Cytochrome P-450 polymorphisms and response to clopidogrel

New England Journal of Medicine

Volumn 360, Issue 4, 2009, Pages 354-362

  Mega, Jessica L ^a   Close, Sandra L ^b   Wiviott, Stephen D ^a   Shen, Lei ^b   Hockett, Richard D ^b   Brandt, John T ^b   Walker, Joseph R ^c   Antman, Elliott M ^a   Macias, William ^b   Braunwald, Eugene ^a   Sabatine, Marc S ^a  

^a BRIGHAM AND WOMEN S HOSPITAL   (United States)

^b ELI LILLY AND COMPANY   (United States)

^c DAIICHI SANKYO INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CLOPIDOGREL; CYTOCHROME P450 2C19; PRASUGREL;

ACUTE CORONARY SYNDROME; ADULT; AGED; ALLELE; ARTICLE; CARDIOVASCULAR EFFECT; CLINICAL TRIAL; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; DRUG BLOOD LEVEL; DRUG EFFICACY; DRUG SAFETY; FEMALE; GENETIC VARIABILITY; HEART INFARCTION; HUMAN; HUMAN EXPERIMENT; LOADING DRUG DOSE; MAJOR CLINICAL STUDY; MALE; NORMAL HUMAN; PERCUTANEOUS CORONARY INTERVENTION; PRIORITY JOURNAL; PROTEIN POLYMORPHISM; STENT THROMBOSIS; STROKE; THROMBOCYTE AGGREGATION; THROMBOCYTE DYSFUNCTION; THROMBOSIS;

EID: 58749094444     PISSN: 00284793     EISSN: 15334406     Source Type: Journal    
DOI: 10.1056/NEJMoa0809171     Document Type: Article

References (35)

