Cardiovascular risk among patients on clopidogrel anti-platelet therapy after placement of drug-eluting stents is modified by genetic variants in both the CYP2C19 and ABCB1 genes

Thrombosis and Haemostasis

Volumn 109, Issue 4, 2013, Pages 744-754

  Carlquist, John F ^a,b   Knight, Stacey ^a,b   Horne, Benjamin D ^a,b   Huntinghouse, John A ^a   Rollo, Jeffrey S ^a   Muhlestein, J Brent ^a,b   May, Heidi ^a   Anderson, Jeffrey L ^a,b  

^a Intermountain Heart Institute   (United States)

^b UNIVERSITY OF UTAH SCHOOL OF MEDICINE   (United States)

Author keywords

Antiplatelet agents; Cardiovascular risk; Pharmacogenetics

Indexed keywords

ACETYLSALICYLIC ACID; CLOPIDOGREL;

ABCB1 GENE; ADULT; AGED; ALLELE; ARTICLE; CARDIOVASCULAR RISK; CYP2C19 GENE; DISEASE ASSOCIATION; DNA EXTRACTION; DRUG ELUTING STENT; ELECTROCARDIOGRAPHY; FEMALE; GAIN OF FUNCTION MUTATION; GENE; GENETIC VARIABILITY; GENOTYPE; HEART INFARCTION; HUMAN; KAPLAN MEIER METHOD; LOADING DRUG DOSE; MAJOR CLINICAL STUDY; MALE; POLYMERASE CHAIN REACTION; PRIORITY JOURNAL; RISK ASSESSMENT; UNIVARIATE ANALYSIS;

AGED; ARYL HYDROCARBON HYDROXYLASES; CHI-SQUARE DISTRIBUTION; CORONARY THROMBOSIS; DRUG-ELUTING STENTS; FEMALE; GENE FREQUENCY; GENETIC PREDISPOSITION TO DISEASE; HUMANS; MALE; MIDDLE AGED; MYOCARDIAL INFARCTION; P-GLYCOPROTEIN; PERCUTANEOUS CORONARY INTERVENTION; PHARMACOGENETICS; PHENOTYPE; PLATELET AGGREGATION INHIBITORS; POLYMORPHISM, SINGLE NUCLEOTIDE; PROPORTIONAL HAZARDS MODELS; PROSTHESIS DESIGN; RISK ASSESSMENT; RISK FACTORS; TICLOPIDINE; TIME FACTORS; TREATMENT OUTCOME;

EID: 84875924518     PISSN: 03406245     EISSN: None     Source Type: Journal    
DOI: 10.1160/TH12-05-0336     Document Type: Article

References (24)

1. Bonello L, Tantry US, Marcucci 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: 919-933.
2. Hulot JS, Collet JP, Cayla G, et al. 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.
3. Taubert D, von Beckerath N, Grimberg G, et al. Impact of P-glycoprotein on clopidogrel absorption. Clin Pharmacol Ther 2006; 80: 486-501.
4. Simon T, Bhatt DL, Bergougnan L, et al. Genetic polymorphisms and the impact of a higher clopidogrel dose regimen on active metabolite exposure and antiplatelet response in healthy subjects. Clin Pharmacol Ther 2011; 90: 287-295.
5. de Morais SM, Wilkinson GR, Blaisdell J, et al. The major genetic defect responsible for the polymorphism of S-mephenytoin metabolism in humans. J Biol Chem 1994; 269: 15419-15422.
6. 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.
7. Mega JL, Simon T, Collet JP, et al Reduced-function CYP2C19 genotype and risk of adverse clinical outcomes among patients treated with clopidogrel predominantly for PCI: a meta-analysis. J Am Med Assoc 2010; 304: 1821-1830.
8. Giusti B, Gori AM, Marcucci R, et al. Relation of cytochrome P450 2C19 lossof-function polymorphism to occurrence of drug-eluting coronary stent thrombosis. Am J Cardiol 2009; 103: 806-811.
9. Sibbing D, Stegherr J, Latz W, et al. Cytochrome P450 2C19 loss-of-function polymorphism and stent thrombosis following percutaneous coronary intervention. Eur Heart J 2009; 30: 916-922.
10. 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.
11. Sim SC, Risinger C, Dahl ML, et al. A common novel CYP2C19 gene variant causes ultrarapid drug metabolism relevant for the drug response to proton pump inhibitors and antidepressants. Clin Pharmacol Ther 2006; 79: 103-113.
12. 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.
13. Tiroch KA, Sibbing D, Koch W, et al. Protective effect of the CYP2C19 *17 polymorphism with increased activation of clopidogrel on cardiovascular events. Am Heart J 2010; 160: 506-512.
14. Mega JL, Close SL, Wiviott SD, 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: 1312-1319.
15. 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.
16. Paré G, Mehta SR, Yusuf S, et al. Effects of CYP2C19 genotype on outcomes of clopidogrel treatment. N Engl J Med 2010; 363: 1704-1714.
17. 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: 1925-1934.
18. Cutlip DE, Windecker S, Mehran R, et al. Clinical end points in coronary stent trials: a case for standardized definitions. Circulation. 2007; 115: 2344-2351.
19. Tang K, Wong LP, Lee EJ, et al. Genomic evidence for recent positive selection at the human MDR1 gene locus. Hum Mol Genet 2004; 13: 783-797.
20. Siddiqui A, Kerb R, Weale ME, et al. Association of multidrug resistance in epilepsy with a polymorphism in the drug-transporter gene ABCB1. N Engl J Med 2003; 348: 1442-1448.
21. Sibbing D, Gebhard D, Koch W, et al. Isolated and interactive impact of common CYP2C19 genetic variants on the antiplatelet effect of chronic clopidogrel therapy. J Thromb Haemost 2010; 8: 1685-1693.
22. Zabalza M, Subirana I, Sala J, et al. Meta-analyses of the association between cytochrome CYP2C19 loss-and gain-of-function polymorphisms and cardiovascular outcomes in patients with coronary artery disease treated with clopidogrel. Heart 2012; 98: 100-108.
23. Price MJ, Murray SS, Angiolillo DJ, et al. Influence of genetic polymorphisms on the effect of high-and standard-dose clopidogrel after percutaneous coronary intervention: the GIFT (Genotype Information and Functional Testing) study. J Am Coll Cardiol. 2012; 59: 1928-1937.
24. Armero S, Bonello L, Berbis J, et al. Rate of nuisance bleedings and impact on compliance to prasugrel in acute coronary syndromes. Am J Cardiol 2011; 108: 1710-1713.