Cigarette Smoking and Clopidogrel Interaction

  • Kristopher J. Swiger
  • Omair Yousuf
  • Kevin P. Bliden
  • Udaya S. Tantry
  • Paul A. Gurbel
Ischemic Heart Disease (D Mukherjee, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Ischemic Heart Disease


Dual antiplatelet therapy (DAPT) with aspirin and an adenosine diphosphate receptor antagonist is central to the modern management of acute coronary syndromes and percutaneous revascularization. The most widely used adenosine diphosphate receptor antagonist, clopidogrel therapy is limited by inter-individual variability in platelet inhibition. Recent data suggest a potential role of smoking in the metabolism of clopidogrel and high on-treatment platelet reactivity. Pharmacodynamic studies and post-hoc analyses of large clinical trials support a link between smoking status and the efficacy of clopidogrel therapy. The mechanism of the interaction between smoking status and clopidogrel efficacy remains unclear but may be mediated by cytochrome P450 (CYP)1A2. There is less evidence available on the influence of smoking status on platelet reactivity and clinical outcomes during prasugrel and ticagrelor therapy.


Clopidogrel Dual antiplatelet therapy Acute coronary syndrome Tobacco use Smoking Percutaneous revascularization Adenosine diphosphate receptor antagonist Prasugrel Ticagrelor High on-treatment platelet reactivity Percutaneous coronary intervention 


Conflict of Interest

K.J. Swiger declares that he has no conflict of interest.

O. Yousuf declares that he has no conflict of interest.

U. Tantry has received support for travel to meetings for the study or other purposes from DCRI. He has also received travel/accommodations/meeting expenses unrelated to activities listed from Accumetrics.

P.A. Gurbel has received support for travel to meetings for the study or other purposes from DCRI. He has been a consultant for Daiichi Sankyo, Lilly, Boehringer Ingleheim, Merck, Medtronic, Iverson Genetics, Pozen, Novartis, Bayer, Astrazeneca, Accumetrics, Nanosphere, Sanofi Aventis, CSL, Hemonetics. He has received grant support from NIH, Daiichi Sankyo/Lilly, Pozen, CSL, Astra Zeneca, Sanofi Aventis, Haemoscope, HCRI, DCRI. He has also received payment for development of educational presentations from Schering Plough, Discovery Channel, Primed and has stock/stock options in Merck, Pfizer, Medtronic.


Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    Ferreiro J, Bhatt D, Ueno M. Differential effect of smoking on long-term outcomes in patients with atherosclerotic vascular disease treated with aspirin or clopidogrel: insights from the Clopidogrel vs Aspirin in Patients at Risk of Ischemic Events Trial [Abstract]. J Am Coll Cardiol. 2012;59:A62.CrossRefGoogle Scholar
  2. 2.
    Yusuf S, Zhao F, Mehta SR, Chrolavicius S, Tognoni G, Fox KK. Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation. N Engl J Med. 2001;345:494–502.Google Scholar
  3. 3.
    Gurbel PA, Bliden KP, Hiatt BL, O’Connor CM. Clopidogrel for coronary stenting: response variability, drug resistance, and the effect of pretreatment platelet reactivity. Circulation. 2003;107:2908–13.PubMedCrossRefGoogle Scholar
  4. 4.
    Gurbel PA, Antonino MJ, Tantry US. Recent developments in clopidogrel pharmacology and their relation to clinical outcomes. Expert Opin Drug Metab Toxicol. 2009;5:989–1004.PubMedCrossRefGoogle Scholar
  5. 5.
    Matetzky S, Shenkman B, Guetta V, Shechter M, Beinart R, Goldenberg I, et al. Clopidogrel resistance is associated with increased risk of recurrent atherothrombotic events in patients with acute myocardial infarction. Circulation. 2004;109:3171–5.Google Scholar
  6. 6.
    Gurbel PA, Bliden KP, Guyer K, Cho PW, Zaman KA, Kreutz RP, et al. Platelet reactivity in patients and recurrent events post-stenting: results of the PREPARE POST-STENTING Study. J Am Coll Cardiol. 2005;46:1820–6.Google Scholar
  7. 7.
    Bonello L, Tantry US, Marcucci R, Blindt R, Angiolillo DJ, Becker R, et al. Consensus and future directions on the definition of high on-treatment platelet reactivity to adenosine diphosphate. J Am Coll Cardiol. 2010;56:919–33.Google Scholar
  8. 8.
