Evidence map›Paper›PMID 33611730›Full record

ArticleTranslational stroke research2022

CYP2C19 Loss-of-Function Associated with First-Time Ischemic Stroke in Non-surgical Asymptomatic Carotid Artery Stenosis During Clopidogrel Therapy.

Pious D Patel, Xinnan Niu, Chevis N Shannon, Joshua C Denny, Josh F Peterson, Matthew R Fusco, Rohan V Chitale

Open access · greenAbstract read
In one paragraph

Article in Translational stroke research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed, 2 pooled it
0.8field-weighted citation impact, top 27% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed, 2 syntheses or guidelines pooled it, 5 citations in OpenAlex.

  1. Pooled it
  2. The role ofExpert review of clinical pharmacology · 2022
    Pooled it
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 2 institutions in 1 country.

Pious D PatelVanderbilt University School of Medicine, 1161 21st Ave S # D3300, Nashville, TN, 37232, USA. pious.d.patel@vanderbilt.edu.ORCID 0000-0001-5398-2085
Xinnan NiuDepartment of Biomedical Informatics, Vanderbilt University Medical Center, Nashville, TN, USA.
Chevis N ShannonSurgical Outcomes Center for Kids, Monroe Carell Jr. Children's Hospital at Vanderbilt, Nashville, TN, USA.
Joshua C DennyDepartment of Biomedical Informatics, Vanderbilt University Medical Center, Nashville, TN, USA.
Josh F PetersonDepartment of Biomedical Informatics, Vanderbilt University Medical Center, Nashville, TN, USA.
Matthew R FuscoSurgical Outcomes Center for Kids, Monroe Carell Jr. Children's Hospital at Vanderbilt, Nashville, TN, USA.
Rohan V ChitaleSurgical Outcomes Center for Kids, Monroe Carell Jr. Children's Hospital at Vanderbilt, Nashville, TN, USA.
Monroe Carell Jr. Children's Hospital · USVanderbilt University Medical Center · US

Funding

Vanderbilt Institute for Clinical and Translational Research (VICTR) -Identifying correlates of functional immunity in SARS-CoV-2 convalescent plasmaUL1TR002243 · NCATS · VANDERBILT UNIVERSITY MEDICAL CENTER · PI Paul A. Harris, Wesley H Self · 2017 to 2026
$130.7M
VANDERBILT UNIVERSITY CTSA FOR PEDIATRIC RESEARCHUL1RR024975 · NCRR · VANDERBILT UNIVERSITY · PI BERNARD, GORDON RAPHAEL · 2007 to 2011
$45.7M
The Vanderbilt Institute for Clinical and Translational Research (VICTR)UL1TR000445 · NCATS · VANDERBILT UNIVERSITY MEDICAL CENTER · PI BERNARD, GORDON RAPHAEL · 2012 to 2016
$41.4M
PHARMACOGENOMICS OF ARRHYTHMIA THERAPYU01HL065962 · NHLBI · VANDERBILT UNIVERSITY · PI RODEN, DAN M · 2001 to 2009
$24.8M
Pharmacogenomics of Arrhythmia TherapyU19HL065962 · NHLBI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI RODEN, DAN M · 2010 to 2014
$17.4M
Understanding and preventing HLA-associated drug reactionsP50GM115305 · NIGMS · VANDERBILT UNIVERSITY MEDICAL CENTER · PI PHILLIPS, ELIZABETH · 2015 to 2019
$13.0M
The Genetic Epemiology of Multiple SclerosisR01NS032830 · NINDS · VANDERBILT UNIVERSITY · PI HAINES, JONATHAN L · 1995 to 2010
$8.9M
Epidemiologic Architecture for Genes Linked to Environment (EAGLE)U01HG004798 · NHGRI · VANDERBILT UNIVERSITY · PI CRAWFORD, DANA C · 2008 to 2013
$8.8M
Integrated, Individualized, and Intelligent Prescribing (I3P) Clinical Trial NetworkU01HG010232 · NHGRI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI CAVANAUGH, KERRI, PETERSON, JOSEPH F. · 2018 to 2024
$8.2M
VESPA: Vanderbilt Electronic Systems for Pharmacogenomic AssessmentRC2GM092618 · NIGMS · VANDERBILT UNIVERSITY · PI DENNY, JOSHUA C., RODEN, DAN M · 2009 to 2010
$6.4M
Vanderbilt Genome Electronic Records ProjectU01HG006378 · NHGRI · VANDERBILT UNIVERSITY · PI RODEN, DAN M · 2011 to 2014
$4.0M
Understanding the genetic risk underlying racial disparities in uterine fibroids - Diversity SupplementR01HD074711 · NICHD · VANDERBILT UNIVERSITY MEDICAL CENTER · PI VELEZ EDWARDS, DIGNA R · 2013 to 2017
$2.9M
NCATS NIH HHS UL1 TR000445NCATS NIH HHS UL1 TR002243NCRR NIH HHS S10 RR025141NCRR NIH HHS UL1 RR024975NHGRI NIH HHS U01 HG004798NHGRI NIH HHS U01 HG006378NHGRI NIH HHS U01 HG010232NHLBI NIH HHS U01 HL065962NHLBI NIH HHS U19 HL065962NICHD NIH HHS R01 HD074711NIGMS NIH HHS P50 GM115305NIGMS NIH HHS RC2 GM092618NIH HHS U01HG010232NINDS NIH HHS R01 NS032830
6 · The paper itself

