CYP2C19genotype-guided antiplatelet therapy: promises and pitfalls

被引：32

作者：

Ellithi, Moataz ^{[1
]}

Baye, Jordan ^{[1
]}

Wilke, Russell A. ^{[1
]}

机构：

[1] Univ South Dakota, Dept Internal Med, Sanford Sch Med, Sioux Falls, SD 57105 USA

来源：

PHARMACOGENOMICS | 2020年 / 21卷 / 12期

基金：

美国国家卫生研究院;

关键词：

clopidogrel; drug-metabolizing enzyme; pharmacogenomics; pharmacokinetics; pleiotropy; polymorphism; Prasugrel; precision medicine; Ticagrelor; PHARMACOGENETICS IMPLEMENTATION CONSORTIUM; PERCUTANEOUS CORONARY INTERVENTION; LOW-DOSE ASPIRIN; CYP2C19; GENOTYPE; CLOPIDOGREL THERAPY; PLATELET REACTIVITY; POLYMORPHISM; GUIDELINES; EVENTS; TRIAL;

D O I：

10.2217/pgs-2020-0046

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Pharmacogenetic variants can alter the mechanism of action (pharmacodynamic gene variants) or kinetic processes such as absorption, distribution, metabolism and elimination (pharmacokinetic gene variants). Many initial successes in precision medicine occurred in the context of genes encoding the cytochromes P450 (CYP enzymes). CYP2C19 activates the antiplatelet drug clopidogrel, and polymorphisms in theCYP2C19gene are known to alter the outcome for patients taking clopidogrel in the context of cardiovascular disease.CYP2C19loss-of-function alleles are specifically associated with increased risk for coronary stent thrombosis and major adverse cardiovascular events in patients taking clopidogrel following percutaneous coronary intervention. We explore successes and challenges encountered as the clinical and scientific communities advanceCYP2C19genotyping in the context of routine patient care.

引用

页码：889 / 897

页数：9

共 60 条

[1]

Amsterdam EA, 2014, J AM COLL CARDIOL, V64, pE139, DOI [10.1016/j.jacc.2014.10.011, 10.1016/j.jacc.2014.09.016, 10.1016/j.jacc.2014.09.017, 10.1161/CIR.0000000000000134]

[2]

Antman EM, 2008, J AM COLL CARDIOL, V51, P2028, DOI [10.1016/j.jacc.2008.04.002, 10.1016/j.jacc.2007.10.001]

[3] Low-dose aspirin in patients with stable cardiovascular disease: A meta-analysis [J].

Berger, Jeffrey S. ;

Brown, David L. ;

Becker, Richard C. .

AMERICAN JOURNAL OF MEDICINE, 2008, 121 (01) :43-49

[4] Double-blind study of the safety of clopidogrel with and without a loading dose in combination with aspirin compared with ticlopidine in combination with aspirin after coronary stenting - The Clopidogrel Aspirin Stent International Cooperative Study (CLASSICS) [J].

Bertrand, ME ;

Rupprecht, HJ ;

Urban, P ;

Gershlick, AH .

CIRCULATION, 2000, 102 (06) :624-629

[5] Long-term Tolerability of Ticagrelor for the Secondary Prevention of Major Adverse Cardiovascular Events A Secondary Analysis of the PEGASUS-TIMI 54 Trial [J].

Bonaca, Marc P. ;

Bhatt, Deepak L. ;

Ophuis, Ton Oude ;

Steg, P. Gabriel ;

Storey, Robert ;

Cohen, Marc ;

Kuder, Julia ;

Im, Kyungah ;

Magnani, Giulia ;

Budaj, Andrzej ;

Theroux, Pierre ;

Hamm, Christian ;

Spinar, Jindrich ;

Kiss, Robert G. ;

Dalby, Anthony J. ;

Medina, Felix A. ;

Kontny, Frederic ;

Aylward, Philip E. ;

Jensen, Eva C. ;

Held, Peter ;

Braunwald, Eugene ;

Sabatine, Marc S. .

JAMA CARDIOLOGY, 2016, 1 (04) :425-432

[6] Effects of Aspirin for Primary Prevention in Persons with Diabetes Mellitus [J].

