Cited by 17Antiplatelet Therapy and Cardiovascular DiseasesPharmacogenetics and Drug MetabolismBlood Coagulation and Thrombosis Mechanisms

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Risk of stroke in CYP2C19 LoF polymorphism carrier coronary artery disease patients undergoing clopidogrel therapy: An ethnicity-based updated meta-analysis

Jafrin, Sarah, Naznin, Nura Ershad, Reza, Md. Sharif, Aziz, Md. Abdul, Islam, Mohammad Safiqul·2021·European Journal of Internal Medicine

DOI 10.1016/j.ejim.2021.05.022

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Abstract

Background Antiplatelet agent clopidogrel has been widely used for stroke management for many years, although resistance to clopidogrel may increase the chance of stroke recurrence. CYP2C19 loss-of-function (LoF) polymorphism is assumed to be responsible for the poor metabolism of clopidogrel that ultimately turns to resistance. Previous publications could not provide firm evidence due to highly conflicting and heterogeneous outcomes.Aim To get clear evidence from an updated meta-analysis on CYP2C19 LoF polymorphism association with stroke risk in clopidogrel treated patients, this study has been performed.Methods We conducted a meta-analysis with 72 selected studies from authentic databases, including 40,035 coronary artery disease patients treated with clopidogrel.Results This analysis showed that the worldwide carrier of one or more CYP2C19 LoF alleles had a significantly higher risk of stroke and composite events than the non-LoF carriers (RR=1.78, 95% CI=1.52-2.07, p<0.00001 and RR=1.39, 95% CI=1.26-1.54, p<0.00001, respectively). Besides, subgroup analysis showed that Asian CYP2C19 LoF carriers had a significantly increased risk of stroke (RR=1.91, 95% CI=1.60-2.28, p<0.00001) while the risk of composite events was significantly higher in all ethnic populations (Asian: RR=1.58, 95% CI=1.32-1.89, p<0.00001; Caucasian: RR=1.27, 95% CI=1.08-1.50, p=0.003; Hispanic and others: RR=1.21, 95% CI=1.09-1.34, p=0.0003).Conclusion Our meta-analysis confirmed that the presence of CYP2C19 LoF alleles increases the risk of stroke and composite events recurrence in the worldwide population, especially in Asians undergoing clopidogrel treatment. Alternative antiplatelet therapy should be investigated thoroughly for the intermediate and poor metabolizers.

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Authors: Jafrin, S., Naznin, N. E., Reza, M. S., Aziz, M. A., & Islam, M. S.
Affiliations: Noakhali Science and Technology University (BD)
Corresponding author: Islam, Mohammad Safiqul
ORCID: Jafrin, Sarah
Reza, Md. Sharif
Aziz, Md. Abdul
Islam, Mohammad Safiqul
Venue: European Journal of Internal Medicine
Publisher: Elsevier BV
Published: 2021-08
Volume: 90
Pages: 49-65
ISSN: 0953-6205 (ISSN-L)
DOI: 10.1016/j.ejim.2021.05.022
OpenAlex: W3171783709
Cited by: 17
References: 107
Citations by year: 2026: 5 · 2024: 1 · 2023: 3 · 2022: 7 · 2021: 1
FWCI: 0.59
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
Locations: European Journal of Internal Medicine (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Antiplatelet Therapy and Cardiovascular Diseases
Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
Health Sciences › Medicine › Hematology › Blood Coagulation and Thrombosis Mechanisms
Keywords: clopidogrel, clopidogrel resistance, stroke risk, coronary artery disease, antiplatelet therapy, ethnic differences, Asian patients, poor metabolizers
MeSH terms: Clopidogrel, Coronary Artery Disease, Ethnicity, Genotype, Humans, Platelet Aggregation Inhibitors, Treatment Outcome, Stroke, Cytochrome P-450 CYP2C19

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Risk of stroke in CYP2C19 LoF polymorphism carrier coronary artery disease patients undergoing clopidogrel therapy: An ethnicity-based updated meta-analysis

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