ABSTRACT NUMBER: ESOC2026YS108 POINT-OF-CARE CYP2C19 GENOTYPING IN A UK STROKE CENTRE: CLINICAL UTILITY AND IMPLEMENTATION CHALLENGES

Abstract Background and aims Clopidogrel is an antiplatelet drug used in the secondary prevention of cerebrovascular disease, ischaemic heart disease, and peripheral arterial disease. It is a pro-drug that requires hepatic conversion via the CYP2C19 enzyme to generate its active metabolite. Recent guidelines recommend pharmacogenetic (PGx) testing prior to clopidogrel prescription to identify CYP2C19 loss-of-function (LOF) variants associated with reduced efficacy. Methods We conducted point-of-care (POC) CYP2C19 genotyping using Genomadix Cube in 77 participants at a tertiary stroke centre. Eligible participants included individuals presenting with ischaemic stroke (IS) or transient ischaemic attack (TIA) despite clopidogrel secondary prevention, as well as those requiring angioplasty, irrespective of prior clopidogrel exposure. Results Overall, 26% (n=19) of participants carried one or more CYP2C19 LOF variants (*2 or *3), conferring a clopidogrel-resistant phenotype. All but one of these participants were switched to an alternative antiplatelet regimen in accordance with clinical guidelines; the remaining individual was commenced on apixaban following a new diagnosis of atrial fibrillation. At three-month follow-up, no clopidogrel-resistant participants experienced recurrent IS or TIA. The most frequent genotypes were *1/*1 and *1/*17, each occurring in 33% (n=24) of participants. A total of 86 test kits were used, with five participants remaining inconclusive despite repeat testing. Repeat testing accounted for 12 kits, yielding an overall failure rate of 20% (n=17). While prior studies demonstrate that CYP2C19 PGx testing is cost-effective, this pilot identified a relatively high POC test failure rate, which may reduce overall cost efficiency and should be considered when selecting testing modalities. Twelve-month follow-up is ongoing. Conflict of interest Nicholas Wetherall: Nothing to disclose