Conclusion: 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. (C) 2010 Elsevier Ltd. All rights reserved.