    Buonamici P, Marcucci R, Migliorini A, Gensini GF, Santini A, Paniccia R, et al. Impact of platelet reactivity after clopidogrel administration on drug-eluting stent thrombosis. J Am Coll Cardiol. 2007;49:2312–7.Google Scholar
  9. 9.
    Brar SS, ten Berg J, Marcucci R, Price MJ, Valgimigli M, Kim HS, et al. Impact of platelet reactivity on clinical outcomes after percutaneous coronary intervention. A collaborative meta-analysis of individual participant data. J Am Coll Cardiol. 2011;58:1945–54.Google Scholar
  10. 10.
    Bliden KP, Dichiara J, Lawal L, Singla A, Antonino MJ, Baker BA, et al. The association of cigarette smoking with enhanced platelet inhibition by clopidogrel. J Am Coll Cardiol. 2008;52:531–3.Google Scholar
  11. 11.
    Gremmel T, Steiner S, Seidinger D, Koppensteiner R, Panzer S, Kopp CW. Smoking promotes clopidogrel-mediated platelet inhibition in patients receiving dual antiplatelet therapy. Thromb Res. 2009;124:588–91.Google Scholar
  12. 12.
    Price MJ, Nayak KR, Barker CM, Kandzari DE, Teirstein PS. Predictors of heightened platelet reactivity despite dual-antiplatelet therapy in patients undergoing percutaneous coronary intervention. Am J Cardiol. 2009;103:1339–43.PubMedCrossRefGoogle Scholar
  13. 13.
    Motovska Z, Widimsky P, Petr R, Bilkova D, Marinov I, Simek S, et al. Factors influencing clopidogrel efficacy in patients with stable coronary artery disease undergoing elective percutaneous coronary intervention: statin’s advantage and the smoking “paradox”. J Cardiovasc Pharmacol. 2009;53:368–72.Google Scholar
  14. 14.
    Bellemain-Appaix A, Montalescot G, Silvain J, Barthélémy O, Beygui F, Collet JP, et al. Slow response to clopidogrel predicts low response. J Am Coll Cardiol. 2010;55:815–22.Google Scholar
  15. 15.
    Jeong YH, Cho JH, Kang MK, Koh JS, Kim IS, Park Y, et al. Smoking at least 10 cigarettes per day increases platelet inhibition by clopidogrel in patients with ST-segment-elevation myocardial infarction. Thromb Res. 2010;126:e334–8.Google Scholar
  16. 16.
    Liu X, Zhou Y, Yang Q. Impact of smoking-cessation on platelet inhibition of clopidogrel in patients undergoing elective coronary drug-eluting stent implantation short term smoking cessation. Heart. 2010;96:(GWICC abstract).Google Scholar
  17. 17.
    Bliden KP, Tantry US, Storey RF, Jeong YH, Gesheff M, Wei C, et al. The effect of ticagrelor vs clopidogrel on high on-treatment platelet reactivity: combined analysis of the ONSET/OFFSET and RESPOND studies. Am Heart J. 2011;162:160–5.Google Scholar
  18. 18.
    Park KW, Park JJ, Jeon KH, Kang SH, Oh IY, Yang HM, et al. Enhanced clopidogrel responsiveness in smokers: smokers’ paradox is dependent on cytochrome P450 CYP1A2 status. Arterioscl Thromb Vasc Biol. 2011;31:665–71.Google Scholar
  19. 19.
    Zanger UM, Turpeinen M, Klein K, Schwab M. Functional pharmacogenetics/genomics of human cytochromes P450 involved in drug biotransformation. Anal Bioanal Chem. 2008;392:1093–108.PubMedCrossRefGoogle Scholar
  20. 20.
    • Gurbel PA, Nolin T. Clopidogrel efficacy and cigarette smoking status. JAMA. 2012;307:2495–6. This view point examines clinical data from several large-scale trials that have consistently demonstrated reduced or no clinical efficacy from clopidogrel therapy among nonsmokers.PubMedCrossRefGoogle Scholar
  21. 21.
    Saraff K. Smoking influences the effectiveness of dual antiplatelet therapy on long-term outcomes following PCI. J Am Coll Cardiol. 2006:36B:(Abstract 2920–122).Google Scholar
  22. 22.
    Berger JS, Bhatt DL, Steinhubl SR, Shao M, Steg PG, Montalescot G, et al. Smoking, clopidogrel, and mortality in patients with established cardiovascular disease. Circulation. 2009;120:2337–44.Google Scholar
  23. 23.
