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May 8, 2026European Stroke Journal

Clopidogrel-HTPR linked to ~93% greater ischemic risk, whereas CYP2C19-LOF SNPs show no association.

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Why the study?

NICE 2024 guidelines recommend CYP2C19 genotyping alone in TIA/ischaemic stroke patients without assessment of clopidogrel high on-treatment platelet reactivity status.

Does Clopidogrel-High on-Treatment Platelet Reactivity (HTPR) or CYP2C19 genotyping predict subsequent vascular events in TIA/ischaemic stroke patients on clopidogrel?

Population

CVD patients on clopidogrel across 12 prospective studies with N=131-501 per study

Comparison

Presence vs absence of clopidogrel-HTPR and CYP2C19-LOF SNPs

Design

Systematic review and meta-analysis of prospective studies

Key result

Clopidogrel-High on-Treatment Platelet Reactivity significantly increased the risk of subsequent ischemic events (RR ≥1.93; 95% CI 1.58-2.36), whereas CYP2C19-LOF SNPs did not.

Authors

INIryna NaydonovaTMTheodorοs MavridisVTVasileios Tentolouris-Piperas

Discussion

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Member takes

Overview

Identifies clopidogrel-HTPR as high-risk marker in CVD; leaves open whether testing-guided therapy improves outcomes.**[[1]](https://pubmed.ncbi.nlm.nih.gov/29945766/)[[2]](https://www.researchgate.

Key Points

  • To analyze the relationship between clopidogrel high on-treatment platelet reactivity and pharmacogenetics profiling outcomes in TIA and ischaemic stroke patients.
  • Performed a systematic review and meta-analysis of 12 prospective studies
  • Analyzed clopidogrel HTPR status and CYP2C19 genotyping
  • Calculated risk ratios using a random-effects model
  • CVD patients with clopidogrel HTPR had a significantly higher risk of primary outcomes (RR ≥ 1.93; 95% CI: 1.58-2.36)
  • No significant risk increase associated with CYP2C19-LOF SNPs (RR ≥1.36; 95% CI: 0.94-1.98)
  • Results indicate the need for more prospective studies to combine data from pharmacogenetics and platelet reactivity testing.

Study Design

Type

Meta-Analysis

Multicenter

Yes

Structured PICO

Does Clopidogrel-High on-Treatment Platelet Reactivity (HTPR) or CYP2C19 genotyping predict subsequent vascular events in TIA/ischaemic stroke patients on clopidogrel?

P
Population
Cerebrovascular disease (TIA/ischaemic stroke) patients on clopidogrel monotherapy or combination therapy from 12 prospective studies. Studies were small-medium in size (N=131-501) and conducted in China or Japan.
I
Intervention
Clopidogrel-High on-Treatment Platelet Reactivity (HTPR) or CYP2C19 Loss of Function (LOF) Single Nucleotide Polymorphisms (SNPs)
C
Comparator
Patients without Clopidogrel-HTPR or without CYP2C19-LOF SNPs
O
Outcome
Composite of subsequent ischaemic stroke/TIA/myocardial infarction/vascular deathcomposite

Main Result

Effect estimate: RR ≥ 1.93 (95% CI 1.58-2.36)

Clopidogrel high on-treatment platelet reactivity, but not CYP2C19 loss-of-function SNPs alone, significantly predicts recurrent vascular events in TIA/ischemic stroke patients on clopidogrel.

Limitations

  • All studies were conducted in China or Japan
  • Studies were small-medium in size (N=131-501)

Cite This Study

Naydonova et al. (2026) conducted a meta-analysis in TIA/ischaemic stroke. Clopidogrel-High on-Treatment Platelet Reactivity (HTPR) vs. Without Clopidogrel-HTPR was evaluated on Subsequent ischaemic stroke/TIA/myocardial infarction/vascular death (RR ≥ 1.93, 95% CI 1.58-2.36). Clopidogrel-High on-Treatment Platelet Reactivity significantly increased the risk of subsequent ischemic events (RR ≥1.93; 95% CI 1.58-2.36), whereas CYP2C19-LOF SNPs did not.

synapsesocial.com/papers/69fd7ee0bfa21ec5bbf071edhttps://doi.org/10.1093/esj/aakag023.488
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1ABSTRACT NUMBER: ESOC2026A1313 RELATIONSHIP BETWEEN CYP2C19 AND OTHER GENOTYPES WITH ON-TREATMENT PLATELET REACTIVITY STATUS ON CLOPIDOGREL IN TIA/ISCHAEMIC STROKE PATIENTS IN IRELAND2026
  2. 2ABSTRACT NUMBER: ESOC2026A2297 USEFULNESS OF PHARMACOGENETIC DATA FOR PREDICTING VASCULAR OUTCOMES AND PHARMACODYNAMIC EFFICACY IN CLOPIDOGREL-TREATED ISCHEMIC STROKE PATIENTS2026
  3. 3Influence of Genetic Polymorphisms on Clopidogrel Response and Clinical Outcomes in Patients with Acute Ischemic Stroke CYP2C19 Genotype on Clopidogrel Response2015 · 45 citations
  4. 4ABSTRACT NUMBER: ESOC2026YS108 POINT-OF-CARE CYP2C19 GENOTYPING IN A UK STROKE CENTRE: CLINICAL UTILITY AND IMPLEMENTATION CHALLENGES2026
  5. 5Association Between CYP2C19 Genotype and P2Y12 Reaction Units in Patients Receiving Clopidogrel After Acute Ischemic Stroke: A Prospective, Observational Study2026