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December 28, 2020PLoS ONEOpen Access

CYP2C19*2 carriers on clopidogrel show higher platelet reaction units but zero high-on-treatment platelet reactivity.

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Why the study?

Responsiveness to clopidogrel varies among patients, and it was unclear whether specific SNPs in key hepatic enzymes or the ADP receptor are associated with high-on-treatment platelet reactivity.

Are specific genetic polymorphisms in key hepatic enzymes or the ADP receptor associated with high-on-treatment platelet reactivity in patients with ischemic stroke and TIAs receiving clopidogrel?

Population

103 patients with IS and TIAs receiving clopidogrel 75 mg/day

Comparison

Carriers vs non-carriers of eight SNPs in CYP2C19, CYP3A4, NR1I2, and P2Y12

Design

Observational study

Key result

In Danish patients with ischemic stroke or TIA on 75 mg/day clopidogrel, no patients exhibited high-on-treatment platelet reactivity, although CYP2C19*2 carriers had significantly higher platelet reaction units than non-carriers (median 129 vs 74, p<0.01).

Authors

CRCharlotte Lützhøft RathNJNiklas Rye JørgensenTWTroels Wienecke

Discussion

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Overview

No high-on-treatment reactivity despite higher PRU in CYP2C19*2 carriers supports standard dosing; leaves open genotyping utility in stroke/TIA.

Study Design

Type

Observational (n=103)

Multicenter

No

Structured PICO

Are specific genetic polymorphisms in key hepatic enzymes or the ADP receptor associated with high-on-treatment platelet reactivity in patients with ischemic stroke and TIAs receiving clopidogrel?

P
Population
103 adult patients with ischemic stroke or TIA receiving secondary prophylaxis with 75 mg clopidogrel daily, evaluated for platelet reactivity over a median of 69 days.
E
Exposure
Genotyping for eight different single nucleotide polymorphisms (SNPs) in the genes encoding CYP2C19, CYP3A4, NR1I2, and the P2Y12 receptor while on clopidogrel 75 mg/day.
C
Comparator
Non-carriers of the respective genetic polymorphisms.
O
Outcome
High-on-treatment platelet reactivity (HTPR) to clopidogrel and platelet reaction unit (PRU) values.surrogate

Main Result

Absolute Event Rate: 129% vs 74%

p-value: p=<0.01

In Danish patients with ischemic stroke or TIA, genetic polymorphisms including CYP2C19*2 do not lead to high-on-treatment platelet reactivity during long-term clopidogrel therapy.

Limitations

  • Small sample size preventing sub-group analysis on selected SNPs and interactions.
  • Potential selection bias as severely disabled stroke patients might hesitate to participate.
  • Lack of clinical endpoints to determine if different SNPs or phenotypic platelet resistance affect the risk of recurrent stroke or vascular events.

Cite This Study

Rath et al. (2020) conducted an observational in Ischemic stroke and transient ischemic attacks (n=103). CYP2C19*2 allele vs. Non-carriers was evaluated on Platelet reaction units (PRU) (p=<0.01). In Danish patients with ischemic stroke or TIA on 75 mg/day clopidogrel, no patients exhibited high-on-treatment platelet reactivity, although CYP2C19*2 carriers had significantly higher platelet reaction units than non-carriers (median 129 vs 74, p<0.01).

synapsesocial.com/papers/6aa4224dfd19ae9969b15a9ehttps://doi.org/10.1371/journal.pone.0236260
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Also Consider

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

  1. 1Influence of Genetic Polymorphisms on Clopidogrel Response and Clinical Outcomes in Patients with Acute Ischemic Stroke CYP2C19 Genotype on Clopidogrel Response2015 · 45 citations
  2. 2Association of clopidogrel high on-treatment reactivity with clinical outcomes and gene polymorphism in acute ischemic stroke patients2020 · 25 citations
  3. 3Association Between CYP2C19 Genotype and P2Y12 Reaction Units in Patients Receiving Clopidogrel After Acute Ischemic Stroke: A Prospective, Observational Study2026
  4. 4The <i>CYP2C19*2</i> and <i>CYP2C19*17</i> Polymorphisms play a Vital Role in Clopidogrel Responsiveness after Percutaneous Coronary Intervention: A Pharmacogenomics Study2017 · 19 citations
  5. 5CYP2C19 Polymorphisms and Antiplatelet Effects of Clopidogrel in Acute Ischemic Stroke in China2013 · 105 citations