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

CYP2C19 metabolises clopidogrel but also many non-antiplatelet substrates (PPIs, SSRIs, tricyclic antidepressants): metaboliser status extends well beyond antiplatelet selection.

CYP2C19 genotyping is recommended to guide antiplatelet selection after ischaemic stroke or TIA; this study quantifies exposure to other CYP2C19 substrates in the same patients. Retrospective longitudinal cohort of patients discharged from a tertiary stroke unit between October 2023 and November 2024, with at least one year of follow-up using linked primary care prescribing data. Among 502 patients on antiplatelet therapy at discharge, 81% were co-prescribed at least one non-antiplatelet CYP2C19 substrate: proton pump inhibitors first (80%), then SSRIs (5.4%) and tricyclics (3.6%). In the 329 patients with longitudinal data, exposure rose to 83% and antidepressant prescribing roughly doubled, with exposure to two or more substrates increasing from 8% to 19%. Applying population metaboliser frequencies, about one third of these prescriptions could have actionable implications.

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

This is the most useful logistical and economic argument for CYP2C19 genotyping in stroke care: a test performed once for antiplatelet selection remains usable for years for PPIs and antidepressants, with exposure increasing over time. The limitation is clear: no patient was actually genotyped, the actionable proportion is extrapolated from population phenotype frequencies, and the study is single-centre. What the work does highlight well is the gap it points to — there is no practical framework for reusing a genotype result beyond its original indication.

Analysis by Dr Thibaut Benquey