Combination of clopidogrel and proton pump inhibitors: Implications for clinicians

Journal of Cardiovascular Pharmacology and Therapeutics

Volumn 15, Issue 4, 2010, Pages 326-337

  Tran, Marie ^a   Tafreshi, Javad ^a   Pai, Ramdas G ^b  

^a LOMA LINDA UNIVERSITY MEDICAL CENTER   (United States)

^b LOMA LINDA UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

acute myocardial infarction; antithrombotic; cardiac pharmacology; thrombosis

Indexed keywords

CLOPIDOGREL; ESOMEPRAZOLE; LANSOPRAZOLE; OMEPRAZOLE; PANTOPRAZOLE; PROTON PUMP INHIBITOR; RABEPRAZOLE; ANTITHROMBOCYTIC AGENT; CYP2C19 PROTEIN, HUMAN; CYTOCHROME P450; DRUG DERIVATIVE; TICLOPIDINE; UNSPECIFIC MONOOXYGENASE;

ANTICOAGULANT THERAPY; DRUG COST; DRUG METABOLISM; DRUG SAFETY; DRUG USE; FOOD AND DRUG ADMINISTRATION; GASTROINTESTINAL SYMPTOM; HEART INFARCTION; HUMAN; MEDLINE; PRIORITY JOURNAL; PROSPECTIVE STUDY; REVIEW; RISK ASSESSMENT; TRANSIENT ISCHEMIC ATTACK; UNSTABLE ANGINA PECTORIS; CARDIOVASCULAR DISEASE; CHEMICALLY INDUCED DISORDER; CLINICAL TRIAL (TOPIC); DRUG COMBINATION; DRUG INTERACTION; GENETICS; METABOLISM; MORTALITY; RISK FACTOR; STROKE; TREATMENT OUTCOME;

ARYL HYDROCARBON HYDROXYLASES; CARDIOVASCULAR DISEASES; CLINICAL TRIALS AS TOPIC; CYTOCHROME P-450 ENZYME SYSTEM; DRUG INTERACTIONS; DRUG THERAPY, COMBINATION; HUMANS; MYOCARDIAL INFARCTION; OMEPRAZOLE; PLATELET AGGREGATION INHIBITORS; PROTON PUMP INHIBITORS; RISK FACTORS; STROKE; TICLOPIDINE; TREATMENT OUTCOME;

EID: 78651314123     PISSN: 10742484     EISSN: 19404034     Source Type: Journal    
DOI: 10.1177/1074248410369109     Document Type: Review

References (69)

