Prospective Evaluation of On-Clopidogrel Platelet Reactivity Over Time in Patients Treated With Percutaneous Coronary Intervention Relationship With Gene Polymorphisms and Clinical Outcome

被引：293

作者：

Campo, Gianluca ^{[1
,3
]}

Parrinello, Giovanni ^{[4
]}

Ferraresi, Paolo ^{[2
]}

Lunghi, Barbara ^{[2
]}

Tebaldi, Matteo ^{[1
,3
]}

Miccoli, Matteo ^{[1
,3
]}

Marchesini, Jlenia ^{[1
,3
]}

Bernardi, Francesco ^{[4
]}

Ferrari, Roberto ^{[1
,3
]}

Valgimigli, Marco ^{[1
,3
]}

机构：

[1] Azienda Osped Univ St Anna, Cardiovasc Inst, LTTA Ctr, I-44123 Ferrara, Italy

[2] Univ Ferrara, Dept Biochem & Mol Biol, Interdisciplinary Ctr Study Inflammat, I-44100 Ferrara, Italy

[3] Salvatore Maugeri Fdn, Cardiovasc Res Ctr, Ist Ricovero & Cura Carattere Sci, Lumezzane, Italy

[4] Univ Brescia, Med Stat Unit, Brescia, Italy

来源：

JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY | 2011年 / 57卷 / 25期

关键词：

clinical outcome; clopidogrel; gene polymorphism; P2Y12; VerifyNow; platelet reactivity; poor responder; PATIENTS SHOWING RESISTANCE; ASPIRIN AND/OR RESISTANCE; OF-CARE ASSAY; STENT THROMBOSIS; ANTIPLATELET THERAPY; TAILORING TREATMENT; BLEEDING EVENTS; TRIAL; RESPONSIVENESS; AGGREGATION;

D O I：

10.1016/j.jacc.2010.12.047

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Objectives This study sought to investigate the evolving pattern over time of on-clopidogrel platelet reactivity (PR) and its relationship with genotype and clinical outcomes after percutaneous coronary intervention. Background Whether on-clopidogrel PR and role of genotype differ over time is unknown. Methods On-clopidogrel PR before percutaneous coronary intervention, and 1 and 6 months thereafter via VerifyNow P2Y12 (Accumetrics Inc., San Diego, California), CYP2C19*2, *17, CYP3A5*3, and ABCB1 polymorphisms were evaluated in 300 patients. Death, stroke, myocardial infarction, and bleedings were assessed up to 1 year. Results On-clopidogrel PR varied significantly over time, being higher at baseline than at 1 and 6 months after. From baseline to 1 month, 83 of 300 patients varied their response status. This was mainly due to baseline poor responders becoming full responders (75 of 83). Genotype justifies roughly 18% of this trend. CYP2C19*2 and *17 influence on PR was consistent over time, whereas that of ABCB1 appeared of greater impact at baseline. On-clopidogrel PR at 1 month independently best predicts ischemic and bleeding events. We found a therapeutic window (86 to 238 P2Y(12) reactivity units) with a lower incidence of both ischemic and bleeding complications. A risk score was created by combining genotype (ABCB1 and CYP2C19*2), baseline PR, and creatinine clearance to predict 1-month poor responsiveness and 1-year poor prognosis. Conclusions In patients at steady state for clopidogrel undergoing percutaneous coronary intervention, PR decreases from baseline to 1 month. Genotype influences approximate to 18% of this trend. On-clopidogrel PR at 1 month is the strongest predictor of adverse outcomes, and this can be predicted by combining genotype to baseline phenotype and clinical variables. (J Am Coll Cardiol 2011; 57: 2474-83) (C) 2011 by the American College of Cardiology Foundation

引用

页码：2474 / 2483

页数：10

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