Exposure to CYP2C19‐metabolized drugs following acute stroke: A longitudinal cohort study to inform implementation of CYP2C19 genotype testing

AIMS: Cytochrome P450 2C19 (CYP2C19) genotype testing is recommended to guide antiplatelet selection after ischaemic stroke and transient ischaemic attack. CYP2C19 also metabolizes several commonly prescribed non-antiplatelet drugs. We aimed to quantify exposure to CYP2C19-metabolized drugs in stroke patients at hospital discharge and during longitudinal follow-up. METHODS: We conducted a retrospective longitudinal cohort study of patients discharged following acute stroke from a tertiary care stroke unit between October 2023 and November 2024. Drugs with established CYP2C19 pharmacogenetic dosing guidance were identified. Exposure was assessed at discharge and over a minimum 1-year follow-up using linked primary care prescribing data. Population-level CYP2C19 metabolizer phenotype frequencies were applied to illustrate potential implications for genotype-informed prescribing. RESULTS: Among 502 patients prescribed antiplatelet therapy at discharge, 81% were co-prescribed at least one CYP2C19-metabolized non-antiplatelet drug. Proton pump inhibitors predominated (80%), followed by selective serotonin reuptake inhibitors (5.4%) and tricyclic antidepressants (3.6%). In 329 patients with longitudinal data, exposure increased to 83% during follow-up, with antidepressant prescribing approximately doubling. Exposure to two or more CYP2C19-metabolized drugs increased from 8% to 19%. Applying population metabolizer frequencies suggested around one third of CYP2C19-metabolized drug prescriptions at discharge, and during follow-up may have actionable implications. CONCLUSIONS: Exposure to CYP2C19-metabolized drugs is highly prevalent after acute stroke and increases over time, indicating that CYP2C19 genotype results obtained for antiplatelet selection are likely to have broader longitudinal relevance across commonly prescribed therapies. Guidance should be developed to assist clinicians to incorporate genotype results into prescribing decisions.