Nonresponders to clopidogrel: Pharmacokinetics and interactions involved

Expert Opinion on Pharmacotherapy

Volumn 11, Issue 14, 2010, Pages 2391-2403

  Giorgi, Mariano A ^a,b   Di Girolamo, Guillermo ^c,d   Gonzlez, Claudio D ^b,e  

^a FLENI   (Argentina)

^b UNIVERSIDAD AUSTRAL   (Argentina)

^c UNIVERSIDAD DE BUENOS AIRES   (Argentina)

^d FAVALORO UNIVERSITY   (Argentina)

^e CEMIC   (Argentina)

Author keywords

Clopidogrel; Interactions; Nonresponders; Pharmacogenomic; Pharmacokinetic

Indexed keywords

ACETYLSALICYLIC ACID; ANTITHROMBOCYTIC AGENT; ATORVASTATIN; CERIVASTATIN; CIMETIDINE; CLOPIDOGREL; CLOPIDOGREL PLUS OMEPRAZOLE; CYTOCHROME P450 1A2; CYTOCHROME P450 2B6; CYTOCHROME P450 2C19; CYTOCHROME P450 3A4; CYTOCHROME P450 3A5; ESOMEPRAZOLE; ETRAVIRINE; FELBAMATE; FLUCONAZOLE; FLUINDOSTATIN; FLUOXETINE; FLUVOXAMINE; KETOCONAZOLE; LANSOPRAZOLE; MEVINOLIN; OMEPRAZOLE; PANTOPRAZOLE; PRASUGREL; PRAVASTATIN; PROTON PUMP INHIBITOR; RABEPRAZOLE; SIMVASTATIN; UNCLASSIFIED DRUG; UNINDEXED DRUG;

ACUTE CORONARY SYNDROME; ACUTE HEART INFARCTION; BARE METAL STENT; CLINICAL TRIAL; CORONARY ARTERY DISEASE; DRUG ABSORPTION; DRUG EFFICACY; DRUG ELUTING STENT; DRUG METABOLISM; DRUG RESISTANCE; DRUG RESPONSE; DRUG TRANSFORMATION; FOOD AND DRUG ADMINISTRATION; GASTROINTESTINAL HEMORRHAGE; GENETIC POLYMORPHISM; GENOTYPE; HUMAN; HYPERCHOLESTEROLEMIA; INTESTINE ABSORPTION; ISCHEMIC HEART DISEASE; PERCUTANEOUS CORONARY INTERVENTION; PHARMACOGENOMICS; REVIEW; RISK BENEFIT ANALYSIS; SINGLE NUCLEOTIDE POLYMORPHISM; ST SEGMENT ELEVATION MYOCARDIAL INFARCTION; THROMBOCYTE AGGREGATION; THROMBOCYTE AGGREGATION INHIBITION;

ACUTE CORONARY SYNDROME; BIOTRANSFORMATION; DRUG INTERACTIONS; DRUG RESISTANCE; HUMANS; PLATELET AGGREGATION INHIBITORS; POLYMORPHISM, GENETIC; PROTON PUMP INHIBITORS; TICLOPIDINE;

EID: 77956566371     PISSN: 14656566     EISSN: None     Source Type: Journal    
DOI: 10.1517/14656566.2010.498820     Document Type: Review

References (63)

