The Pharmacogenetics and Pharmacodynamics of Clopidogrel Response An Analysis From the PRINC (Plavix Response in Coronary Intervention) Trial

被引：101

作者：

Gladding, Patrick ^{[1
]}

Webster, Mark ^{[1
]}

Zeng, Irene ^{[1
]}

Farrell, Helen ^{[1
]}

Stewart, Jim ^{[1
]}

Ruygrok, Peter ^{[1
]}

Ormiston, John ^{[1
]}

El-Jack, Seif ^{[1
]}

Armstrong, Guy ^{[1
]}

Kay, Patrick ^{[1
]}

Scott, Douglas ^{[1
]}

Gunes, Arzu ^{[2
]}

Dahl, Marja-Liisa ^{[2
]}

机构：

[1] Auckland City Hosp, Green Lane Cardiovasc Serv, Auckland 1030, New Zealand

[2] Uppsala Univ, Dept Med Sci, Uppsala, Sweden

来源：

JACC-CARDIOVASCULAR INTERVENTIONS | 2008年 / 1卷 / 06期

基金：

瑞典研究理事会;

关键词：

clopidogrel; pharmacogenetics; antiplatelets;

D O I：

10.1016/j.jcin.2008.09.008

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Objectives This study assessed the effect of pharmacogenetics on the antiplatelet effect of clopidogrel. Background Variability in clopidogrel response might be influenced by polymorphisms in genes coding for drug metabolism enzymes (cytochrome P450 [CYP] family), transport proteins (P-glycoprotein) and/or target proteins for the drug (adenosine diphosphate-receptor P2Y12). Methods Sixty patients undergoing elective percutaneous coronary intervention in the randomized PRINC (Plavix Response in Coronary Intervention) trial had platelet function measured using the VerifyNow P2Y12 analyzer after a 600-mg or split 1,200-mg loading dose and after a 75- or 150-mg daily maintenance dosage. Polymerase chain reaction-based genotyping evaluated polymorphisms in the CYP2C19, CYP2C9, CYP3A4, CYP3A5, ABCB1, P2Y12, and CES genes. Results CYP2C19*1*1 carriers had greater platelet inhibition 2 h after a 600-mg dose (median: 23%, range: 0% to 66%), compared with platelet inhibition in CYP2C19*2 or *4 carriers (10%, 0% to 56%, p = 0.029) and CYP2C19*17 carriers (9%, 0% to 98%, p = 0.026). CYP2C19*2 or *4 carriers had greater platelet inhibition with the higher loading dose than with the lower dose at 4 h (37%, 8% to 87% vs. 14%, 0% to 22%, p = 0.002) and responded better with the higher maintenance dose regimen (51%, 15% to 86% vs. 14%, 0% to 67%, p = 0.042). Conclusions Carriers of the CYP2C19*2 and *4 alleles showed reduced platelet inhibition after a clopidogrel 600-mg loading dose but responded to higher loading and maintenance dose regimens. Genotyping for the relevant gene polymorphisms may help to individualize and optimize clopidogrel treatment. (Australia New Zealand Clinical Trials Registry; ACTRN12606000129583) (J Am Coll Cardiol Intv 2008;1:620-7) (C) 2008 by the American College of Cardiology Foundation

引用

页码：620 / 627

页数：8

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