Bowman, Louise ;

Mafham, Marion ;

Wallendszus, Karl ;

Stevens, Will ;

Buck, Georgina ;

Barton, Jill ;

Murphy, Kevin ;

Aung, Theingi ;

Haynes, Richard ;

Cox, Jolyon ;

Murawska, Aleksandra ;

Young, Allen ;

Lay, Michael ;

Chen, Fang ;

Sammons, Emily ;

Waters, Emma ;

Adler, Amanda ;

Bodansky, Jonathan ;

Farmer, Andrew ;

McPherson, Roger ;

Neil, Andrew ;

Simpson, David ;

Peto, Richard ;

Baigent, Colin ;

Collins, Rory ;

Parish, Sarah ;

Armitage, Jane .

NEW ENGLAND JOURNAL OF MEDICINE, 2018, 379 (16) :1529-1539

[7]

Brandt J T, 2007, J Thromb Haemost, V5, P2429

[8] Multisite Investigation of Outcomes With Implementation of CYP2C19 Genotype-Guided Antiplatelet Therapy After Percutaneous Coronary Intervention [J].

Cavallari, Larisa H. ;

Lee, Craig R. ;

Beitelshees, Amber L. ;

Cooper-DeHoff, Rhonda M. ;

Duarte, Julio D. ;

Voora, Deepak ;

Kimmel, Stephen E. ;

McDonough, Caitrin W. ;

Gong, Yan ;

Dave, Chintan V. ;

Pratt, Victoria M. ;

Alestock, Tameka D. ;

Anderson, R. David ;

Alsip, Jorge ;

Ardati, Amer K. ;

Brott, Brigitta C. ;

Brown, Lawrence ;

Chumnumwat, Supatat ;

Clare-Salzler, Michael J. ;

Coons, James C. ;

Denny, Joshua C. ;

Dillon, Chrisly ;

Elsey, Amanda R. ;

Hamadeh, Issam S. ;

Harada, Shuko ;

Hillegass, William B. ;

Hines, Lindsay ;

Horenstein, Richard B. ;

Howell, Lucius A. ;

Jeng, Linda J. B. ;

Kelemen, Mark D. ;

Lee, Yee Ming ;

Magvanjav, Oyunbileg ;

Montasser, May ;

Nelson, David R. ;

Nutescu, Edith A. ;

Nwaba, Devon C. ;

Pakyz, Ruth E. ;

Palmer, Kathleen ;

Peterson, Josh F. ;

Pollin, Toni I. ;

Quinn, Alison H. ;

Robinson, Shawn W. ;

Schub, Jamie ;

Skaar, Todd C. ;

Smith, D. Max ;

Sriramoju, Vindhya B. ;

Starostik, Petr ;

Stys, Tomasz P. ;

Stevenson, James M. .

JACC-CARDIOVASCULAR INTERVENTIONS, 2018, 11 (02) :181-191

[9] A Genotype-Guided Strategy for Oral P2Y12 Inhibitors in Primary PCI [J].

Claassens, Daniel M. F. ;

Vos, Gerrit J. A. ;

Bergmeijer, Thomas O. ;

Hermanides, Renicus S. ;

van 't Hof, Arnoud W. J. ;

van der Harst, Pim ;

Barbato, Emanuele ;

Morisco, Carmine ;

Gin, Richard M. Tjon Joe ;

Asselbergs, Folkert W. ;

Mosterd, Arend ;

Herrman, Jean-Paul R. ;

Dewilde, Willem J. M. ;

Janssen, Paul W. A. ;

Kelder, Johannes C. ;

Postma, Maarten J. ;

de Boer, Anthonius ;

Boersma, Cornelis ;

Deneer, Vera H. M. ;

ten Berg, Jurrien M. .

NEW ENGLAND JOURNAL OF MEDICINE, 2019, 381 (17) :1621-1631

[10] Mechanisms of disease:: Platelet activation and atherothrombosis [J].

Davi, Giovanni ;

Patrono, Carlo .

NEW ENGLAND JOURNAL OF MEDICINE, 2007, 357 (24) :2482-2494

← 1 2 3 4 5 6 →