1. The Clopidogrel in Unstable Angina to Prevent Recurrent 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
2. Mehta SR, Yusuf S, Peters RJ, et al. Effects of pretreatment with clopidogrel and aspirin followed by long-term therapy in patients undergoing percutaneous coronary intervention: the PCI-CURE study. Lancet 2001;358:527-533
3. Sabatine MS, Cannon CP, Gibson CM, et al.; CLARITY-TIMI 28 Investigators. Addition of clopidogrel to aspirin and fibrinolytic therapy for myocardial infarction with ST-segment elevation. N Engl J Med 2005;352:1179-1189
4. Chen ZM, Jiang LX, Chen YP, et al.; COMMIT (Clopidogrel and Metoprolol in Myocardial Infarction Trial) Collaborative Group. Addition of clopidogrel to aspirin in 45,852 patients with acute myocardial infarction: randomized placebo-controlled trial. Lancet 2005;366:1607-1621
5. Jackevicius CA, Tu JV, Demers V, et al. Cardiovascular outcomes after a change in prescription policy for clopidogrel. N Engl J Med 2008;359:1802-1810
6. Smith SC Jr, Feldman TE, Hirshfeld JW Jr, et al. ACC/AHA/SCAI 2005 Guideline update for percutaneous coronary intervention - summary article: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (ACC/AHA/SCAI Writing Committee to Update the 2001 Guidelines for Percutaneous Coronary Intervention). J Am Coll Cardiol 2006;47:216-235
7. Grines CL, Bonow RO, Casey DE, et al. Prevention of premature discontinuation of dual antiplatelet therapy in patients with coronary artery stents: a science advisory from the American Heart Association, American College of Cardiology, Society for Cardiovascular Angiography and Interventions, American College of Surgeons, and American Dental Association, with representation from the American College of Physicians. Circulation 2007;115:813-818
8. 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;109:3171-3175
9. Combescure C, Fontana P, Mallouk N, et al. Clinical implications of clopidogrel non-response in cardiovascular patients: a systematic review and meta-analysis. J Thromb Haemost 2010;8:923-933
10. 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;49:1505-1516
11. Savi P, Pereillo JM, Uzabiaga MF, et al. Identification and biological activity of the active metabolite of clopidogrel. Thromb Haemost 2000;84:891-896
12. Kazui M, Nishiya Y, Ishizuka T, et al. Identification of the human cytochrome P450 enzymes involved in the two oxidative steps in the bioactivation of clopidogrel to its pharmacologically active metabolite. Drug Metab Dispos 2010;38:92-99
13. Roden DM, Stein M. Clopidogrel and the concept of high risk pharmacokinetics. Circulation 2009;119:2127-2130
14. Pereillo JM, Maftouh M, Andrieu A, et al. Structure and stereochemistry of the active metabolite of clopidogrel. Drug Metab Dispos 2002;30:1288-1295
15. Reist M, Roy-De Vos M, Montseny JP, et al. Very slow chiral inversion of clopidogrel in rats: a pharmacokinetic and mechanistic investigation. Drug Metab Dispos 2000;28:1405-1410
16. Di Girolamo G, Czerniuk P, Bertuola R, Keller G. Bioequivalence of two tablet formulations of clopidogrel in healthy Argentinean volunteers: a single dose, randomized-sequence, open label cross over study. Clin Ther 2010;32:161-170
17. International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use. Tripartite Harmonised Guideline. Impurities in New Drug Products Q3B (R2). Current Step 4 version, dated 2 June 2006. Available from: http://www.ich.org/LOB/media/ MEDIA421.pdf [Last accessed 29 January 2010]
18. Gomez Y, Adams E, Hoogmartens J. Analysis of purity in 19 drug product tablets containing clopidogrel: 18 copies versus the original brand. J Pharm Biomed Anal 2004;34:341-348
19. Savi P, Combalbert J, Gaich C, et al. The antiaggregating activity of clopidogrel is due to a metabolic activation by the hepatic cytochrome P450-1A. Thromb Haemost 1994;72:313-317