    Desai NR, Mega JL, Jiang S, Cannon CP, Sabatine MS. Interaction between cigarette smoking and clinical benefit of clopidogrel. J Am Coll Cardiol. 2009;53:1273–8.PubMedCrossRefGoogle Scholar
  24. 24.
    Addad F, Dridi Z, Jemmali M, Mzoughi K, Hassine M, Ghrissi I, et al. [“Smoker’s paradox” and reperfusion’s strategy in acute myocardial infarction]. Ann Cardiol Angéiol. 2010;59:183–9.Google Scholar
  25. 25.
    Salek F. Relationship between clopidogrel and cigarette smoking status in patients with acute coronary syndromes without ST- segment elevation myocardial infarction. Abstract 8. Pharmacotherapy. 2010;30:154e.Google Scholar
  26. 26.
    Mehta SR, Tanguay JF, Eikelboom JW, Jolly SS, Joyner CD, Granger CB, et al. 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. 2010;376:1233–43.Google Scholar
  27. 27.
    Wakabayashi K, Romaguera R, Laynez-Carnicero A, Maluenda G, Ben-Dor I, Sardi G, et al. Impact of smoking on acute phase outcomes of myocardial infarction. Coron Artery Dis. 2011;22:217–22.Google Scholar
  28. 28.
    Hochholzer W, Trenk D, Mega JL, Morath T, Stratz C, Valina CM, et al. Impact of smoking on antiplatelet effect of clopidogrel and prasugrel after loading dose and on maintenance therapy. Am Heart J. 2011;162:518–26.e5.Google Scholar
  29. 29.
    Weisz G, Cox DA, Garcia E, Tcheng JE, Griffin JJ, Guagliumi G, et al. Impact of smoking status on outcomes of primary coronary intervention for acute myocardial infarction—the smoker’s paradox revisited. Am Heart J. 2005;150:358–64.Google Scholar
  30. 30.
    Levine PH. An acute effect of cigarette smoking on platelet function. A possible link between smoking and arterial thrombosis. Circulation. 1973;48:619–23.PubMedCrossRefGoogle Scholar
  31. 31.
    Hung J, Lam JY, Lacoste L, Letchacovski G. Cigarette smoking acutely increases platelet thrombus formation in patients with coronary artery disease taking aspirin. Circulation. 1995;92:2432–6.PubMedCrossRefGoogle Scholar
  32. 32.
    Newby DE, Wright RA, Labinjoh C, Ludlam CA, Fox KA, Boon NA, et al. Endothelial dysfunction, impaired endogenous fibrinolysis, and cigarette smoking: a mechanism for arterial thrombosis and myocardial infarction. Circulation. 1999;99:1411–5.Google Scholar
  33. 33.
    Weinblatt E, Shapiro S, Frank CW, Sager RV. Prognosis of men after first myocardial infarction: mortality and first recurrence in relation to selected parameters. Am J Pub Health Nation’s Health. 1968;58:1329–47.CrossRefGoogle Scholar
  34. 34.
    Helmers C. Short and long-term prognostic indices in acute myocardial infarction. A study of 606 patients initially treated in a coronary care unit. Acta Med Scand. Suppl 1973;555:7–26.PubMedGoogle Scholar
  35. 35.
    Kelly TL, Gilpin E, Ahnve S, Henning H, Ross J. Smoking status at the time of acute myocardial infarction and subsequent prognosis. Am Heart J. 1985;110:535–41.PubMedCrossRefGoogle Scholar
  36. 36.
    Cohen DJ, Doucet M, Cutlip DE, Ho KK, Popma JJ, Kuntz RE. Impact of smoking on clinical and angiographic restenosis after percutaneous coronary intervention: another smoker’s paradox? Circulation. 2001;104:773–8.Google Scholar
  37. 37.
    Hasdai D, Garratt KN, Grill DE, Lerman A, Holmes DR. Effect of smoking status on the long-term outcome after successful percutaneous coronary revascularization. N Engl J Med. 1997;336:755–61.PubMedCrossRefGoogle Scholar
  38. 38.
    Barbash GI, White HD, Modan M, Diaz R, Hampton JR, Heikkila J, et al. Acute myocardial infarction in the young—the role of smoking. The Investigators of the International Tissue Plasminogen Activator/Streptokinase Mortality Trial. Eur Heart J. 1995;16:313–6.Google Scholar
  39. 39.
