ArticleJournal of atherosclerosis and thrombosis2016
Association of Cytochrome P450 Genetic Variants with Clopidogrel Resistance and Outcomes in Acute Ischemic Stroke.
Article in Journal of atherosclerosis and thrombosis, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 4 of them syntheses that pooled it.
What it found
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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.
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.
Who cites it
31 citing papers in PubMed, 4 syntheses or guidelines pooled it, 56 citations in OpenAlex.
- The association of CYP2C19 LoF alleles with adverse clinical outcomes in stroke patients taking clopidogrel: An updated meta-analysis.Clinical and translational science · 2024Pooled it
- The role ofExpert review of clinical pharmacology · 2022Pooled it
- Platelet function/reactivity testing and prediction of risk of recurrent vascular events and outcomes after TIA or ischaemic stroke: systematic review and meta-analysis.Journal of neurology · 2020Pooled it
- Influences of genetic variants on stroke recovery: a meta-analysis of the 31,895 cases.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2019Pooled it
- Aspirin plus clopidogrel may reduce the risk of early neurologic deterioration in ischemic stroke patients carrying CYP2C19*2 reduced-function alleles.Journal of neurology · 2018Trial
- Concomitant Use of Proton-Pump Inhibitors and Clopidogrel Increases the Risk of Adverse Outcomes in Patients With Ischemic Stroke Carrying Reduced-Function CYP2C19*2.Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis · 2018Trial
- Association of Clopidogrel Genetic Polymorphism With Efficacy and Safety for Ischemic Stroke or Transient Ischemic Attack: A Systematic Review and Updated Meta-Analysis.Journal of clinical neurology (Seoul, Korea) · 2025Article
- The Frequency ofThe application of clinical genetics · 2025Article
- Additive interaction between CYP2C19AA gene polymorphism and Lp(a) on the prognosis of stroke patients.American journal of translational research · 2025Article
- Article
- Influence of CYP450 Enzymes and ABCB1 Polymorphisms on Clopidogrel Response in Moroccan Patients with Acute Coronary Syndromes.Pharmacogenomics and personalized medicine · 2023Article
- P2Y12 Reaction Units and Clinical Outcomes in Acute Large Artery Atherosclerotic Stroke: A Multicenter Prospective Study.Journal of atherosclerosis and thrombosis · 2023Article
- Article
- Targeting Platelet Activation Pathways to Limit Tumour Progression: Current State of Affairs.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Analysis ofBMJ open · 2021Article
- Characterization of CYP3A pharmacogenetic variation in American Indian and Alaska Native communities, targeting CYP3A4*1G allele function.Clinical and translational science · 2021Observational
- Association between CYP2C19 polymorphisms and clinical outcomes in patients undergoing stent procedure for cerebral artery stenosis.Scientific reports · 2021Article
- MicroRNA as Potential Biomarkers of Platelet Function on Antiplatelet Therapy: A Review.Frontiers in physiology · 2021Review
- Systematic Investigation of the Effect of Powerful Tianma Eucommia Capsule on Ischemic Stroke Using Network Pharmacology.Evidence-based complementary and alternative medicine : eCAM · 2021Article
- Body weight, CYP2C19, and P2Y12 receptor polymorphisms relate to clopidogrel resistance in a cohort of Chinese ischemic stroke patients with aspirin intolerance.European journal of clinical pharmacology · 2020Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimsClopidogrel is an antiplatelet drug primarily used to treat or prevent acute ischemic stroke (IS) or myocardial infarction (MI). This prodrug requires biotransformation to an active metabolite by cytochrome P450 (CYP) enzymes, and CYP single nucleotide polymorphisms (SNPs) could affect the efficiency of such biotransformation.
methodsA total of 375 consecutive IS patients were genotyped for eight CYP SNPs using mass spectrometry. Platelet aggregation activity was measured before and after the 7-10 day treatment. Gene-gene interactions were analyzed using generalized multifactor dimensionality reduction (GMDR) analysis. All patients received clopidogrel therapy and were followed up for six months. Primary outcomes were evaluated as a composite of recurrent ischemic stroke (RIS), MI, and death. The secondary outcome was the modified Rankin Scale (mRS).
resultsClopidogrel resistance occurred in 153 patients (40.8%). The frequency of CYP3A5 (rs776746) GG/AG and CYP2C19*2 (rs4244285) AA/AG genotypes was significantly higher in clopidogrel-resistant patients than in sensitive patients. There was a significant gene-gene interaction between CYP3A5 (rs776746) and CYP2C19*2 (rs4244285). CYP2C19*2 AA and its interaction with CYP3A5 GG were independent predictors of clopidogrel resistance and affected the activity of platelet aggregation. Diabetes mellitus, CYP2C19*2 (rs4244285), clopidogrel resistance, and the interaction of CYP2C19*2 with CYP3A5 were all independent risk factors for the primary outcomes of clopidogrel treatment. Clopidogrel-resistant patients were more likely to have poor outcomes (mRS ＞2 points) compared with clopidogrel-sensitive patients.
conclusionCYP SNPs and their interactions are associated with drug resistance and outcomes in acute IS patients.
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Registered trials
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