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Journal of Cardiovascular Translational Research

Published in:

01-02-2014

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

Authors: 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

Published in: Journal of Cardiovascular Translational Research | Issue 1/2014

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.

Levine, G. N., Bates, E. R., Blankenship, J. C., Bailey, S. R., Bittl, J. A., Cercek, B., et al. (2011). 2011 ACCF/AHA/SCAI Guideline for Percutaneous Coronary Intervention: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines and the Society for Cardiovascular Angiography and Interventions. Circulation, 124, e574–e651.PubMedCrossRef

Angiolillo, D. J., Fernandez-Ortiz, A., Bernardo, E., Alfonso, F., Macaya, C., Bass, T. A., et al. (2007). Variability in individual responsiveness to clopidogrel: clinical implications, management and future perspectives. Journal of the American College of Cardiology, 49, 1505–1516.PubMedCrossRef

Nusca, A., Patti, G., & Di Sciascio, G. (2013). Influence of platelet reactivity on clinical outcome of patients with stable coronary artery disease. Journal of Cardiovascular Translational Research, 6, 346–354.PubMedCrossRef

Orban, M., & Sibbing, D. (2013). Platelet function testing in patients with acute coronary syndrome. Journal of Cardiovascular Translational Research, 6, 371–377.PubMedCrossRef

Zhao ZG, Chen M, Peng Y, Chai H, Liu W, Li Q, Ren X, Wang XQ, Luo XL, Zhang C, Huang DJ (2013) The impact of smoking on clinical efficacy and pharmacodynamic effects of clopidogrel: a systematic review and meta-analysis. Heart. doi:10.1136/heartjnl-2013-304138.

Gagne, J. J., Bykov, K., Choudhry, N. K., Toomey, T. J., Connolly, J. G., & Avorn, J. (2013). Effect of smoking on comparative efficacy of antiplatelet agents: systematic review, meta-analysis, and indirect comparison. BMJ, 347, f5307.PubMedCentralPubMedCrossRef

Gurbel, P. A., Nolin, T. D., & Tantry, U. S. (2012). Clopidogrel efficacy and cigarette smoking status. JAMA, 307, 2495–2496.PubMedCrossRef

Desai, N. R., Mega, J. L., Jiang, S., Cannon, C. P., & Sabatine, M. S. (2009). Interaction between cigarette smoking and clinical benefit of clopidogrel. Journal of the American College of Cardiology, 53, 1273–1278.PubMedCentralPubMedCrossRef

Berger, J. S., Bhatt, D. L., Steinhubl, S. R., Shao, M., Steg, P. G., Montalescot, G., et al. (2009). Smoking, clopidogrel, and mortality in patients with established cardiovascular disease. Circulation, 120, 2337–2344.PubMedCentralPubMedCrossRef

10.

Mehta, S. R., Tanguay, J. F., Eikelboom, J. W., Jolly, S. S., Joyner, C. D., Granger, C. B., et al. (2010). Double-dose versus standard-dose clopidogrel and high-dose versus low-dose aspirin in individuals undergoing percutaneous coronary intervention for acute coronary syndromes (CURRENT-OASIS 7): a randomised factorial trial. Lancet, 376, 1233–1243.PubMedCrossRef

11.

Saraff, K. Y., Steinhubl, S. R., Hsu, A. P., & Topol, E. J. (2006). Smoking influences the effectiveness of dual antiplatelet therapy on long-term outcomes following percutaneous coronary intervention [Abstract]. Journal of the American College of Cardiology, 47, p36B.

12.

Ferreiro JL, Bhatt D, Ueno M, Bauer D, Angiolillo DJ (2013) Impact of smoking on long-term outcomes in patients with atherosclerotic vascular disease treated with aspirin or clopidogrel: insights from the Clopidogrel versus Aspirin in Patients at Risk of Ischemic Events (CAPRIE) Trial. Journal of the American College of Cardiology. doi:10.1016/j.jacc.2013.10.043.

13.

Salek, F. S. (2010). Relationship between clopidogrel and cigarette smoking status in patients with acute coronary syndromes without ST-segment elevation myocardial infarction [Abstract]. Pharmacotherapy, 30, 154e.

14.

