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Impact of Cigarette Smoking on P2Y12 Receptor Binding Activity Before and After Clopidogrel Therapy in Patients with Coronary Artery Disease

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Abstract

Smoking enhances the P2Y12 receptor inhibitory effects of clopidogrel. Nicotine increases P2Y12 receptor expression in platelet lysates from healthy volunteers. However, the impact of cigarette smoking on platelet P2Y12 receptor binding in clopidogrel-treated patients with coronary artery disease (CAD) is unknown. Clopidogrel-naïve patients with stable CAD (n = 20) were enrolled and stratified according to smoking status. P2Y12 receptor binding activity was determined by radioligand receptor binding prior and 24 h after a 600-mg loading dose of clopidogrel. Baseline P2Y12 receptor binding was 1.8-fold higher in smokers compared with nonsmokers. After a 600-mg loading dose of clopidogrel, smokers showed a 6.4-fold reduction in P2Y12 receptor binding indicative of marked clopidogrel-mediated blockade, while there were minimal changes among nonsmokers. Among patients with stable CAD, smokers have more P2Y12 receptor binding than nonsmokers and have a higher degree of clopidogrel-mediated platelet inhibition.

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Source of Funding

The present study was funded by an Institutional Grant of the University of Florida College of Medicine-Jacksonville and by a grant provided by The James and Esther King Biomedical Research Program (1KN01-33989).

Conflict of Interest

Jung Rae Cho, Bhaloo Desai, Michael J. Haas, Fabiana Rollini, Francesco Franchi, Ana Muñiz-Lozano, Antonio Tello-Montoliu, Elisabetta Ferrante, Luis A. Guzman, and Theodore A. Bass have no conflict of interest to report. Dominick J. Angiolillo received payment as an individual for (a) consulting fee or honorarium from Bristol Myers Squibb, Sanofi-Aventis, Eli Lilly, Daiichi Sankyo, The Medicines Company, AstraZeneca, Merck, Evolva, Abbott Vascular, and PLx Pharma and (b) participation in review activities from Johnson & Johnson, St. Jude, and Sunovion. Institutional payments for grants from Bristol Myers Squibb, Sanofi-Aventis, Glaxo Smith Kline, Otsuka, Eli Lilly, Daiichi Sankyo, The Medicines Company, AstraZeneca, Evolva, Gilead and has other financial relationships with Esther and King Biomedical Research Grant.

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  1. University of Florida College of Medicine-Jacksonville, 655 West 8th Street, Jacksonville, FL, 32209, USA

    Jung Rae Cho, Bhaloo Desai, Michael J. Haas, Fabiana Rollini, Francesco Franchi, Ana Muñiz-Lozano, Antonio Tello-Montoliu, Elisabetta Ferrante, Luis A. Guzman, Theodore A. Bass & Dominick J. Angiolillo

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  1. Jung Rae Cho
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  2. Bhaloo Desai
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Correspondence to Dominick J. Angiolillo.

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Associate Editor Emanuele Barbato oversaw the review of this article

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Cho, J.R., Desai, B., Haas, M.J. et al. Impact of Cigarette Smoking on P2Y12 Receptor Binding Activity Before and After Clopidogrel Therapy in Patients with Coronary Artery Disease. J. of Cardiovasc. Trans. Res. 7, 47–52 (2014). https://doi.org/10.1007/s12265-013-9530-8

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