1. World Health Organization. World Health Statistics 2008. http://www.who.int/whosis/whostat/EN-WHS08-Part1.pdf. Accessed July 24, 2009.
2. Schafer JA, Kjesbo NK, Gleason PP Critical review of prasugrel for formulary decision makers. J Manag Care Pharm. 2009 ; 15 (4). 335-343.
3. Smith SC Jr, Feldman TE, Hirshfeld JW Jr, et al. 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 (ACC/ AHA/SCAI Writing Committee to Update 2001 Guidelines for Percutaneous Coronary Intervention). Circulation. 2006 ; 113 (7). e166 - e286.
4. 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 (18). 1502-1517.
5. The Ubiquitous Roles of Cytochrome450 Proteins. Metal Ions in Life Sciences. Vol 3. Wiley ; 2007.
6. Danielson PB The cytochrome P450 superfamily: biochemistry, evolution and drug metabolism in humans. Curr Drug Metab. 2002 ; 3 (6). 561-597.
7. Guengerich FP Cytochrome p450 and chemical toxicology. Chem Res Toxicol. 2008 ; 21 (1). 70-83.
8. Savi P., Pereillo JM, Uzabiaga MF, et al. Identification and biological activity of the active metabolite of clopidogrel. Thromb Haemost. 2000 ; 84 (5). 891-896.
9. Savi P., Herbert JM, Pflieger AM, et al. Importance of hepatic metabolism in the antiaggregating activity of the thienopyridine clopidogrel. Biochem Pharmacol. 1992 ; 44 (3). 527-532.
10. Gilard M., Arnaud B., Cornily JC, et al. Influence of omeprazole on the antiplatelet action of clopidogrel associated with aspirin: the randomized, double-blind OCLA (Omeprazole Clopidogrel Aspirin) study. J Am Coll Cardiol. 2008 ; 51 (3). 256-260.
11. Barragan P., Bouvier JL, Roquebert PO, et al. Resistance to thienopyridines: clinical detection of coronary stent thrombosis by monitoring of vasodilator-stimulated phosphoprotein phosphorylation. Cathether Cardiovasc Interv. 2003 ; 59 (3). 295-302.
12. 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 (4). 475-484.
13. Li XQ, Andersson TB, Ahlstrom M., Weidolf L. 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 (8). 821-827.
14. Aubert Re, Epstein RS, Teagarden JR, et al. Abstract 3998: Proton pump inhibitors effect on clopidogrel effectiveness: the Clopidogrel Medco Outcomes Study. Circulation. 2008 ; 118: S815.
15. Medco Press Announcement. http://www.medcoresearch.com/community/cardio/ clopidogrel. Accessed August 24, 2009.
16. Nelson D. Cytochrome P. 450 Homepage. University of Tennessee. http://drnelson.utmem.edu/CytochromeP450.html. Accessed September 02, 2009.
17. US Food and Drug Administration. Cardiovascular and Renal Drug Advisory Committee Briefing Document on Prasugrel for ACS. February 3, 2009. http://www.fda/gov/ohrms/dockets/ac/09/briefing/2009-4412b1-01-FDA.pdf. Accessed July 28, 2009.
18. Sugidachi A., Ogawa T., Hasegawa M., et al. Active metabolites of CS-747 (Prasugrel, LY640315) and clopidogrel show similar in vitro P2Y12 receptor blockade but great in vivo potency of CS-747 [abstract]. J Thromb Haemost. 2005 ; 3 (suppl 1). P1109.
19. Sugidachi A., Asai F., Ogawa T., Inoue T., Koike H. The in vivo pharmacological profile of CS-747, a novel antiplatelet agent with platelet ADP receptor antagonist properties. Br J Pharmacol. 2000 ; 129 (7). 1439-1446.
20. Herbert JM, Frehel D., Vallee E., et al. Clopidogrel, a novel antiplatelet and antithrombotic agent. Cardiovasc Drug Rev. 1993 ; 11 (2). 180-198.
21. Caplain H., Donat F., Gaud C., Necciari J. Pharmacokinetics of clopidogrel. Semin Thromb Hemost. 1999 ; 25 (suppl 2). 25-28.
22. Kurihara A., Hagihara K., Kazui M., Ishizuka T., Farid NA, Ikeda T. In vivo metabolism of antiplatelet agent clopidogrel: cytochrome P450 isoforms responsible for two oxidation steps involved in active metabolite formation. Drug Dev Rev. 2005 ; 37 (suppl 2). 99.
23. 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 (1). 53-59.
24. 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 (5). 735-741.
