Effect of genetic variations on ticagrelor plasma levels and clinical outcomes

European Heart Journal

Volumn 36, Issue 29, 2015, Pages 1901-1912a

  Varenhorst, Christoph ^a   Eriksson, Niclas ^a   Johansson, Åsa ^a   Barratt, Bryan J ^b   Hagström, Emil ^a   Åkerblom, Axel ^a   Syvänen, Ann Christine ^a   Becker, Richard C ^c,d   James, Stefan K ^a   Katus, Hugo A ^e   Husted, Steen ^f   Steg, Ph Gabriel ^g,h,i,j   Siegbahn, Agneta ^a   Voora, Deepak ^k   Teng, Renli ^b   Storey, Robert F ^l   Wallentin, Lars ^a  

^a UPPSALA UNIVERSITY   (Sweden)

^b ASTRAZENECA   (United Kingdom)

^c UNIVERSITY OF CINCINNATI ACADEMIC HEALTH CENTER   (United States)

^d UNIVERSITY OF CINCINNATI   (United States)

^e UNIVERSITY HOSPITAL HEIDELBERG   (Germany)

^f REGIONAL HOSPITAL WEST JUTLAND   (Denmark)

^g INSERM   (France)

^h BICHAT HOSPITAL   (France)

ⁱ UniversitCrossed D Sign Paris CitCrossed D Sign   (France)

^j ROYAL BROMPTON HOSPITAL   (United Kingdom)

^k DUKE CLINICAL RESEARCH INSTITUTE   (United States)

^l UNIVERSITY OF SHEFFIELD   (United Kingdom)

more..

Author keywords

Acute Coronary Syndrome; Antiplatelet Treatment; Clopidogrel; Genome wide association study; Pharmacogenetics; Ticagrelor

Indexed keywords

AR C 124910XX; CYTOCHROME P450 3A4; DRUG METABOLITE; GENOMIC DNA; GLUCURONOSYLTRANSFERASE 2B7; SOLUTE CARRIER ORGANIC ANION TRANSPORTER 1B1; TICAGRELOR; UNCLASSIFIED DRUG; ADENOSINE; AR C124910XX; CYP3A4 PROTEIN, HUMAN; CYTOCHROME P450 3A; GLUCURONOSYLTRANSFERASE; ORGANIC ANION TRANSPORTER; PURINERGIC P2Y RECEPTOR ANTAGONIST; SLCO1B1 PROTEIN, HUMAN; UGT2B7 PROTEIN, HUMAN;

ACUTE CORONARY SYNDROME; ADULT; AGED; AREA UNDER THE CURVE; ARTICLE; DNA EXTRACTION; DRUG BLOOD LEVEL; FEMALE; GENE LINKAGE DISEQUILIBRIUM; GENE LOCUS; GENE REPLICATION; GENETIC ASSOCIATION; GENETIC VARIABILITY; GENOTYPING TECHNIQUE; HUMAN; MAJOR CLINICAL STUDY; MALE; OUTCOME ASSESSMENT; PHARMACOGENETICS; PRIORITY JOURNAL; SINGLE NUCLEOTIDE POLYMORPHISM; ANALOGS AND DERIVATIVES; BLOOD; CLINICAL TRIAL; COMPARATIVE STUDY; CONTROLLED STUDY; GENETICS; GENOME-WIDE ASSOCIATION STUDY; GENOTYPE; METABOLISM; MIDDLE AGED; MULTICENTER STUDY; PHASE 3 CLINICAL TRIAL; RANDOMIZED CONTROLLED TRIAL; TREATMENT OUTCOME;

ACUTE CORONARY SYNDROME; ADENOSINE; ADULT; CYTOCHROME P-450 CYP3A; FEMALE; GENOME-WIDE ASSOCIATION STUDY; GENOTYPE; GLUCURONOSYLTRANSFERASE; HUMANS; MALE; MIDDLE AGED; ORGANIC ANION TRANSPORTERS; POLYMORPHISM, SINGLE NUCLEOTIDE; PURINERGIC P2Y RECEPTOR ANTAGONISTS; TREATMENT OUTCOME;

EID: 84939497736     PISSN: 0195668X     EISSN: 15229645     Source Type: Journal    
DOI: 10.1093/eurheartj/ehv116     Document Type: Article

References (25)