    Aune E, Røislien J, Mathisen M, Thelle DS, Otterstad JE. The “smoker’s paradox” in patients with acute coronary syndrome: a systematic review. BMC Med. 2011;9:97.PubMedCrossRefGoogle Scholar
  40. 40.
    Shanker G, Kontos JL, Eckman DM, Wesley-Farrington D, Sane DC. Nicotine upregulates the expression of P2Y12 on vascular cells and megakaryoblasts. J Thromb Thrombolysis. 2006;22:213–20.PubMedCrossRefGoogle Scholar
  41. 41.
    Fusegawa Y, Handa S. Platelet aggregation induced by ADP or epinephrine is enhanced in habitual smokers. Thromb Res. 2000;97:287–95.PubMedCrossRefGoogle Scholar
  42. 42.
    Angiolillo DJ, Ferreiro JL. Platelet adenosine diphosphate P2Y12 receptor antagonism: benefits and limitations of current treatment strategies and future directions. Rev Esp Cardiol. 2010;63:60–76.PubMedCrossRefGoogle Scholar
  43. 43.
    Brandt JT, Close SL, Iturria SJ, Payne CD, Farid NA, Ernest CS 2nd, et al. Common polymorphisms of CYP2C19 and CYP2C9 affect the pharmacokinetic and pharmacodynamic response to clopidogrel but not prasugrel. J Thromb Haemost JTH. 2007;5:2429–36.Google Scholar
  44. 44.
    Yousuf O, Bhatt DL. The evolution of antiplatelet therapy in cardiovascular disease. Nat Rev Cardiol. 2011;8:547–59.PubMedCrossRefGoogle Scholar
  45. 45.
    Cadroy Y, Bossavy JP, Thalamas C, Sagnard L, Sakariassen K, Boneu B. Early potent antithrombotic effect with combined aspirin and a loading dose of clopidogrel on experimental arterial thrombogenesis in humans. Circulation. 2000;101:2823–8.Google Scholar
  46. 46.
    Moshfegh K, Redondo M, Julmy F, Wuillemin WA, Gebauer MU, Haeberli A, et al. Antiplatelet effects of clopidogrel compared with aspirin after myocardial infarction: enhanced inhibitory effects of combination therapy. J Am Coll Cardiol. 2000;36:699–705.Google Scholar
  47. 47.
    Gawaz M, Seyfarth M, Muller I, Rudiger S, Pogatsa-Murray G, Wolf B, et al. Comparison of effects of clopidogrel versus ticlopidine on platelet function in patients undergoing coronary stent placement. Am J Cardiol. 2001;87:332–6. A9.Google Scholar
  48. 48.
    Aleil B, Léon C, Cazenave J-P, Gachet C. CYP2C19*2 polymorphism is not the sole determinant of the response to clopidogrel: implications for its monitoring. J Thromb Haemost JTH. 2009;7:1747–9.CrossRefGoogle Scholar
  49. 49.
    Lau WC, Gurbel PA, Watkins PB, Neer CJ, Hopp AS, Carville DG, et al. Contribution of hepatic cytochrome P450 3A4 metabolic activity to the phenomenon of clopidogrel resistance. Circulation. 2004;109:166–71.Google Scholar
  50. 50.
    Clarke TA, Waskell LA. The metabolism of clopidogrel is catalyzed by human cytochrome P450 3A and is inhibited by atorvastatin. Drug Metab Dispos. 2003;31:53–9.PubMedCrossRefGoogle Scholar
  51. 51.
    Mega JL, Close SL, Wiviott SD, Shen L, Hockett RD, Brandt JT, et al. Cytochrome p-450 polymorphisms and response to clopidogrel. N Engl J Med. 2009;360:354–62.Google Scholar
  52. 52.
    Shuldiner A, O’Connell J. Association of cytochrome P450 2C19 genotype with the antiplatelet effect and clinical efficacy of clopidogrel therapy. JAMA. 2009;302:849–57.PubMedCrossRefGoogle Scholar
  53. 53.
    Hulot JS, Bura A, Villard E, Azizi M, Remones V, Goyenvalle C, et al. Cytochrome P450 2C19 loss-of-function polymorphism is a major determinant of clopidogrel responsiveness in healthy subjects. Blood. 2006;108:2244–7.Google Scholar
  54. 54.
    Trenk D, Hochholzer W, Fromm MF, Chialda LE, Pahl A, Valina CM, et al. Cytochrome P450 2C19 681 G>A polymorphism and high on-clopidogrel platelet reactivity associated with adverse 1-year clinical outcome of elective percutaneous coronary intervention with drug-eluting or bare-metal stents. J Am Coll Cardiol. 2008;51:1925–34.Google Scholar
  55. 55.