1. The Clopidogrel in Unstable Angina to Prevent Recurrent Ischemic Events Trial Investigators. 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. [Errata, N Engl J Med 2001;345:1506, 1716.]
2. Sabatine MS, Cannon CP, Gibson CM, et al. Addition of clopidogrel to aspirin and fibrinolytic therapy for myocardial infarction with ST-segment elevation. N Engl J Med 2005;352:1179-89.
3. King SB III, Smith SC Jr, Hirshfeld JW Jr, et al. 2007 Focused update of the ACC/AHA/SCAI 2005 guideline update for percutaneous coronary intervention: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines: 2007 Writing Group to Review New Evidence and Update the ACC/AHA/SCAI 2005 Guideline Update for Percutaneous Coronary Intervention. Circulation 2008;117:261-95. [Erratum, Circulation 2008;117(6):e161.]
4. 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.
5. O'Donoghue M, Wiviott SD. Clopidogrel response variability and future therapies: clopidogrel: does one size fit all? Circulation 2006;114(22):e600- e606.
6. Angiolillo DJ, Fernandez-Ortiz A, Bernardo E, et al. Variability in individual responsiveness to clopidogrel: clinical implications, management, and future perspectives. J Am Coll Cardiol 2007;49:1505-16.
7. Matetzky S, Shenkman B, Guetta V, et al. Clopidogrel resistance is associated with increased risk of recurrent atherothrombotic events in patients with acute myocardial infarction. Circulation 2004;109:3171-5.
8. Hochholzer W, Trenk D, Bestehorn HP, et al. Impact of the degree of peri-interventional platelet inhibition after loading with clopidogrel on early clinical outcome of elective coronary stent placement. J Am Coll Cardiol 2006;48:1742-50.
9. Gurbel PA, Bliden KP, Samara W, et al. Clopidogrel effect on platelet reactivity in patients with stent thrombosis: results of the CREST Study. J Am Coll Cardiol 2005;46:1827-32.
10. Trenk D, Hochholzer W, Fromm MF, et al. Cytochrome P450 2C19 681G>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.
11. Kurihara A, Hagihara K, Kazui M, Ishizuka T, Farid NA, Ikeda T. In vitro metabolism of antiplatelet agent clopidogrel: cytochrome P450 isoforms responsible for two oxidation steps involved in the active metabolite formation. Drug Metab Rev 2005;37:Suppl 2:99. abstract.
12. Rehmel JL, Eckstein JA, Farid NA, et al. Interactions of two major metabolites of prasugrel, a thienopyridine antiplatelet agent, with the cytochromes P450. Drug Metab Dispos 2006;34:600-7.
13. Ingelman-Sundberg M, Sim SC, Gomez A, Rodriguez-Antona C. Influence of cytochrome P450 polymorphisms on drug therapies: pharmacogenetic, pharmacoepigenetic and clinical aspects. Pharmacol Ther 2007;116:496-526.
14. Farid NA, Payne CD, Small DS, et al. Cytochrome P450 3A inhibition by ketoconazole affects prasugrel and clopidogrel pharmacokinetics and pharmacodynamics differently. Clin Pharmacol Ther 2007;81:735-41.
15. Brandt JT, Close SL, Iturria SJ, et al. Common polymorphisms of CYP2C19 and CYP2C9 affect the pharmacokinetic and pharmacodynamic response to clopidogrel but not prasugrel. J Thromb Haemost 2007;5:2429-36.
16. Kim KA, Park PW, Hong SJ, Park JY. The effect of CYP2C19 polymorphism on the pharmacokinetics and pharmacodynamics of clopidogrel: a possible mechanism for clopidogrel resistance. Clin Pharmacol Ther 2008;84:236-42.
17. Payne CD, Li YG, Small DS, et al. Increased active metabolite formation explains the greater platelet inhibition with prasugrel compared to high-dose clopidogrel. J Cardiovasc Pharmacol 2007;50:555-62.
18. Small DS, Payne CD, Kothare PA, et al. Comparison of pharmacokinetics and pharmacodynamics of prasugrel and clopidogrel loading doses in healthy Chinese and Caucasian subjects. Clin Pharmacol Ther 2008;83:Suppl 1:S56. abstract.
19. Payne CD, Li YG, Brandt JT, et al. Switching directly to prasugrel from clopidogrel results in greater inhibition of platelet aggregation in aspirin-treated subjects. Platelets 2008;19:275-81.
20. Small DS, Farid NA, Li YG, et al. Effect of ranitidine on the pharmacokinetics and pharmacodynamics of prasugrel and clopidogrel. Curr Med Res Opin 2008;24:2251-7.
21. Farid NA, Small DS, Payne CD, et al. Effect of atorvastatin on the pharmacokinetics and pharmacodynamics of prasugrel and clopidogrel in healthy subjects. Pharmacotherapy 2008;28:1483-94.
22. Li YG, Ni L, Small D, et al. Inhibition of platelet aggregation with prasugrel and clopidogrel. Am J Cardiol 2008;102:Suppl:76i.
23. Farid NA, McIntosh M, Garofolo F, et al. Determination of the active and inactive metabolites of prasugrel in human plasma by liquid chromatography/ tandem mass spectrometry. Rapid Commun Mass Spectrom 2007;21:169-79.
24. Wiviott SD, Antman EM, Gibson CM, et al. Evaluation of prasugrel compared with clopidogrel in patients with acute coronary syndromes: design and rationale for the TRial to assess Improvement in Therapeutic Outcomes by optimizing platelet InhibitioN with prasugrel Thrombolysis In Myocardial Infarction 38 (TRITON-TIMI 38). Am Heart J 2006;152:627-35.
25. Wiviott SD, Braunwald E, McCabe CH, et al. Prasugrel versus clopidogrel in patients with acute coronary syndromes. N Engl J Med 2007;357:2001-15.
26. Wiviott SD, Braunwald E, McCabe CH, et al. Intensive oral antiplatelet therapy for reduction of ischaemic events including stent thrombosis in patients with acute coronary syndromes treated with percutaneous coronary intervention and stenting in the TRITON-TIMI 38 trial: a sub-analysis of a randomised trial. Lancet 2008;371:1353-63.
27. Daly TM, Dumaual CM, Miao X, et al. Multiplex assay for comprehensive genotyping of genes involved in drug metabolism, excretion, and transport. Clin Chem 2007;53:1222-30.
28. Dumaual C, Miao X, Daly TM, et al. Comprehensive assessment of metabolic enzyme and transporter genes using the Affymetrix Targeted Genotyping System. Pharmacogenomics 2007;8:293-305.
29. Special report: genotyping for cytochrome P450 polymorphisms to determine drug-metabolizer status: TEC assessment. Chicago: Blue Cross Blue Shield Technology Evaluation Center Assessment Program, 2004.
30. Karolinska Institute. Human Cytochrome P450 (CYP) Allele Nomenclature Committee home page. (Accessed December 29, 2008, at http://www.cypalleles.ki. se.)
31. Desta Z, Zhao X, Shin JG, Flockhart DA. Clinical significance of the cytochrome P450 2C19 genetic polymorphism. Clin Pharmacokinet 2002;41:913-58.
32. de Morais SM, Wilkinson GR, Blaisdell J, Nakamura K, Meyer UA, Goldstein JA. The major genetic defect responsible for the polymorphism of S-mephenytoin metabolism in humans. J Biol Chem 1994;269:15419-22.
33. Hulot JS, Bura A, Villard E, et al. Cytochrome P450 2C19 loss-of-function polymorphism is a major determinant of clopidogrel responsiveness in healthy subjects. Blood 2006;108:2244-7.
34. Angiolillo DJ, Fernandez-Ortiz A, Bernardo E, et al. Contribution of gene sequence variations of the hepatic cytochrome P450 3A4 enzyme to variability in individual responsiveness to clopidogrel. Arterioscler Thromb Vasc Biol 2006;26:1895-900.
35. Suh JW, Koo BK, Zhang SY, et al. Increased risk of atherothrombotic events associated with cytochrome P450 3A5 polymorphism in patients taking clopidogrel. CMAJ 2006;174:1715-22. [Erratum, CMAJ 2006;175:64.]