1. Wallentin L, Becker RC, Budaj A, Cannon CP, Emanuelsson H, Held C, Horrow J, Husted S, James S, Katus H, Mahaffey KW, Scirica BM, Skene A, Steg PG, Storey RF, Harrington RA, Freij A, Thorsén M. Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med 2009;361:1045-1057.
2. Husted S, van Giezen JJJ. Ticagrelor: the first reversibly binding oral P2Y12 receptor antagonist. Cardiovasc Ther 2009;27:259-274.
3. VAN Giezen JJJ, Nilsson L, Berntsson P, Wissing B-M, Giordanetto F, Tomlinson W, Greasley PJ. Ticagrelor binds to human P2Y(12) independently fromADP but antagonizes ADP-induced receptor signaling and platelet aggregation. J Thromb Haemost 2009;7:1556-1565.
4. Wallentin L, James S, Storey RF, Armstrong M, Barratt BJ, Horrow J, Husted S, Katus H, Steg PG, Shah SH, Becker RC. Effect of CYP2C19 and ABCB1 single nucleotide polymorphisms on outcomes of treatment with ticagrelor versus clopidogrel for acute coronary syndromes: a genetic substudy of the PLATO trial. Lancet 2010; 376:1320-1328.
5. Teng R, Oliver S, Hayes MA, Butler K. Absorption, distribution, metabolism, and excretion of ticagrelor in healthy subjects. Drug Metab Dispos 2010;38:1514-1521.
6. Zhou D, Andersson TB, GrimmSW. In vitro evaluation of potential drug-drug interactions with ticagrelor: cytochrome P450 reaction phenotyping, inhibition, induction, and differential kinetics. Drug Metab Dispos 2011;39:703-710.
7. Husted S, Emanuelsson H, Heptinstall S, Sandset PM, Wickens M, Peters G. Pharmacodynamics, pharmacokinetics, and safety of the oral reversible P2Y12 antagonist AZD6140 with aspirin in patients with atherosclerosis: a double-blind comparison to clopidogrel with aspirin. Eur Heart J 2006;27:1038-1047.
8. AstraZeneca Ticagrelor (Brilinta). Full prescribing information. http://www1. astrazeneca-us.com/pi/brilinta.pdf (10 April 2014).
9. AstraZeneca Ticagrelor (Brilique). Summary of product characteristics. Version 9, 03/2013. http://www.ema.europa.eu/docs/en-GB/document-library/EPAR-Product-Information/human/001241/WC500100494.pdf (10 April 2014).
10. James S, Akerblom A, Cannon CP, Emanuelsson H, Husted S, Katus H, Skene A, Steg PG, Storey RF, Harrington R, Becker R,Wallentin L. Comparison of ticagrelor, the first reversible oral P2Y12 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: 599-605.
11. Gunderson KL, Steemers FJ, Lee G, Mendoza LG, Chee MS.Agenome-wide scalable SNP genotyping assay using microarray technology. Nat Genet 2005;37:549-554.
12. Steemers FJ, ChangW, Lee G, Barker DL, Shen R, Gunderson KL. Whole-genome genotyping with the single-base extension assay. Nat Methods 2006;3:31-33.
13. Sillén H,Cook M, Davis P. Determination of ticagrelor and two metabolites in plasma samples by liquid chromatography and mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci 2010;878:2299-2306.
14. Price AL, Patterson NJ, Plenge RM, Weinblatt ME, Shadick NA, Reich D. Principal components analysis corrects for stratification in genome-wide association studies. Nat Genet 2006;38:904-909.
15. Aulchenko YS, Ripke S, Isaacs A, van Duijn CM. GenABEL: an R library for genomewide association analysis. Bioinformatics 2007;23:1294-1296.
16. Aulchenko YS, Struchalin MV, van Duijn CM. ProbABEL package for genome-wide association analysis of imputed data. BMC Bioinformatics 2010;11:134.
17. Teng R. Pharmacokinetic, pharmacodynamic and pharmacogenetic profile of the oral antiplatelet agent ticagrelor. Clin Pharmacokinet 2012;51:305-318.
18. Storey RF, Husted S, Harrington RA, Heptinstall S, Wilcox RG, Peters G, WickensM, Emanuelsson H, Gurbel P,Grande P, Cannon CP. Inhibition of platelet aggregation by AZD6140, a reversible oral P2Y12 receptor antagonist, compared with clopidogrel in patientswith acute coronary syndromes. J AmColl Cardiol 2007; 50:1852-1856.
19. Teng R, Butler K. Pharmacokinetics, pharmacodynamics, tolerability and safety of single ascending doses of ticagrelor, a reversibly binding oral P2Y12 receptor antagonist, in healthy subjects. Eur J Clin Pharmacol 2010;66:487-496.
20. Varenhorst C, James S, Erlinge D, Brandt JT, BraunOO,Man M, SiegbahnA,Walker J, Wallentin L, Winters KJ, Close SL. 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: 1744-1752.
21. Mega JL, Simon T, Collet J-P, Anderson JL, Antman EM, Bliden K, Cannon CP, Danchin N, Giusti B, Gurbel P, Horne BD, Hulot J-S, Kastrati A, Montalescot G, Neumann F-J, 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.
22. Mega JL, Close SL, Wiviott SD, Shen L,Walker JR, SimonT, Antman EM, Braunwald E, Sabatine MS. 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.
23. Link E, Parish S, Armitage J, Bowman L, Heath S, Matsuda F, Gut I, Lathrop M, Collins R. SLCO1B1 variants and statin-induced myopathy-a genomewide study. N Engl J Med 2008;359:789-799.
24. Voora D, Shah SH, Spasojevic I, Ali S, Reed CR, Salisbury BA, Ginsburg GS. The SLCO1B1 5 genetic variant is associated with statin-induced side effects. J Am Coll Cardiol 2009;54:1609-1616.
25. Ramsey LB, Bruun GH, Yang W, Trevinõ LR, Vattathil S, Scheet P, Cheng C, Rosner GL, Giacomini KM, Fan Y, Sparreboom A, Mikkelsen TS, Corydon TJ, Pui C-H, Evans WE, Relling MV. Rare versus common variants in pharmacogenetics: SLCO1B1 variation and methotrexate disposition. Genome Res 2012; 22:1-8.