Abstract

This study measures effect of CYP2C19 genotype on ischemic stroke risk during clopidogrel therapy for asymptomatic, extracranial carotid stenosis patients. Using deidentified electronic health records, patients were selected for retrospective cohort using administrative code for carotid stenosis, availability of CYP2C19 genotype result, clopidogrel exposure, and established patient care. Patients with intracranial atherosclerosis, aneurysm, arteriovenous malformation, prior ischemic stroke, or observation time <1 month were excluded. Dual antiplatelet therapy patients were included. Patients with carotid endarterectomy or stenting were analyzed in a separate subgroup. Time-to-event analysis using Cox regression was conducted to model ischemic stroke events based on CYP2C19 loss-of-function allele and adjusted with the most predictive covariates from univariate analysis. Covariates included age, gender, race, length of aspirin, length of concurrent antiplatelet/anticoagulant treatment, diabetes, coagulopathy, hypertension, heart disease, atrial fibrillation, and lipid disorder. A total of 1110 patients met selection criteria for medical therapy cohort (median age 68 [interquartile range (IQR) 60-75] years, 64.9% male, 91.9% Caucasian). Median study period was 2.8 [0.8-5.3] years. A total of 47 patients (4.2%) had an ischemic stroke event during study period. CYP2C19 loss-of-function allele was strongly associated with ischemic stroke events (one allele: HR 2.3, 95% CI 1.1-4.7, p=0.020; two alleles: HR 10.2, 95% CI 2.8-36.8, p<0.001) after adjustment. For asymptomatic carotid stenosis patients receiving clopidogrel to prevent ischemic stroke, CYP2C19 loss-of-function allele is associated with 2- to 10-fold increased risk of ischemic stroke. CYP2C19 genotype may be considered when selecting antiplatelet therapy for stroke prophylaxis in non-procedural, asymptomatic carotid stenosis.

Indexed as

Carotid StenosisIschemic Attack, TransientIschemic StrokeStrokeAgedClopidogrelCytochrome P-450 CYP2C19FemaleHumansMaleMiddle AgedPlatelet Aggregation InhibitorsRetrospective StudiesTreatment OutcomeClopidogrelCYP2C19 protein, humanCytochrome P-450 CYP2C19Platelet Aggregation InhibitorsCarotid stenosisClopidogrelCYP2C19Ischemic strokePharmacogenetics

Identifiers

PMID33611730
PMCPMC9722320
OpenAlexW3131815029

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.