20. Sofi F, Marcucci R, Gori AM, et al. Clopidogrel non-responsiveness and risk of cardiovascular morbidity. Thromb Haemost 2010;103(4):891-898
21. Wilkinson GR. Drug metabolism and variability among patients in drug response. N Engl J Med 2005;352:2211-2221
22. Xie HG, Kim RB, Wood AJ, et al. Molecular basis of ethnic differences in drug disposition and response. Annu Rev Pharmacol Toxicol 2001;41:815-850
23. Wedlund PJ. The CYP2C19 enzyme polymorphism. Pharmacology 2000;61:174-183
24. 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;108:2244-2247
25. Giusti B, Gori AM, Marcucci R, et al. Cytochrome P450 2C19 loss-of-function polymorphism, but not CYP3A4 IVS10 +12G/A and P2Y12 T744C polymorphisms, is associated with response variability to dual antiplatelet treatment in high-risk vascular patients. Pharmacogenet Genomics 2007;17:1057-1064
26. Shuldiner AR, O'Connel JR, Bliden KP, et al. Association of cytochrome P450 2C19 genotype with the antiplatelet effect and clinical efficacy of clopidogrel therapy. JAMA 2009;302:849-858
27. 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 outcome of elective percutaneous coronary intervention with drug eluting or bare metal stents. J Am Coll Cardiol 2008;51:1925-1934
28. Collet JP, Hulot JS, Pena A, et al. Cytochrome P450 2C19 polymorphism in young patients treated with clopidogrel after myocardial infarction: a cohort study. Lancet 2009;373:309-317
29. Simon T, Verstuyft C, Mary-Krause M, et al. Genetic determinants of response to clopidogrel and cardiovascular events. N Engl J Med 2009;360:363-375
30. Mega JL, Close Sl, Wiviott SD, et al. Cytochrome P-450 polymorphisms and response to clopidogrel. N Engl J Med 2009;360:354-362
31. Wiviott SD, Braunwald E, McCabe C, et al. Prasugrel versus clopidogrel in patients with acute coronary syndromes. N Engl J Med 2007;357:2001-2015 (Pubitemid 350106708)
32. Wrighton SA, Schuetz EG, Thummel KE, et al. The human CYP3A subfamily: practical considerations. Drug Metab Rev 2000;32:339-361
33. Suh JW, Koo BK, Zhang SY, et al. Increased risk of atherothrombotic events associated with cytochrome P450 3A5 polymorphism in patients talking clopidogrel. CMAJ 2006;174:1715-1722
34. Frere C, Cuisset T, Morange PE, et al. Effect of cytochrome P450 polymorphisms on platelet reactivity after treatment with clopidogrel in acute coronary syndrome. Am J Cardiol 2008;101:1088-1093
35. 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;26:1895-1900
36. Ellis KI, Stouffer GA, McLeod HL, et al. Clopidogrel pharmacogenomics and risk of inadequate platelet inhibition: US FDA recommendations. Pharmacogenomics 2009;10:1799-1817
37. Storey RF. Clopidogrel in acute coronary syndrome: to genotype or not? Lancet 2009;373:276-278
38. Bauer LA. Clinical pharmacokinetics and pharmacodynamics concepts. In: Bauer LA, editor, Clinical pharmacokinetcs handbook. McGraw Hill; 2006. p. 3-18
39. Lau WC, Waskell LA, Watkins PB, et al. Atorvastatin reduces the ability of clopidogrel to inhibit platelet aggregation: a new drug-drug interaction. Circulation 2003;107:32-37
40. Saw J, Steinhubl SR, Berger PB, et al. Lack of adverse clopidogrel-atorvastatin clinical interaction from secondary analysis of a randomized placebo-controlled trial. Circulation 2003;108:921-924
41. Hocholzer W, Trenk D, Frundi D, et al. Time dependence of platelet inhibition after 600 mg loading dose of clopidogrel in a large unselected cohort of candidates for percutaneous coronary intervention. Circulation 2005;111:2560-2564
42. Delaney JA, Opatrny L, Brophy JM, et al. Drug-drug interactions between antithrombotic medications and the risk of gastrointestinal bleeding. CMAJ 2007;177:347-351
43. Bhatt DL, Scheiman J, Abraham NS, et al. ACCF/ACG/AHA 2008 expert consensus document on reducing the gastrointestinal risks of antiplatelet therapy and NSAID use: a report of the American College of Cardiology Foundation Task Force on Clinical Expert Consensus Documents. J Am Coll Cardiol 2008;52:1502-1517