Hochholzer, W., Trenk, D., Mega, J. L., Morath, T., Stratz, C., Valina, C. M., et al. (2011). Impact of smoking on antiplatelet effect of clopidogrel and prasugrel after loading dose and on maintenance therapy. American Heart Journal, 162, 518–526.PubMedCrossRef

15.

Bliden, K. P., Dichiara, J., Lawal, L., Singla, A., Antonino, M. J., Baker, B. A., et al. (2008). The association of cigarette smoking with enhanced platelet inhibition by clopidogrel. Journal of the American College of Cardiology, 52, 531–533.PubMedCrossRef

16.

Ueno, M., Ferreiro, J. L., Desai, B., Tomasello, S. D., Tello-Montoliu, A., Capodanno, D., et al. (2012). Cigarette smoking is associated with a dose–response effect in clopidogrel-treated patients with diabetes mellitus and coronary artery disease: results of a pharmacodynamic study. JACC. Cardiovascular Interventions, 5, 293–300.PubMedCrossRef

17.

Gurbel, P. A., Bliden, K. P., Logan, D. K., Kereiakes, D. J., Lasseter, K. C., White, A., et al. (2013). The influence of smoking status on the pharmacokinetics and pharmacodynamics of clopidogrel and prasugrel: the PARADOX Study. Journal of the American College of Cardiology, 62, 505–512.PubMedCrossRef

18.

Gremmel, T., Steiner, S., Seidinger, D., Koppensteiner, R., Panzer, S., & Kopp, C. W. (2009). Smoking promotes clopidogrel-mediated platelet inhibition in patients receiving dual antiplatelet therapy. Thrombosis Research, 124, 588–591.PubMedCrossRef

19.

Faber, M. S., & Fuhr, U. (2004). Time response of cytochrome P450 1A2 activity on cessation of heavy smoking. Clinical Pharmacology and Therapeutics, 76, 178–184.PubMedCrossRef

20.

Washio, I., Maeda, M., Sugiura, C., Shiga, R., Yoshida, M., Nonen, S., et al. (2011). Cigarette smoke extract induces CYP2B6 through constitutive androstane receptor in hepatocytes. Drug Metabolism and Disposition, 39, 1–3.PubMedCrossRef

21.

Shanker, G., Kontos, J. L., Eckman, D. M., Wesley-Farrington, D., & Sane, D. C. (2006). Nicotine upregulates the expression of P2Y12 on vascular cells and megakaryoblasts. Journal of Thrombosis and Thrombolysis, 22, 213–220.PubMedCrossRef

22.

Jantzen, H. M., Gousset, L., Bhaskar, V., Vincent, D., Tai, A., Reynolds, E. E., et al. (1999). Evidence for two distinct G-protein-couples ADP receptors mediating platelet activation. Thrombosis and Haemostasis, 81, 111–117.PubMed

23.

Lancaster, G. A., Dodd, S., & Williamson, P. R. (2004). Design and analysis of pilot studies: recommendations for good practice. Journal of Evaluation in Clinical Practice, 10, 307–312.PubMedCrossRef

24.

Park, K. W., Kang, S. H., Kang, J., Jeon, K. H., Park, J. J., Han, J. K., et al. (2012). Enhanced clopidogrel response in smokers is reversed after discontinuation as assessed by VerifyNow assay: additional evidence for the concept of ‘smokers' paradox’. Heart, 98, 1000–1006.PubMedCrossRef

25.

Mozaffarian, D., Wilson, P. W., & Kannel, W. B. (2008). Beyond established and novel risk factors: lifestyle risk factors for cardiovascular disease. Circulation, 117, 3031–3038.PubMedCrossRef

26.

Newby, D. E., McLeod, A. L., Uren, N. G., Flint, L., Ludlam, C. A., Webb, D. J., et al. (2001). Impaired coronary tissue plasminogen activator release is associated with coronary atherosclerosis and cigarette smoking: direct link between endothelial dysfunction and atherothrombosis. Circulation, 103, 1936–1941.PubMedCrossRef

27.

Cimmino, G., & Golino, P. (2013). Platelet biology and receptor pathways. Journal of Cardiovascular Translational Research, 6, 299–309.PubMedCrossRef

28.

