Physician response to implementation of genotype-tailored antiplatelet therapy

Abstract

Physician responses to genomic information are vital to the success of precision medicine initiatives. We prospectively studied a pharmacogenomics implementation program for the propensity of clinicians to select antiplatelet therapy based on CYP2C19 loss-of-function variants in stented patients. Among 2,676 patients, 514 (19.2%) were found to have a CYP2C19 variant affecting clopidogrel metabolism. For the majority (93.6%) of the cohort, cardiologists received active and direct notification of CYP2C19 status. Over 12 months, 57.6% of poor metabolizers and 33.2% of intermediate metabolizers received alternatives to clopidogrel. CYP2C19 variant status was the most influential factor impacting the prescribing decision (hazard ratio [HR] in poor metabolizers 8.1, 95% confidence interval [CI] [5.4, 12.2] and HR 5.0, 95% CI [4.0, 6.3] in intermediate metabolizers), followed by patient age and type of stent implanted. We conclude that cardiologists tailored antiplatelet therapy for a minority of patients with a CYP2C19 variant and considered both genomic and nongenomic risks in their clinical decision-making.

Figure 1

Flow of patients through implementation program

Figure 2

Cumulative incidence of alternative antiplatelet therapy by CYP2C19 drug metabolism category (N=2676)

Figure 3

Response of individual higher-volume cardiologists with greater than 40 subjects in cohort in patient populations with and without a CYP2C19 loss-of-function variant

Figure 4

Cumulative incidence of genotype tailored therapy among patients with intermediate or poor metabolizer phenotype for clopidogrel by (A) bleeding risk and (B) timing of genotype (N=514) Bleeding risks include age ≥ 75, weight < 60 kg, history of cerebrovascular disease, or concomitant anticoagulation (warfarin, dabigatran, enoxaparin, fondaparinux, or rivaroxaban) at time of stent placement. Preemptive genotyping indicated result available prior to coronary stent placement. Post-procedure genotyping indicated result available within 30 days of coronary stent placement.