Journal
JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
Volume 53, Issue 15, Pages 1273-1278Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.jacc.2008.12.044
Keywords
clopidogrel; cytochrome P450; smoking
Categories
Funding
- Bristol-Myers Squibb
- AstraZeneca
- Bayer Healthcare
- Beckman Coulter
- Biosite
- CV Therapeutics
- Eli Lilly
- Genentech
- GlaxoSmithKline
- Integrated Therapeutics Group
- Johnson Johnson
- Merck
- Nanosphere
- Novartis
- Pfizer
- Roche Diagnostics
- Sanofi-Aventis
- Schering-Plough
- Siemens Medical Solutions
- Accumetrics
- Bristol Myers Squibb/Sanofi Pharmaceuticals Partnership
- Merck/Schering-Plough Partnership
- Sanofi-Aventis and Schering-Plough
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Objectives The aim of this study was to examine the interaction between cigarette smoking and the clinical efficacy of clopidogrel in ST-segment elevation myocardial infarction (STEMI). Background Cigarette smoking induces cytochrome P450 (CYP)1A2, which converts clopidogrel into its active metabolite, and prior studies suggest greater inhibition of platelet aggregation by clopidogrel in smokers of >= 10 cigarettes/day. Methods The effect of clopidogrel compared with placebo on angiographic and clinical outcomes was examined in 3,429 STEMI patients in the CLARITY-TIMI 28 (Clopidogrel as Adjunctive Reperfusion Therapy-Thrombolysis In Myocardial Infarction 28) randomized trial stratified by smoking intensity as follows: not current smokers (n = 1,732), and smokers of 1 to 9 (n = 206), 10 to 19 (n = 354), 20 to 29 (n = 715), and >= 30 cigarettes/day (n = 422). Logistic regression was used to adjust for other baseline characteristics and interaction terms to test for effect modification. Results Although clopidogrel reduced the rate of the primary end point of a closed infarct-related artery or death/myocardial infarction before angiography in the CLARITY-TIMI 28 trial, the benefit was especially marked among those who smoked >= 10 cigarettes/day (adjusted odds ratio [OR]: 0.49, 95% confidence interval [CI]: 0.37 to 0.66; p < 0.0001) compared with those who did not (adjusted OR: 0.72, 95% CI: 0.57 to 0.91; p = 0.006; p(interaction) = 0.04). Similarly, clopidogrel was significantly more effective at reducing the rate of cardiovascular death, myocardial infarction, or urgent revascularization through 30 days among those who smoked >= 10 cigarettes/ day (adjusted OR: 0.54, 95% CI: 0.38 to 0.76; p = 0.0004) compared with those who did not (adjusted OR: 0.98; 95% CI: 0.75 to 1.28; p = 0.87; p(interaction) = 0.006). Conclusions Cigarette smoking seems to positively modify the beneficial effect of clopidogrel on angiographic and clinical outcomes. This study demonstrates that common clinical factors that influence the metabolism of clopidogrel might impact its clinical effectiveness. (J Am Coll Cardiol 2009; 53: 1273-8) (c) 2009 by the American College of Cardiology Foundation
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