Unraveling the pharmacogenetics of clopidogrel: The paraoxonase-1 controversy

Circulation: Cardiovascular Interventions

Volumn 4, Issue 5, 2011, Pages 401-404

  Snoep, Jaapjan D ^a  

^a LEIDEN UNIVERSITY MEDICAL CENTER   (Netherlands)

Author keywords

Acute coronary syndrome; Clopidogrel; Editorials; Pharmacogenetics; Platelet aggregation

Indexed keywords

ARYLDIALKYLPHOSPHATASE 1; CLOPIDOGREL; CYTOCHROME P450 2C19; LOW DENSITY LIPOPROTEIN;

ACUTE CORONARY SYNDROME; GENETIC POLYMORPHISM; GENOTYPE; HEART INFARCTION; HUMAN; LOADING DRUG DOSE; LOSS OF FUNCTION MUTATION; PHARMACOGENETICS; PRIORITY JOURNAL; REVIEW; STENT THROMBOSIS; THROMBOCYTE ACTIVATION;

ARYL HYDROCARBON HYDROXYLASES; FEMALE; HUMANS; MALE; MYOCARDIAL INFARCTION; PLATELET AGGREGATION INHIBITORS; TICLOPIDINE;

EID: 82955229582     PISSN: 19417640     EISSN: 19417632     Source Type: Journal    
DOI: 10.1161/CIRCINTERVENTIONS.111.964668     Document Type: Review

References (15)

1. Snoep JD, Hovens MMC, Eikenboom JCJ, van der Bom JG, Jukema JW, Huisman MV. Clopidogrel nonresponsiveness in patients undergoing percutaneous coronary intervention with stenting: a systematic review and meta-analysis. Am Heart J. 2007;154:221-231. (Pubitemid 47069129)
2. Breet NJ, Van Werkum JW, Bouman HJ, Kelder JC, Ruven HJ, Bal ET, Deneer VH, Harmsze AM, van der Heyden JA, Rensing BJ, Suttorp MJ, Hackeng CM, Ten Berg JM. Comparison of platelet function tests in predicting clinical outcome in patients undergoing coronary stent implantation. JAMA. 2010;303:754-762.
3. Taubert D, Kastrati A, Harlfinger S, Gorchakova O, Lazar A, von BN, Schomig A, Schomig E. Pharmacokinetics of clopidogrel after administration of a high loading dose. Thromb Haemost. 2004;92:311-316. (Pubitemid 39172312)
4. Mega JL, Close SL, Wiviott SD, Shen L, Hockett RD, Brandt JT, Walker JR, Antman EM, Macias W, Braunwald E, Sabatine MS. Cytochrome P-450 polymorphisms and response to clopidogrel. N Engl J Med. 2009; 360:354-362.
5. Shuldiner AR, O'Connell JR, Bliden KP, Gandhi A, Ryan K, Horenstein RB, Damcott CM, Pakyz R, Tantry US, Gibson Q, Pollin TI, Post W, Parsa A, Mitchell BD, Faraday N, Herzog W, Gurbel PA. Association of cytochrome P450 2C19 genotype with the antiplatelet effect and clinical efficacy of clopidogrel therapy. JAMA. 2009;302:849-857.
6. Mega JL, Simon T, Collet JP, Anderson JL, Antman EM, Bliden K, Cannon CP, Danchin N, Giusti B, Gurbel P, Horne BD, Hulot JS, Kastrati A, Montalescot G, Neumann FJ, Shen L, Sibbing D, Steg PG, Trenk D, Wiviott SD, Sabatine MS. Reduced-function CYP2C19 genotype and risk of adverse clinical outcomes among patients treated with clopidogrel predominantly for PCI: a meta-analysis. JAMA. 2010;304:1821-1830.
7. Bauer T, Bouman HJ, Van Werkum JW, Ford NF, Ten Berg JM, Taubert D. Impact of CYP2C19 variant genotypes on clinical efficacy of antiplatelet treatment with clopidogrel: systematic review and meta-analysis. BMJ. 2011;343:d4588.
8. Hochholzer W, Trenk D, Fromm MF, Valina CM, Stratz C, Bestehorn HP, Buttner HJ, Neumann FJ. Impact of cytochrome P450 2C19 loss-offunction polymorphism and of major demographic characteristics on residual platelet function after loading and maintenance treatment with clopidogrel in patients undergoing elective coronary stent placement. J Am Coll Cardiol. 2010;55:2427-2434.
9. Bouman HJ, Schomig E, Van Werkum JW, Velder J, Hackeng CM, Hirschhauser C, Waldmann C, Schmalz HG, Ten Berg JM, Taubert D. Paraoxonase-1 is a major determinant of clopidogrel efficacy. Nat Med. 2011;17:110-116.
10. Sibbing D, Koch W, Massberg S, Byrne RA, Mehilli J, Schulz S, Mayer K, Bernlochner I, Schomig A, Kastrati A. No association of paraoxonase-1 Q192R genotypes with platelet response to clopidogrel and risk of stent thrombosis after coronary stenting. Eur Heart J. 2011; 32:1605-1613.
11. Fontana P, James R, Barazer I, Berdague P, Schved JF, Rebsamen M, Vuilleumier N, Reny JL. Relationship between paraoxonase-1 activity, its Q192R genetic variant and clopidogrel responsiveness in the ADRIE study. J Thromb Haemost. 2011;9:1664-1666.
12. Trenk D, Hochholzer W, Fromm MF, Zolk O, Valina CM, Stratz C, Neumann FJ. Paraoxonase-1 Q192R polymorphism and antiplatelet effects of clopidogrel in patients undergoing elective coronary stent placement. Circ Cardiovasc Genet. 2011;4:429-436.
13. Rideg O, Komócsi A, Magyarlaki T, Tökés-Füzesi M, Miseta A, Kovács GL, Aradi D. Impact of genetic variants on post-clopidogrel platelet reactivity in patients after elective percutaneous coronary intervention [published online ahead of print August 1, 2011]. Pharmacogenomics. doi: 10.2217/pgs.11.73.
14. Hulot JS, Collet JP, Cayla G, Silvain J, Allanic F, Bellemain-Appaix A, Scott ST, Montalescot G. CYP2C19 but not PON1 genetic variants influence clopidogrel pharmacokinetics, pharmacodynamics and clinical efficacy in post-myocardial infarction patients. Circ Cardiovasc Interv. 2011;4:422-428.
15. Bonello L, Tantry US, Marcucci R, Blindt R, Angiolillo DJ, Becker R, Bhatt DL, Cattaneo M, Collet JP, Cuisset T, Gachet C, Montalescot G, Jennings LK, Kereiakes D, Sibbing D, Trenk D, Van Werkum JW, Paganelli F, Price MJ, Waksman R, Gurbel PA. Consensus and future directions on the definition of high on-treatment platelet reactivity to adenosine diphosphate. J Am Coll Cardiol. 2010;56:919-933.