Key result
Point-of-care CYP2C19 genotyping detects loss-of-function variants in ~26% of stroke patients but suffers frequent test failures.
Why the study?
Recent guidelines recommend pharmacogenetic testing before clopidogrel prescription to identify CYP2C19 loss-of-function variants associated with reduced drug efficacy.
Does point-of-care CYP2C19 genotyping identify loss-of-function variants and alter management in patients with IS/TIA or requiring angioplasty?
Observational (n=77)
No
Does point-of-care CYP2C19 genotyping identify loss-of-function variants and alter management in patients with IS/TIA or requiring angioplasty?
Point-of-care CYP2C19 genotyping in stroke patients successfully identifies clopidogrel resistance to guide alternative therapy, though high test failure rates present an implementation challenge.
Answers are grounded in this paper and cite their sources.
Caution with empiric clopidogrel in ischaemic stroke; extends pharmacogenetic evidence into Level 1 European guidelines.
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
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Nicholas Wetherall (2026) conducted an observational in Ischaemic stroke or transient ischaemic attack (n=77). Point-of-care CYP2C19 genotyping was evaluated on CYP2C19 loss-of-function (LOF) variants (*2 or *3) prevalence. Point-of-care CYP2C19 genotyping identified loss-of-function variants in 26% of stroke or TIA patients, but demonstrated a 20% test failure rate that may reduce cost efficiency.
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