RESUMEN
BACKGROUND: The loss-of-function genotype of cytochrome P450 2C19 (CYP2C19) has been proposed as a risk factor for stent thrombosis in patients with drug-eluting stent implantation. The aim of this study was to clarify the clinical features of patients with angioscopically-detected in-stent mural thrombi (ISMT). METHODS AND RESULTS: Enrolled were 100 stented segments in 55 patients with stable angina (20 bare-metal stents; 39 Cypher sirolimus-eluting stents [SES]; 26 Endeavor zotarolimus-eluting stents [ZES]; 13 Xience V everolimus-eluting stents; and 2 Nobori biolimus-eluting stents). Dual antiplatelet therapy (100 mg aspirin+75 mg clopidogrel once daily) had been continued since stenting. A poor metabolizer (PM) of clopidogrel was defined as a homozygote of CYP2C19 loss-of-function alleles. Coronary angioscopy revealed ISMT in 6 patients (5 SES, 1 ZES). Between the ISMT group and control group (n=49), there were no significant differences with regards to the VerifyNow P2Y12platelet function assay or in-stent endothelial coverage grade. Exact logistic regression analyses with stepwise forward selection at a significance level of 0.10 were performed to reveal predictive variables for ISMT (respectively: odds ratio, 95% confidence interval, P value: CYP2C19 PM genotype (3.28, 0.88-24.80, 0.09), SES implantation (3.37, 0.90-28.09, 0.08), and presence of yellow plaque (3.69, 1.14-25.70, 0.02). CONCLUSIONS: Patients with ISMT were characterized by SES implantation, poor clopidogrel metabolism, and in-stent yellow plaque.
Asunto(s)
Angioscopía , Trombosis Coronaria/etiología , Citocromo P-450 CYP2C19/genética , Stents Liberadores de Fármacos , Inhibidores de Agregación Plaquetaria/farmacocinética , Polimorfismo de Nucleótido Simple , Ticlopidina/análogos & derivados , Activación Metabólica/genética , Anciano , Alelos , Angina de Pecho/etiología , Aspirina/uso terapéutico , Clopidogrel , Angiografía Coronaria , Trombosis Coronaria/diagnóstico por imagen , Trombosis Coronaria/genética , Trombosis Coronaria/prevención & control , Citocromo P-450 CYP2C19/deficiencia , Citocromo P-450 CYP2C19/metabolismo , Resistencia a Medicamentos/genética , Quimioterapia Combinada , Stents Liberadores de Fármacos/clasificación , Femenino , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Inhibidores de Agregación Plaquetaria/uso terapéutico , Inhibidores de la Bomba de Protones/farmacología , Receptores Purinérgicos P2Y12/análisis , Ticlopidina/farmacocinética , Ticlopidina/uso terapéuticoRESUMEN
Objective The CYP2C19 loss-of-function (LoF) allele is present in half of the East Asian population and is associated with high on-treatment platelet reactivity (HTPR). This study aimed to investigate whether a rapid genotyping-guided approach is feasible and efficacious for selecting P2Y12 receptor blockers in Chinese patients suffering from acute coronary syndrome (ACS). Methods This was a single-centre, prospective, randomized, open-label study. A total of 132 patients with ACS were randomized to the rapid genotyping-guided treatment group (GG, N = 65) or the standard treatment group (SG, N = 67). Patients in the GG group were genotyped by the Verigene system. Patients with the CYP2C19 LoF allele were switched to ticagrelor and all remaining patients continued on clopidogrel. The endpoints were HTPR at 24 hours after the first loading dose of clopidogrel and 1 month afterwards. Results Forty patients in the GG group switched to ticagrelor, while others continued on clopidogrel. The incidence of HTPR in the GG vs SG groups was 9.2% vs 40.3% at 24 hours and 6.5% vs 32.3% at 1 month, respectively. Rapid point-of-care genotyping showed 100% concordance with conventional genotyping by real-time polymerase chain reaction. Conclusions In Chinese patients suffering from ACS, the rapid genotyping-guided approach for selecting P2Y12 receptor blockers is feasible and reduces the incidence of HTPR. Clinical Trial Registration URL: http://clinicaltrials.gov . Unique identifier: NCT01994941.