OBJECTIVES: To estimate the impact of preemptive genotyping in cardiac catheterization laboratory patients based on the number of clopidogrel, warfarin, and simvastatin prescribing changes recommended by the Clinical Pharmacogenetics Implementation Consortium (CPIC).
METHODS: A retrospective analysis was conducted in a cohort of patients referred for coronary angiography at UNC Hospitals from 2012 to 2014 who consented to participate in a single-center study with medication data available at discharge and follow-up (n¼122). Patient DNA samples were sequenced using a custom pull-down method for library preparation and next-generation sequencing using the Illumina HiSeq platform. Bioinformatic tools (i.e. Burrows-Wheeler aligner, Freebayes) were used for the genetic analysis, and a minimum sequencing depth of 20x was required for genotype and haplotype calling. Pharmacogenetic-guided drugs and genes included in the analysis were: clopidogrel (CYP2C19 *1, *2, *3, *17), simvastatin (SLCO1B1 rs4149056), and warfarin (CYP2C9 *1, *2, *3; VKORC1 rs9923231).
RESULTS: Prescription data for warfarin, clopidogrel, and simvastatin were available for all patients. Haplotype calling was successful in 118 patients (96.7%) for CYP2C19, 112 patients (91.8%) for CYP2C9/ VKORC1, and 122 patients (100%) for SLCO1B1. A total of 87 prescriptions were given for clopidogrel, warfarin, and simvastatin. Based on the CPIC guidelines, 17 of these prescriptions (19.5%) were eligible for a change in dose or drug. According to the presence of an at-risk genotype, the number of CPIC recommended prescribing changes included: 10 (16.9%) out of 59 patients on clopidogrel, 2 (18.2%) out of 11 patients on warfarin, and 5 (29.4%) out of 17 patients on simvastatin.
CONCLUSIONS: Adopting a preemptive genotyping intervention that multiplexes CYP2C19, CYP2C9/VKORC1, and SLCO1B1 would be relevant for approximately 1 out of 5 cardiac catheterization laboratory patients. Additional studies in larger cohorts are needed to confirm the generalizability of these findings.
