The DOI matches its Crossref record; 71 of the 71 references it cites were found in a registry or an index.
CYP2C19 Genotype, Clopidogrel Metabolism, Platelet Function, and Cardiovascular Events: A Systematic Review and Meta-analysis
Abstract
CONTEXT: The US Food and Drug Administration recently recommended that CYP2C19 genotyping be considered prior to prescribing clopidogrel, but the American Heart Association and American College of Cardiologists have argued evidence is insufficient to support CYP2C19 genotype testing. OBJECTIVE: To appraise evidence on the association of CYP2C19 genotype and clopidogrel response through systematic review and meta-analysis. DATA SOURCES: PubMed and EMBASE from their inception to October 2011. STUDY SELECTION: Studies that reported clopidogrel metabolism, platelet reactivity or clinically relevant outcomes (cardiovascular disease [CVD] events and bleeding), and information on CYP2C19 genotype were included. DATA EXTRACTION: We extracted information on study design, genotyping, and disease outcomes and investigated sources of bias. RESULTS: We retrieved 32 studies of 42,016 patients reporting 3545 CVD events, 579 stent thromboses, and 1413 bleeding events. Six studies were randomized trials ("effect-modification" design) and the remaining 26 reported individuals exposed to clopidogrel ("treatment-only" design). In treatment-only analysis, individuals with 1 or more CYP2C19 alleles associated with lower enzyme activity had lower levels of active clopidogrel metabolites, less platelet inhibition, lower risk of bleeding (relative risk [RR], 0.84; 95% CI, 0.75-0.94; absolute risk reduction of 5-8 events per 1000 individuals), and higher risk of CVD events (RR, 1.18; 95% CI, 1.09-1.28; absolute risk increase of 8-12 events per 1000 individuals). However, there was evidence of small-study bias (Harbord test P = .001). When analyses were restricted to studies with 200 or more events, the point estimate was attenuated (RR, 0.97; 95% CI, 0.86-1.09). In effect-modification studies, CYP2C19 genotype was not associated with modification of the effect of clopidogrel on CVD end points or bleeding (P > .05 for interaction for both). Other limitations included selective outcome reporting and potential for genotype misclassification due to problems with the * allele nomenclature for cytochrome enzymes. CONCLUSION: Although there was an association between the CYP2C19 genotype and clopidogrel responsiveness, overall there was no significant association of genotype with cardiovascular events.
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“Women and minorities have historically been under investigated and under-represented in clinical research 153 .”
From Integrating genomics with biomarkers and therapeutic targets to invigorate cardiovascular drug development (2021) · cites this paper as [153]
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Zanger, U. M., & Schwab, M. (2013) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2012.12.007 · Cited by 4,169
“, 2011), associationwith clopidogrel metabolic concentration and platelet reactivity responsiveness but no overall associationwith cardiovascular events in another one (Holmes et al., 2011), while the most recent study, which analyzed 16 clinical studies, confirmed significant associations with major cardiovascular en…”
ResultJneid, H. M., Anderson, J. L., Wright, R. S., Adams, C. D., Bridges, C. R., Casey, D. E., Ettinger, S. M., Fesmire, F. M., Ganiats, T. G., Lincoff, A. M., et al. (2012) · Circulation · doi:10.1161/cir.0b013e318256f1e0 · Cited by 1,091
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Anderson, J. L., Adams, C. D., Antman, E. M., Bridges, C. R., Califf, R. M., Casey, D. E., Chavey, W. E., Fesmire, F. M., Hochman, J. S., Levin, T. N., et al. (2013) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2013.01.014 · Cited by 967
Implementing genomic medicine in the clinic: the future is here
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Metadata
- Authors
- Holmes, M. V., Perel, P., Shah, T., Hingorani, A. D., & Casas, J. P.
- Affiliations
- University College London (GB)
- Northwestern University (US)
- Venue
- JAMA
- Publisher
- American Medical Association (AMA)
- Published
- 2011-12-28
- Volume
- 306
- Issue
- 24
- Pages
- 2704
- ISSN
- 0002-9955 (ISSN-L)
- 0098-7484
- OpenAlex
- W2119186881
- Cited by
- 472
- References
- 70
- Citations by year
- 2026: 10 · 2025: 10 · 2024: 7 · 2023: 13 · 2022: 18 · 2021: 22 · 2020: 19 · 2019: 27 · 2018: 23 · 2017: 25 · 2016: 36 · 2015: 46 · 2014: 53 · 2013: 89 · 2012: 70
- FWCI
- 47.48
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- JAMA (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute for Health and Care Research (RP-PG-0407-10314)
- British Heart Foundation (FS05/125)
- 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 › Cardiology and Cardiovascular Medicine › Coronary Interventions and Diagnostics
- Keywords
- CYP2C19 genotype, clopidogrel, clopidogrel response, platelet function, platelet aggregation inhibition, cardiovascular events, bleeding risk, stent thrombosis, genotype testing, pharmacogenetics, small-study bias, effect modification, clopidogrel resistance, clopidogrel hypersensitivity, clopidogrel metabolite
- MeSH terms
- Clopidogrel, Aryl Hydrocarbon Hydroxylases, Cardiovascular Diseases, Genotype, Hemorrhage, Humans, Platelet Aggregation, Platelet Aggregation Inhibitors, Platelet Function Tests, Risk, Thrombosis, Ticlopidine, Angioplasty, Balloon, Coronary, Randomized Controlled Trials as Topic, Cytochrome P-450 CYP2C19
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