25. Fontana P., Hulot JS, De Moerloose P., Gaussem P. Influence of CYP2C19 and CYP3A4 gene polymorphisms on clopidogrel responsiveness in healthy subjects. J Thromb Haemost. 2007 ; 5 (10). 2153-2155.
26. 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 (1). 92-99. http://dmd.aspetjournals.org. Accessed February 2, 2010.
27. 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 (7). 2244-2247.
28. Umemura K., Furtura T., Kondo K. The common gene variants of CYP2C19 affect pharmacokinetics and pharmacodynamics in an active metabolite of clopidogrel in healthy subjects. J Thromb Haemost. 2008 ; 6 (8). 1439-1441.
29. Mega JL, Close SL, Wiviott SD, et al. Cytochrome P-450 polymorphisms and response to clopidogrel. N Engl J Med. 2009 ; 360 (4). 354-362.
30. Williams ET, Jones KO, Ponsler GD, et al. The biotransformation of prasugrel, a new thienopyridine prodrug, by the human carboxylesterases 1 and 2. Drug Metab Dispos. 2008 ; 36 (7). 1227-1232.
31. Wallentin L. P2Y12 inhibitors: differences in properties and mechanisms of action and potential consequences for clinical use. Eur Heart J. 2009; 30 (16). 1964-1977.
32. 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 (12). 2429-2436.
33. Mega JL, Close SL, Wiviott SD, et al. Cytochrome p450 genetic polymorphisms and the response to prasugrel: relationship to pharmacokinetic, pharmacodynamic, and clinical outcomes. Circulation. 2009 ; 119 (19). 2553-2560.
34. 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 (25). 3171-3175.
35. Furuta T., Sugimoto M., Shirai N., Ishizaki T. CYP2C19 pharmacogenomics associated with theraphy of Helicobacter pylori infection and gastroesophageal reflux diseases with a proton pump inhibitor. Pharmacogenomics. 2007 ; 8 (9). 1199-1210.
36. 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 (9). 1742-1750.
37. 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 (10). 1827-1832.
38. Roche VF The chemically elegant proton pump inhibitors. Am J Pharm Educ. 2006 ; 70 (5). 101.
39. Wiviott SD, Braunwald E., McCabe CH, et al. Prasugrel versus clopigogrel in patients with acute coronary syndromes. N Eng J Med. 2007 ; 357 (20). 2001-2015.
40. Wiviott SD, Trenk D., Frelinger AL, et al. Prasugrel compared with high loading-and maintenance-dose clopidogrel in patients with planned percutaneous coronary intervention: the prasugrel in comparison to clopidogrel for inhibition of platelet activation and aggregation-thrombolysis in myocardial infarction 44 trial. Circulation. 2007 ; 116 (25). 2923-2932.
41. 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 (9). 937-944.
42. Juurlink D., Gomes T., Ko D., et al. A population-based study of the drug interaction between proton pump inhibitors and clopidogrel. CMAJ. 2009 ; 180 (7). 713-718.
43. Society of Cardiovascular Angiography and Interventions. SCAI Statement on "A National Study of the Effect of Individual Proton Pump Inhibitors on Cardiovascular Outcomes in Patients Treated with Clopidogrel Following Coronary Stenting: The Clopidogrel Medco Outcomes Study." www.sci.org/drltl.aspx? PAGE-ID=5870. Accessed July 2009.
44. Sibbing D., Morath T., Stegherr J., et al. Impact of proton pump inhibitors on the antiplatelet effects of clopidogrel. J Thromb Haemost. 2009 ; 101 (4). 714-719.
45. Fock KM, Ang TL, Bee LC, Lee EJ Proton pump inhibitors: do differences in pharmacokinetics translate into differences in clinical outcomes ? Clin Pharmacokinet. 2008 ; 47 (1). 1-6.
46. Howden CW Clinical pharmacology of omeprazole. Clin Pharmacokinet. 1991 ; 20 (1). 38-49.
47. Blume H., Donath F., Warnke A., Schug BS Pharmacokinetic drug interaction profiles of proton pump inhibitors. Drug Saf. 2006 ; 29 (9). 769-784.
48. Khalique SC, Cheng-Lai A. Drug interaction between clopidogrel and proton pump inhibitors. Cardiol Rev. 2009 ; 17 (4). 198-200.
49. Jungnickel PW Pantoprazole: a new proton pump inhibitor. Clin Ther. 2000 ; 22 (11). 1268-1293.
