The DOI matches its Crossref record; 107 of the 107 references it cites were found in a registry or an index.
Risk of stroke in CYP2C19 LoF polymorphism carrier coronary artery disease patients undergoing clopidogrel therapy: An ethnicity-based updated meta-analysis
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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“Due to genetic differences in pharmacokinetics and pharmacodynamics, clopidogrel [29], phenytoin [30], warfarin [31], clozapine [32], and carbamazepine [33] also had variable efficacy and side-effect profiles in Western and non-Western individuals.”
From Hasty generalizations and generics in medical research: A systematic review (2024) · cites this paper as [29]
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Hasty generalizations and generics in medical research: A systematic review
Peters, U., Sherling, H. R., & Chin-Yee, B. (2024) · PLOS ONE · doi:10.1371/journal.pone.0306749 · Cited by 11
Metadata
- 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
- Venue
- European Journal of Internal Medicine
- Publisher
- Elsevier BV
- Published
- 2021-08
- Volume
- 90
- Pages
- 49-65
- ISSN
- 0953-6205 (ISSN-L)
- 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
- 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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