Evaluation of the incremental prognostic value of the combination of CYP2C19 poor metabolizer status and ABCB1 3435 TT polymorphism over conventional risk factors for cardiovascular events after drug-eluting stent implantation in East Asians.
Genet Med
; 18(8): 833-41, 2016 08.
Article
en En
| MEDLINE
| ID: mdl-26699760
ABSTRACT
PURPOSE:
We evaluated the incremental prognostic value of combining the CYP2C19 poor metabolizer (PM) and ABCB1 3435 TT for adverse clinical outcomes over conventional risk factors in a percutaneous coronary intervention (PCI) cohort.METHODS:
We enrolled 2,188 patients. The primary end point was a composite of death from any cause, nonfatal myocardial infarction (MI), and stroke during 1-year follow-up. The population was stratified into the following four groups CYP2C19 EM/IM+ABCB1 3435 CC/CT, CYP2C19 EM/IM+ABCB1 3435 TT, CYP2C19 PM+ABCB1 3435 CC/CT, and CYP2C19 PM+ABCB1 3435 TT.RESULTS:
A total of 87 (3.97%) primary end-point events occurred (64 deaths, 8 non-fatal MIs and 15 strokes). Multivariate Cox analysis indicated that CYP2C19 PM+ABCB1 3435 TT status was a significant predictor of the primary end point (hazard ratio = 4.51, 95% confidence interval (CI) = 1.92-10.58). However, addition of combined genetic status to the clinical risk model did not improve the model discrimination (C-statistic = 0.786 (95% CI = 0.734-0.837) to 0.785 (95% CI = 0.733-0.838)) or risk reclassification (categorical net reclassification improvement (0.040, P = 0.32), integrated discrimination improvement (0.021, P = 0.026)).CONCLUSIONS:
In a real-world East Asian PCI population taking clopidogrel, although the concurrent presence of CYP2C19 PM and ABCB1 TT is a strong independent predictor of adverse outcomes, the combined status of two at-risk variants does not have an incremental prognostic value beyond that of the conventional clinical risk factors.Genet Med 18 8, 833-841.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Inhibidores de Agregación Plaquetaria
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Pueblo Asiatico
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Intervención Coronaria Percutánea
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Citocromo P-450 CYP2C19
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Mutación
Tipo de estudio:
Etiology_studies
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Prognostic_studies
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Risk_factors_studies
Límite:
Aged
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Aged80
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Female
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Humans
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Male
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Middle aged
País/Región como asunto:
Asia
Idioma:
En
Revista:
Genet Med
Asunto de la revista:
GENETICA MEDICA
Año:
2016
Tipo del documento:
Article