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J Am Coll Cardiol. 2011 Jun 21;57(25):2474-83. doi: 10.1016/j.jacc.2010.12.047.

Prospective evaluation of on-clopidogrel platelet reactivity over time in patients treated with percutaneous coronary intervention relationship with gene polymorphisms and clinical outcome.

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1
Cardiovascular Institute, Azienda Ospedaliero-Universitaria Sant'Anna, LTTA Center, Ferrara, Italy. cmpglc@unife.it

Abstract

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 P2Y₁₂ 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 ≈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.

PMID:
21679849
DOI:
10.1016/j.jacc.2010.12.047
[Indexed for MEDLINE]
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