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May 8, 2026European Stroke JournalOpen Access

Abstract Number: Esoc2026a1313 Relationship Between Cyp2c19 and Other Genotypes With on-Treatment Platelet Reactivity Status on Clopidogrel in Tia/Ischaemic Stroke Patients in Ireland

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Key result

The rs10509646 SNP in the HHEX gene was associated with higher on-treatment platelet reactivity on clopidogrel in TIA/ischaemic stroke patients (P=0.0003 for PFA-100 closure times).

Why the study?

Few studies had concurrently assessed the influence of CYP2C19 and other pharmacogenetic factors on clopidogrel high on-treatment platelet reactivity status and outcomes in cerebrovascular disease patients.

Do CYP2C19 and other genotypes influence on-treatment platelet reactivity status in TIA/ischaemic stroke patients on clopidogrel?

Population

94 TIA-ischaemic stroke patients

Comparison

CYP2C19 and other genotypes in clopidogrel-treated patients

Design

Prospective pilot-observational study

Authors

DSDeirdre SmithINIryna NaydonovaCOChika Offiah

Discussion

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Overview

CYP2C19 LOF alone cannot reliably predict clopidogrel HTPR in CVD; leaves open additional loci like HHEX for validation studies.

Key Points

  • This research aims to evaluate the impact of CYP2C19 polymorphisms and other genotypes on Clopidogrel-induced platelet reactivity in cerebrovascular disease patients.
  • 94 TIA-ischaemic stroke patients analyzed for CYP2C19 genotypes and candidate SNPs including RAD18, ASIC2, CYP2C18.
  • Platelet reactivity was measured using PFA-100 and VerifyNow assays to categorize HTPR status.
  • Pilot GWAS was conducted to identify associations with HTPR.
  • 29% were predicted Poor-Intermediate, 37% Normal, and 34% Rapid-Ultrarapid CYP2C19 Metabolisers.
  • 33% of Poor-Intermediate Metabolisers had adequate platelet inhibition despite expected HTPR.
  • Significant association found between rs10509646 SNP and on-treatment platelet reactivity with P-values of 0.0003 and 0.005.

Study Design

Type

Observational (n=94)

Multicenter

Yes

Structured PICO

Do CYP2C19 and other genotypes influence on-treatment platelet reactivity status in TIA/ischaemic stroke patients on clopidogrel?

P
Population
94 TIA-ischaemic stroke patients in the prospective Optimal Antiplatelet Therapy in TIA and Ischaemic Stroke-International pilot-observational study
I
Intervention
Clopidogrel therapy with pharmacogenetic analysis (CYP2C19, RAD18, ASIC2, CYP2C18, HHEX)
O
Outcome
Clopidogrel-High on-Treatment Platelet Reactivity (HTPR) status measured by PFA-100, VerifyNow, and PL-12/Aggrestar ADP assayssurrogate

Main Result

p-value: p=0.0003

Up to 33% of TIA/stroke patients predicted to be poor-intermediate CYP2C19 metabolizers still achieve adequate P2Y12-inhibition on clopidogrel, and novel SNPs like HHEX may also influence platelet reactivity.

Cite This Study

Smith et al. (2026) conducted an observational in TIA and Ischaemic Stroke (n=94). Clopidogrel was evaluated on On-treatment platelet reactivity (PFA-100 closure times and VerifyNow P2Y12-Reactivity Units) (p=0.0003). The rs10509646 SNP in the HHEX gene was associated with higher on-treatment platelet reactivity on clopidogrel in TIA/ischaemic stroke patients (P=0.0003 for PFA-100 closure times).

synapsesocial.com/papers/69fd7ee0bfa21ec5bbf073a0https://doi.org/10.1093/esj/aakag023.635
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