    Collet JP, Hulot JS, Pena A, Villard E, Esteve JB, Silvain J, et al. Cytochrome P450 2C19 polymorphism in young patients treated with clopidogrel after myocardial infarction: a cohort study. Lancet. 2009;373:309–17.Google Scholar
  56. 56.
    Iba MM, Fung J, Pak YW, Thomas PE, Fisher H, Sekowski A, et al. Dose-dependent up-regulation of rat pulmonary, renal, and hepatic cytochrome P-450 (CYP) 1A expression by nicotine feeding. Drug Metab Dispos. 1999;27:977–82.Google Scholar
  57. 57.
    Liu N, Zhang Q, Vakharia D, Dunbar D, Kaminsky LS. Induction of CYP1A by benzo fluoranthene in human hepatocytes: CYP1A1 or CYP1A2? Arch Biochem. 2001;389:130–4.PubMedCrossRefGoogle Scholar
  58. 58.
    Rasmussen BB, Brix TH, Kyvik KO, Brøsen K. The interindividual differences in the 3-demthylation of caffeine alias CYP1A2 is determined by both genetic and environmental factors. Pharmacogenetics. 2002;12:473–8.Google Scholar
  59. 59.
    Zhou S-F, Wang B, Yang L-P, Liu J-P. Structure, function, regulation, and polymorphism and the clinical significance of human cytochrome P450 1A2. Drug Metab Rev. 2010;42:268–354.PubMedCrossRefGoogle Scholar
  60. 60.
    Ghotbi R, Christensen M, Roh HK, Ingelman-Sundberg M, Aklillu E, Bertilsson L. Comparisons of CYP1A2 genetic polymorphisms, enzyme activity, and the genotype-phenotype relationship in Swedes and Koreans. Eur J Clin Pharmacol. 2007;63:537–46.Google Scholar
  61. 61.
    Sachse C, Brockmöller J, Bauer S, Roots I. Functional significance of a C–>A polymorphism in intron 1 of the cytochrome P450 CYP1A2 gene tested with caffeine. Br J Clin Pharmacol. 1999;47:445–9.PubMedCrossRefGoogle Scholar
  62. 62.
    Yousef A-M, Arafat T, Bulatova NR, Al-Zumyli R. Smoking behavior modulates pharmacokinetics of orally administered clopidogrel. J Clin Pharmacol Ther. 2008;33:439–49.CrossRefGoogle Scholar
  63. 63.
    Miyoshi M, Mizuno M. Comparison of proton pump inhibitors, omeprazole vs rabeprazole, in dual therapy for Helicobacter pylori infection in relation to CYP2C19 genetic polymorphism. J Gastroenterol Hepatol. 2001;723–8.Google Scholar
  64. 64.
    Washio I, Maeda M, Sugiura C, Shiga R, Yoshida M, Nonen S, et al. Cigarette smoke extract induces CYP2B6 through constitutive androstane receptor in hepatocytes. Drug Metab Dispos. 2011;39:1–3.Google Scholar
  65. 65.
    Hukkanen J, Väisänen T, Lassila A, Piipari R, Anttila S, Pelkonen O, et al. Regulation of CYP3A5 by glucocorticoids and cigarette smoke in human lung-derived cells. Am Soc Pharmacol Exp Ther. 2003;304:745–52.Google Scholar
  66. 66.
    • Ueno M, Ferreiro JL, Desai B, Tomasello SD, Tello-Montoliu A, Capodanno D, et al. 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. 2012;5:293–300. This study demonstrated a dose response effect of cigarette smoking on clopidogrel induced platelet inhibition. Higher serum cotinine levels were associated with reduced high on-treatment platelet reactivity in diabetic patients.Google Scholar
  67. 67.
    Cho JH, Jeong YH, Ahn YJ, Kang MK, Koh JS, Kim IS, et al. The impact of smoking on post-clopidogrel platelet reactivity in patients with acute myocardial infarction. Korean Circ J. 2010;40:119–24.Google Scholar
  68. 68.
    Geisler T, Grass D, Bigalke B, Stellos K, Drosch T, Dietz K, et al. The Residual Platelet Aggregation after Deployment of Intracoronary Stent (PREDICT) score. J Thrombd Haemost JTH. 2008;6:54–61.Google Scholar
  69. 69.
