RESUMEN
BACKGROUND: CYP2C19 loss-of-function (LOF) alleles impair clopidogrel effectiveness after percutaneous coronary intervention. The feasibility, sustainability, and clinical impact of using CYP2C19 genotype-guided dual antiplatelet therapy (DAPT) selection in practice remains unclear. METHODS: A single-center observational study was conducted in 1193 patients who underwent percutaneous coronary intervention and received DAPT after implementation of an algorithm that recommends CYP2C19 testing in high-risk patients and alternative DAPT (prasugrel or ticagrelor) in LOF allele carriers. The frequency of genotype testing and alternative DAPT selection were the primary implementation end points. Risk of major adverse cardiovascular or cerebrovascular and clinically significant bleeding events over 12 months were compared across genotype and DAPT groups by proportional hazards regression. RESULTS: CYP2C19 genotype was obtained in 868 (72.8%) patients. Alternative DAPT was prescribed in 186 (70.7%) LOF allele carriers. CYP2C19 testing (P<0.001) and alternative DAPT use in LOF allele carriers (P=0.001) varied over time. Risk for major adverse cardiovascular or cerebrovascular was significantly higher in LOF carriers prescribed clopidogrel versus alternative DAPT (adjusted hazard ratio, 4.65; 95% confidence interval, 2.22-10.0; P<0.001), whereas no significant difference was observed in those without a LOF allele (adjusted hazard ratio, 1.37; 95% confidence interval, 0.72-2.85; P=0.347). Bleeding event rates were similar across groups (log-rank P=0.816). CONCLUSIONS: Implementing CYP2C19 genotype-guided DAPT is feasible and sustainable in a real-world setting but challenging to maintain at a consistently high level of fidelity. The higher risk of major adverse cardiovascular or cerebrovascular associated with clopidogrel use in CYP2C19 LOF allele carriers suggests that use of genotype-guided DAPT in practice may improve clinical outcomes.
Asunto(s)
Clopidogrel/administración & dosificación , Enfermedad Coronaria/cirugía , Citocromo P-450 CYP2C19/genética , Intervención Coronaria Percutánea , Pruebas de Farmacogenómica/métodos , Variantes Farmacogenómicas , Inhibidores de Agregación Plaquetaria/administración & dosificación , Clorhidrato de Prasugrel/administración & dosificación , Ticagrelor/administración & dosificación , Anciano , Toma de Decisiones Clínicas , Clopidogrel/efectos adversos , Clopidogrel/metabolismo , Enfermedad Coronaria/sangre , Enfermedad Coronaria/diagnóstico , Citocromo P-450 CYP2C19/metabolismo , Estudios de Factibilidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , North Carolina , Selección de Paciente , Intervención Coronaria Percutánea/instrumentación , Inhibidores de Agregación Plaquetaria/efectos adversos , Inhibidores de Agregación Plaquetaria/metabolismo , Clorhidrato de Prasugrel/efectos adversos , Clorhidrato de Prasugrel/metabolismo , Valor Predictivo de las Pruebas , Reproducibilidad de los Resultados , Estudios Retrospectivos , Factores de Riesgo , Stents , Ticagrelor/efectos adversos , Ticagrelor/metabolismo , Resultado del TratamientoRESUMEN
AIM: Determine whether using CYP2C19 genotype to optimize antiplatelet therapy selection is cost effective over the initial 30 days and 1-year following percutaneous coronary intervention. MATERIALS & METHODS: A cost-effectiveness analysis compared 30-day and 1-year outcomes and cost across three treatment strategies (universal clopidogrel, universal prasugrel, genotype-guided) in a hypothetical cohort. RESULTS: Base-case scenario results at 30 days indicated that the incremental cost per major cardiovascular or bleeding event avoided for genotype-guided treatment was US$8525 and US$42,198 compared with universal clopidogrel and prasugrel, respectively. Probabilistic sensitivity analysis demonstrated that genotype-guided treatment was cost effective over 30 days and 1 year in 62 and 70% of simulations, respectively. CONCLUSION: Implementing a CYP2C19 genotype-guided approach to antiplatelet therapy could have a positive economic impact by preventing readmissions following percutaneous coronary intervention.
Asunto(s)
Citocromo P-450 CYP2C19/genética , Inhibidores de Agregación Plaquetaria/economía , Inhibidores de Agregación Plaquetaria/uso terapéutico , Síndrome Coronario Agudo/tratamiento farmacológico , Clopidogrel , Análisis Costo-Beneficio/métodos , Costos de los Medicamentos , Genotipo , Hemorragia/tratamiento farmacológico , Humanos , Intervención Coronaria Percutánea , Clorhidrato de Prasugrel/economía , Clorhidrato de Prasugrel/uso terapéutico , Ticlopidina/análogos & derivados , Ticlopidina/economía , Ticlopidina/uso terapéuticoRESUMEN
AIM: An algorithm that uses clinical factors and CYP2C19 genotype to guide P2Y12 inhibitor selection in high-risk patients undergoing percutaneous coronary intervention was implemented at our institution. We sought to evaluate use of this algorithm and identify which factors influenced P2Y12 inhibitor selection. PATIENTS & METHODS: This retrospective cohort study included 264 patients receiving percutaneous coronary intervention from July-December 2012. RESULTS: CYP2C19 genotype was obtained in 229 patients; of these, 30% were intermediate or poor metabolizers. CYP2C19 intermediate or poor metabolizer phenotype was among the strongest predictors for selecting prasugrel or ticagrelor as maintenance therapy (p < 0.001), and was the only significant predictor of a change in therapy (p < 0.001). CONCLUSION: These findings suggest that using CYP2C19 genotype to guide P2Y12 inhibitor selection is feasible. Original submitted 27 October 2014; revision submitted 19 December 2014.