TCT-726 Residual Platelet Reactivity Threshold After Clopidogrel Loading Dose to Predict Long-term Clinical Outcome in Patients with Acute Coronary Syndrome: Insights from the RECLOSE2-ACS Study

Abstract

validated laboratory-based genotyping method. Methods: 74 stable CAD patients on clop 75 mg daily were tested by clinical nurses with no genetic laboratory experience and 1 hour of basic training on the device. The patients were defined as EM (*1/*1, *1/*17, *17/*17), RM (*1/*2A, *1/*8, *2A/*2A, *2A/*3). Genetic testing was conducted on 1 mL of whole blood using the Verigene® System and compared to an Affymetrix® DMET assay. Pharmacokinetic (PK) exposure to clop’s active metabolite (AM) was measured and platelet reactivity (PD) was assessed with the VerifyNowTM P2Y12 system (PRU) and VASP (PRI) assays. Results: There was an overall 99.9% concordance of marker-level data between the Verigene® and the reference (DMET ) in measuring the CYP2C19 markers of interest. There was a 100% agreement between Verigene® and the reference test in classifying the patients into established EM and RM groups. The POC assay identified 59 EM, 15 RM. The EM group had significantly lower PRU (LS means 158 vs. 212; p 0.003), and PRI (LS means 48 vs. 63, p 0.01) than RM group treated with clopidogrel 75 mg. The EM group also had significantly higher AM exposure by AUC(0-last) than the RM group (LS means 12.6 vs. 7.7; p 0.0009). Conclusions: This is the first report of a POC genetic testing platform performing a comprehensive CYP2C19 polymorphism characterization in CAD patients and validating the genotypes against the PK and PD phenotype. There was a high concordance between the two platforms in measuring the star allele marker data. The POC genetic test identified EM and RM phenotypes based on 11 gene variants with high accuracy and predicted a reduced platelet inhibition in response to clop. A rapid, reliable POC CYP2C19 genetic test could make clop pharmacogenetic testing feasible for all patients.