    Sibbald M, Yan AT, Huang W, Fox KA, Gore JM, Steg PG, et al. Association between smoking, outcomes, and early clopidogrel use in patients with acute coronary syndrome: insights from the Global Registry of Acute Coronary Events. Am Heart J. 2010;160:855–61.Google Scholar
  70. 70.
    O’Donoghue M, Antman EM, Braunwald E, Murphy SA, Steg PG, Finkelstein A, et al. The efficacy and safety of prasugrel with and without a glycoprotein IIb/IIIa inhibitor in patients with acute coronary syndromes undergoing percutaneous intervention: a TRITON-TIMI 38 (Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition With Prasugrel-Thrombolysis In Myocardial Infarction 38) analysis. J Am Coll Cardiol. 2009;54:678–85.Google Scholar
  71. 71.
    Burling TA, Singleton EG, Bigelow GE, Baile WF, Gottlieb SH. Smoking following myocardial infarction: a critical review of the literature. Heal Psychol. 1984;3:83–96.Google Scholar
  72. 72.
    Faber MS, Fuhr U. Time response of cytochrome P450 1A2 activity on cessation of heavy smoking. Clin Pharmacol Ther. 2004;76:178–84.PubMedCrossRefGoogle Scholar
  73. 73.
    Park KW, Kang SH, Kang J, Jeon KH, Park JJ, Han JK, et al. Enhanced clopidogrel response in smokers is reversed after discontinuation as assessed by VerifyNow assay: additional evidence for the concept of ‘smokers’ paradox’. Heart. 2012;98:1000–6.Google Scholar
  74. 74.
    Mega JL, Close SL, Wiviott SD, Shen L, Walker JR, Simon T, et al. Genetic variants in ABCB1 and CYP2C19 and cardiovascular outcomes after treatment with clopidogrel and prasugrel in the TRITON-TIMI 38 trial: a pharmacogenetic analysis. Lancet. 2010;376:1312–9.Google Scholar
  75. 75.
    •• Gurbel P, Bliden K, Logan D, Al. E. TCT-54 The influence of smoking status on the pharmacodynamics of prasugrel and clopidogrel: the PARADOX Study. J Am Coll Cardiol. 2012;60(17 Suppl): (Abstract). This is the first prospective pharmacodynamic study comparing the effects of clopidogrel vs prasugrel in patients randomized by smoking status. This study may help to explain the results from large scale trials that have demonstrated an attenuated clinical effect of clopidogrel therapy in patients who do not smoke. Google Scholar
  76. 76.
    Cornel JH, Becker RC, Goodman SG, Husted S, Katus H, Santoso A, et al. Prior smoking status, clinical outcomes, and the comparison of ticagrelor with clopidogrel in acute coronary syndromes. Insights from the PLATelet inhibition and patient Outcomes (PLATO) trial. Am Heart J. 2012;164:334–42.e1.Google Scholar
  77. 77.
    Gengo F, Robson M, Rainka M. CYP1A2-inducing medications improve platelet responsiveness to clopidrogrel. J Clini Pharmacol. 2010;50:1069. Abstract 58.Google Scholar
  78. 78.
    Ueno M, Ferreiro J, Dharmashankar K, Tomasselo S. Serum cotinine levels are associated with increased clopidrogrel-induced antiplatelet effects in patients with diabetes mellitus and coronary artery disease. New Orleans: American College of Cardiology (ACC); 2011.Google Scholar
  79. 79.
    Sibbing D, Braun S, Morath T, Mehilli J, Vogt W, Schömig A, et al. Platelet reactivity after clopidogrel treatment assessed with point-of-care analysis and early drug-eluting stent thrombosis. J Am Coll Cardiol. 2009;53:849–56.Google Scholar
  80. 80.
    Anon. A randomized, blinded, trial of clopidogrel vs aspirin in patients at risk of ischemic events (CAPRIE). CAPRIE Steering Committee. Lancet. 1996;348:1329–39.Google Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Kristopher J. Swiger
    • 1
  • Omair Yousuf
    • 1
  • Kevin P. Bliden
    • 2
  • Udaya S. Tantry
    • 3
  • Paul A. Gurbel
    • 3
    • 4
  1. 1.Johns Hopkins University School of MedicineBaltimoreUSA
  2. 2.Sinai Center for Thrombosis ResearchSinai Hospital of BaltimoreBaltimoreUSA
  3. 3.Sinai Center for Thrombosis ResearchSinai Hospital of BaltimoreBaltimoreUSA
  4. 4.Cardiac Catheterization LaboratoryBaltimoreUSA

Personalised recommendations