50. Horai Y., Kimura M., Furuie H., et al. Pharmacodynamic effects and kinetic disposition of rabeprazole in relation to CYP2C19 genotypes. Aliment Pharmacol Ther. 2001 ; 15 (6). 793-803.
51. Horn J. Relationship between the metabolism and efficacy of proton pump inhibitors-focus on rabeprazole. Aliment Pharmacol Ther. 2004 ; 20 (suppl 6). 11-19.
52. Lacey VF, Armstrong LL, Goldman MP, Lance LL Lexi-comp Drug Information Handbook. 17 th ed. Ohio, OH: Lexi-Comp Inc ; 2008-2009.
53. Siller-Matula JM, Spiel AO, Lang IM, Kreiner G., Christ G., Jilma B. Effects of pantoprazole and esomeprazole on platelet inhibition by clopidogrel. Am Heart J. 2009 ; 157 (1). 148, e1 - e5.
54. Steinhubl SR, Berger PB, Mann JT III, et al. Early and sustained dual oral antiplatelet therapy following percutaneous coronary intervention: a randomized controlled trial. JAMA. 2002 ; 288 (19). 2411-2420.
55. Dunn SP, Macaulay T., Brennan D., et al. Baseline proton pump inhibitors use is associated with increased cardiovascular events with and without use of clopidogrel in the CREDO trial (abstract 3999). Circulation. 2008 ; 118: S815.
56. Simon T., Verstuyft C., Mary-Krause M., et al. Genetic determinants of response to clopidogrel and cardiovascular events. N Engl Med. 2009 ; 360 (4). 363-375.
57. 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 (9694). 989-997.
58. Cuisset T., Frere C., Quilici J., et al. Comparison of omeprazole and pantoprazole influence on a high 150-mg clopidogrel maintenance dose. J Am Coll Cardiol. 2009 ; 54 (13). 1149-1153.
59. Desta Z., Zhao X., Shin JG, Flockhart DA Clinical significance of the cytochrome P450 2C19 genetic polymorphism. Clin Pharmacokinet. 2002 ; 41 (12). 913-958.
60. Brandt JT, Kirkwood S., Mukopadhay N. CYP2C19*2 polymorphism contributes to a diminished pharmacodynamic response to clopidogrel. J Am Coll Cardiol. 2006 ; 47 (suppl 1). 380A.
61. Frere C., Cuisset T., Gaborit B., Alessi MC, Hulot JS The CYP2C19*17 allele is associated with better platelet response to clopidogrel in patients admitted for non-ST acute coronary syndrome. J Thromb Haemost. 2009 ; 7 (8). 1409-1411.
62. Varenhorst C., James S., Erlinge D., Brandt JT, Braun OO, Man M. Genetic variation of CYP2C19 affects both pharmacokinetic and pharmacodynamic responses to clopidogrel but not prasugrel in aspirin-treated patients with coronary artery disease. Eur Heart J. 2009 ; 30 (14). 1744-1752.
63. Top ten global products - 2007. IMS Midas Monthly. London (UK): IMS Health Inc ; December 2007. www.imshealth.com/deployedfiles/imshealth/Global/ Content/StaticFile/Top-Line-Data/Top10GlobalProducts.pdf. Accessed July 25, 2009.
64. Taha AS, McCloskey C., Prasad R., Bezlyak V. Famotidine for the prevention of peptic ulcers and oesophagitis in patients taking low-dose aspirin (FAMOUS): a phase III, randomized, double-blind, placebo-controlled trial. Lancet. 2009 ; 374 (9684). 119-125.
65. US National Institutes of Health. Clinical Trial Search for Clopidogrel. http://www./clinicaltrials/gov/ct2/show/NCT00950339?term=clopidgrel+and+PPI& rank=3. Accessed March 10, 2010.
66. James S., Akerblom A., Cannon CP, et al. Comparison of ticagrelor, the first reversible oral P2Y(12) receptor antagonist, with clopidogrel in patients with acute coronary syndromes: Rationale, design, and baseline characteristics of the PLATelet inhibition and patient Outcomes (PLATO) trial. Am Heart J. 2009 ; 157 (4). 599-605.
67. Ng FH, Wong SY, Lam KF, et al. Gastrointestinal bleeding in patients receiving a combination of aspirin, clopidogrel, and enoxaparin in acute coronary syndrome. Am J Gastroenterol. 2008 ; 103 (4). 865-871.
68. Bliden KP, DiChiara J., Lawal L., et al. Association of cigarette smoking with enhanced platelet inhibition by clopidogrel. J Am Coll Cardiol. 2008 ; 52 (7). 531-533.
69. Allen M., McLean-Veysey P. Pantoprazole not proven to be different from other PPIs. On-line letter CMAJ. Feb 25, 2009.