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November 20, 2015Journal of neurosurgeryOpen Access

CYP2C19 and CES1 polymorphisms and efficacy of clopidogrel and aspirin dual antiplatelet therapy in patients with symptomatic intracranial atherosclerotic disease

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Why the study?

Do CYP2C19 and CES1 polymorphisms affect the risk of recurrent ischemic events or death in adult symptomatic ICAD patients treated with clopidogrel and aspirin?

Population

188 adult symptomatic intracranial atherosclerotic disease patients from 3 medical centers, medically…

Comparison

Presence of CYP2C19 loss of function alleles or… vs Wild-type homozygotes

Design

Cohort

Follow-up

12 months

Authors

BHBrian L. HohUniversity of Florida YGYan GongPreventive Cardiology CMCaitrin W. McDonoughUniversity of Florida

Discussion

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Implication

Unexpected lower ischemic risk in CYP2C19 LOF carriers should not change clopidogrel practice in ICAD; leaves open prospective validation of genotyping.

Key Points

To investigate whether CYP2C19 and CES1 single-nucleotide polymorphisms correlate with clinical efficacy outcomes in patients with symptomatic intracranial atherosclerotic disease treated with clopidogrel and aspirin.
Enrolled 188 adult patients with symptomatic intracranial atherosclerotic disease receiving dual antiplatelet therapy across three medical centers (one prospective cohort and two retrospective DNA biorepositories).
Genotyped participants for CYP2C19 (*2, *3, *8, *17) and CES1 G143E variants and evaluated the primary composite endpoint of transient ischemic attack, stroke, myocardial infarction, or death at 12 months using multivariable logistic and Cox regression models.
The 12-month primary composite endpoint occurred in 14.9% of the 188 patients.
Carriers of CYP2C19 loss-of-function alleles (*2, *3, and *8) had significantly lower odds (OR 0.13, 95% CI 0.03–0.62, p = 0.0101) and hazard (HR 0.27, 95% CI 0.08–0.95, p = 0.041) of the primary endpoint compared with wild-type homozygotes.
A secondary composite endpoint of transient ischemic attack, stroke, or death showed a similar protective trend for loss-of-function allele carriers (OR 0.27, 95% CI 0.06–1.16, p = 0.078; HR 0.22, 95% CI 0.05–1.04, p = 0.056).

Structured PICO

Do CYP2C19 and CES1 polymorphisms affect the risk of recurrent ischemic events or death in adult symptomatic ICAD patients treated with clopidogrel and aspirin?

P

Population

188 adult symptomatic intracranial atherosclerotic disease (ICAD) patients from 3 medical centers, medically managed with clopidogrel and aspirin

I

Intervention

Presence of CYP2C19 loss of function (LOF) alleles (*2, *3, and *8) or CES1 G143E polymorphisms

C

Comparator

Wild-type homozygotes

O

Outcome

Composite of transient ischemic attack (TIA), stroke, myocardial infarction, or death within 12 monthscomposite

CYP2C19 loss-of-function alleles were unexpectedly associated with a lower risk of ischemic events and death in symptomatic ICAD patients treated with clopidogrel and aspirin.

Cite This Study

Hoh et al. (2015) studied this question.

synapsesocial.com/papers/6a7d31f7166e996abdd5a665 https://doi.org/10.3171/2015.6.jns15795

Topics

Dual antiplatelet therapy

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Also Consider

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

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