44. Ho PM, Maddox TM, Wang L, et al. Risk of adverse outcomes associated with concomitant use of clopidogrel and proton pump inhibitors following acute coronary syndrome. JAMA 2009;301:937-944
45. Li XQ, Andersson TB, Ahlstrom M, et al. Comparison of inhibitory effects of the proton pump-inhibiting drugs omeprazole, esomeprazole, lansoprazole, pantoprazole, and rabeprazole on human cytochrome P450 activities. Drug Metab Dispos 2004;32:821-827
46. Gilard M, Arnaud B, Le Gal G, et al. Influence of omeprazole on the antiplatelet action of clopidogrel associated to aspirin. J Thromb Haemost 2006;4:2508-2509
47. Gilard M, Arnaud B, Cornily JC, et al. Influence of omeprazole on the antiplatelet action of associated with aspirin. The randomized, double-blind, OCLA (omeprazole clopidogrel aspirin) study. J Am Coll Cardiol 2008;51:256-260
48. O'Donoghue ML, Braunwald E, Antman EM, et al. Pharmacodynamic effect and clinical efficacy of clopidogrel and prasugrel with or without a proton-pump inhibitor: an analysis of two randomized trials. Lancet 2009;374:989-997
49. Juurlink DN, Gomes T, Ko DT, et al. A population-based study of the drug interaction between proton-pump inhibitors and clopidogrel. CMAJ 2009;180:713-718
50. Siller-Matula JM, Spiel AO, Lang IM, et al. Effects of pantoprazole and esomeprazole on platelet inhibition by clopidogrel. Am Heart J 2009;157:148.e1-e5
51. Ray WA, Murray KT, Griffin MR, et al. Outcomes with concurrent use of clopidogrel and proton-pump inhibitors: a cohort study. Ann Intern Med 2010;152:393-395
52. European Medicines Agency. Public statement on possible interaction between clopidogrel and proton-pump inhibitors. Available from: http://www.emea.europa.eu/ humandocs/PDFs/EPAR/Plavix/ 32895609en.pdf [Last accessed 22 November 2009]
53. Food and Drug Administration. Public health advisory: updated safety information about a drug interaction between clopidogrel bisulfate (marketed as Plavix) and omeprazole (marketed as Prilosec and Prilosec OTC). Available from: http://www.fda.gov/ Drugs/DrugSafety/PostmarketDrugSafety InformationforPatientsandProviders/ DrugSafetyInformationforHeathcare Professionals/ucm190787 [Last accessed 11 January 2010]
54. Sibbing D, Kastrati A. Risk of combining PPIs with thienopyridines: fact or fiction? Lancet 2009;374:952-954
55. Bahtt DL. COGENT: a prospective, randomized, placebo controlled trial of omeprazole in patients receiving aspirin and clopidogrel. Presented at Transcatheter Cardiovascular Therapeutics, 24 September 2009, San Francisco, California, USA
56. Griswold ME, Localio AR, Mulrw C. Propensity score adjustment with multilevel data: setting your sites on decreasing selection bias. Ann Intern Med 2010;152:337-345
57. Harjai KJ, Shenoy C, Orshaw P, et al. Six-month outcomes with or without proton-pump inhibitors after successful PCI: insights from the Guthrie PCI Registry. J Am Coll Cardiol 2010;55(Suppl 1):, A179.E1675
58. Klungela OH, Martensa EP, Psaty BM, et al. Methods to assess intended effects of drug treatment in observational studies are reviewed. J Clin Epidemiol 2004;57:1223-1231
59. Depta JP, Bhatt DL. Omeprazole and clopidogrel: should clinicians be worried? Cleve Clin J Med 2010;7:113-116
60. Plavix 75 mg label. Available from: http://packageinserts.bms.com/pi/pi- plavix.pdf [Last accessed 21 February 2010]
61. Rehmel JLF, 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;34:600-607
62. Small DS, Farid NA, Payne CD, et al. Effects of the proton pump inhibitor lansoprazole on the pharmacokinetics and pharmacodynamics of prasugrel and clopidogrel. J Clin Pharmacol 2008;48:475-484
63. Wallentin L, Becker RC, Buda A, et al. Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med 2009;361:1045-1057