CYP2C19 Loss-of-Function is Associated with Increased Risk of Ischemic Stroke after Transient Ischemic Attack in Intracranial Atherosclerotic Disease

Intracranial atherosclerotic disease (ICAD) is responsible for 8-10% of acute ischemic strokes, and resistance to antiplatelet therapy is prevalent. CYP2C19 gene loss-of-function (up to 45% of patients) causes clopidogrel resistance. For patients with asymptomatic ICAD and ICAD characterized by tran...

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Bibliographic Details
Published in:Journal of stroke and cerebrovascular diseases 2021-02, Vol.30 (2), p.105464-105464, Article 105464
Main Authors: Patel, Pious D., Vimalathas, Praveen, Niu, Xinnan, Shannon, Chevis N., Denny, Joshua C., Peterson, Josh F., Chitale, Rohan V., Fusco, Matthew R.
Format: Article
Language:English
Subjects:
Aged
Antiplatelet
Clopidogrel
Clopidogrel - administration & dosage
Clopidogrel - adverse effects
CYP2C19
Cytochrome P-450 CYP2C19 - genetics
Databases, Factual
Drug Resistance - genetics
Female
Humans
Intracranial Arteriosclerosis - complications
Intracranial Arteriosclerosis - diagnostic imaging
Intracranial Arteriosclerosis - drug therapy
Intracranial atherosclerosis
Intracranial stenosis
Ischemic Attack, Transient - diagnostic imaging
Ischemic Attack, Transient - etiology
Ischemic Attack, Transient - prevention & control
Ischemic stroke
Ischemic Stroke - diagnostic imaging
Ischemic Stroke - etiology
Ischemic Stroke - prevention & control
Male
Middle Aged
Pharmacogenetics
Pharmacogenomic Variants
Platelet Aggregation Inhibitors - administration & dosage
Platelet Aggregation Inhibitors - adverse effects
Retrospective Studies
Risk Assessment
Risk Factors
Time Factors
Treatment Outcome
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Summary:Intracranial atherosclerotic disease (ICAD) is responsible for 8-10% of acute ischemic strokes, and resistance to antiplatelet therapy is prevalent. CYP2C19 gene loss-of-function (up to 45% of patients) causes clopidogrel resistance. For patients with asymptomatic ICAD and ICAD characterized by transient ischemic attack (TIA), this study measures the effect of CYP2C19 loss-of-function on ischemic stroke risk during clopidogrel therapy. From a deidentified database of medical records, patients were selected with ICD-9/10 code for ICAD, availability of CYP2C19 genotype, clopidogrel exposure, and established patient care. Dual-antiplatelet therapy patients were included. Patients with prior ischemic stroke, other neurovascular condition, intracranial angioplasty/stenting, or observation time
ISSN:1052-3057
1532-8511
DOI:10.1016/j.jstrokecerebrovasdis.2020.105464