Angiolillo, D. J., Ueno, M., & Goto, S. (2010). Basic principles of platelet biology and clinical implications. Circulation Journal, 74, 597–607.PubMedCrossRef

29.

Wiviott, S. D., Braunwald, E., McCabe, C. H., Montalescot, G., Ruzyllo, W., Gottlieb, S., et al. (2007). Prasugrel versus clopidogrel in patients with acute coronary syndromes. The New England Journal of Medicine, 357, 2001–2015.PubMedCrossRef

30.

Wallentin, L., Becker, R. C., Budaj, A., Cannon, C. P., Emanuelsson, H., Held, C., et al. (2009). Ticagrelor versus clopidogrel in patients with acute coronary syndromes. The New England Journal of Medicine, 361, 1045–1057.PubMedCrossRef

31.

Wennmalm, A., Benthin, G., Granström, E. F., Persson, L., Petersson, A. S., & Winell, S. (1991). Relation between tobacco use and urinary excretion of thromboxane A2 and prostacyclin metabolites in young men. Circulation, 83, 1698–1704.PubMedCrossRef

32.

Pamukcu, B., Oflaz, H., Onur, I., Cimen, A., & Nisanci, Y. (2011). Effects of cigarette smoking on platelet aggregation. Clinical and Applied Thrombosis/Hemostasis, 17, E175–E180.PubMedCrossRef

33.

Loke WM, Lam Mok Sing K, Lee CY, Chong WL, Chew SE, Huang H, Looi WF, Quek AM, Lim EC, Seet RC (2012) Cyclooxygenase-1-mediated platelet reactivity in young male smokers. Clinical and Applied Thrombosis/Hemostasis. doi:1076029612466284/1076029612466284.

34.

Henry, P., Vermillet, A., Boval, B., Guyetand, C., Petroni, T., Dillinger, J. G., et al. (2011). 24-h time-dependent aspirin efficacy in patients with stable coronary artery disease. Thrombosis and Haemostasis, 105, 336–344.PubMedCrossRef

35.

Haberstock-Debic, H., Andre, P., Mills, S., Phillips, D. R., & Conley, P. B. (2011). A clopidogrel-insensitive inducible pool of P2Y12 receptors contributes to thrombus formation: inhibition by elinogrel, a direct-acting, reversible P2Y12 antagonist. Journal of Pharmacology and Experimental Therapeutics, 339, 54–61.PubMedCrossRef

36.

Mundell, S. J., Barton, J. F., Mayo-Martin, M. B., Hardy, A. R., & Poole, A. W. (2008). Rapid resensitization of purinergic receptor function in human platelets. Journal of Thrombosis and Haemostasis, 6, 1393–1404.PubMedCrossRef

37.

Kanamarlapudi, V., Owen, S. E., Saha, K., Pope, R. J., & Mundell, S. J. (2012). ARF6-dependent regulation of P2Y receptor traffic and function in human platelets. PLoS One, 7(8), e43532.PubMedCentralPubMedCrossRef

38.

Roe, M. T., Armstrong, P. W., Fox, K. A., White, H. D., Prabhakaran, D., Goodman, S. G., et al. (2012). Prasugrel versus clopidogrel for acute coronary syndromes without revascularization. The New England Journal of Medicine, 367, 1297–1309.PubMedCrossRef

39.

Cornel, J. H., Ohman, M., Neely, B., Clemmensen, P., Sritara, P., Zamoryakhin, D., et al. (2013). Impact of smoking status on clinical outcomes with prasugrel versus clopidogrel in patients with acute coronary syndromes managed without revascularization: Insights from the TRILOGY ACS trial [Abstract]. Journal of the American College of Cardiology, 61, E159.CrossRef

Title: Impact of Cigarette Smoking on P2Y12 Receptor Binding Activity Before and After Clopidogrel Therapy in Patients with Coronary Artery Disease
Authors: 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
Publication date: 01-02-2014
Publisher: Springer US
Published in: Journal of Cardiovascular Translational Research / Issue 1/2014
Print ISSN: 1937-5387
Electronic ISSN: 1937-5395
DOI: https://doi.org/10.1007/s12265-013-9530-8

Keynote webinar | Spotlight on medication adherence

Springer Medicine

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

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

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