Trial reportEuropean heart journal2009
Genetic variation of CYP2C19 affects both pharmacokinetic and pharmacodynamic responses to clopidogrel but not prasugrel in aspirin-treated patients with coronary artery disease.
Trial report in European heart journal, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers, 2 of them syntheses that pooled 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.
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
64 citing papers in PubMed, 2 syntheses or guidelines pooled it, 264 citations in OpenAlex.
- Cytochrome P450 2C19 polymorphism is associated with poor clinical outcomes in coronary artery disease patients treated with clopidogrel.Molecular biology reports · 2011Pooled it
- Pooled it
- Clopidogrel in Critically Ill Patients.Clinical pharmacology and therapeutics · 2018Trial
- Effectiveness of clopidogrel dose escalation to normalize active metabolite exposure and antiplatelet effects in CYP2C19 poor metabolizers.Journal of clinical pharmacology · 2014Trial
- Higher body weight patients on clopidogrel maintenance therapy have lower active metabolite concentrations, lower levels of platelet inhibition, and higher rates of poor responders than low body weight patients.Journal of thrombosis and thrombolysis · 2014Trial
- Pharmacokinetics and pharmacodynamics following maintenance doses of prasugrel and clopidogrel in Chinese carriers of CYP2C19 variants.British journal of clinical pharmacology · 2012Trial
- Dispensing of actionable pharmacogenetic drugs among adults receiving cardiovascular disease medications in the Northern Netherlands: A serial cross-sectional study.Clinical pharmacology and therapeutics · 2026Article
- CYP2C19 Polymorphism and Platelet Aggregation-Associated Risks in Atrial Fibrillation Patients Undergoing PCI.Clinical and translational science · 2026Article
- Review
- Ultra-high throughput-based screening for the discovery of antiplatelet drugs affecting receptor dependent calcium signaling dynamics.Scientific reports · 2024Article
- Tailoring Antithrombotic Regimens for Percutaneous Coronary Intervention Patients with High Bleeding and Ischemic Risk (Reviews in cardiovascular medicine · 2023Review
- Antiplatelet Resistance: A Review of Concepts, Mechanisms, and Implications for Management in Acute Ischemic Stroke and Transient Ischemic Attack.Stroke (Hoboken, N.J.) · 2023Review
- Epilepsy and Attention Deficit Hyperactivity Disorder: Connection, Chance, and Challenges.International journal of molecular sciences · 2023Review
- Pharmacogenetics of P2YPharmacotherapy · 2023Review
- Pharmacogenetics of Antiplatelet Therapy.Annual review of pharmacology and toxicology · 2023Review
- Cardiovascular precision medicine - A pharmacogenomic perspective.Cambridge prisms. Precision medicine · 2023Review
- Impact of the ABCD-GENE Score on Clopidogrel Clinical Effectiveness after PCI: A Multi-Site, Real-World Investigation.Clinical pharmacology and therapeutics · 2022Article
- Antiplatelet response to clopidogrel is associated with a haplotype in CYP2C19 gene in Pakistani patients.Scientific reports · 2022Article
- Risk factors for adverse drug reactions associated with clopidogrel therapy.Open medicine (Warsaw, Poland) · 2022Article
- Comprehensive characterization of pharmacogenes in a Taiwanese Han population.Frontiers in genetics · 2022Article
4 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimsThe metabolic pathways leading to the formation of prasugrel and clopidogrel active metabolites differ. We hypothesized that decreased CYP2C19 activity affects the pharmacokinetic and pharmacodynamic response to clopidogrel but not prasugrel. METHODS AND
resultsNinety-eight patients with coronary artery disease (CAD) taking either clopidogrel 600 mg loading dose (LD)/75 mg maintenance dose (MD) or prasugrel 60 mg LD/10 mg MD were genotyped for variation in six CYP genes. Based on CYP genotype, patients were segregated into two groups: normal function (extensive) metabolizers (EM) and reduced function metabolizers (RM). Plasma active metabolite concentrations were measured at 30 min, 1, 2, 4, and 6 h post-LD and during the MD period on Day 2, Day 14, and Day 29 at 30 min, 1, 2, and 4 h. Vasodilator-stimulated phosphoprotein (VASP) and VerifyNow P2Y12 were measured predose, 2, and 24 +/- 4 h post-LD and predose during the MD period on Day 14 +/- 3 and Day 29 +/- 3. For clopidogrel, active metabolite exposure was significantly lower (P = 0.0015) and VASP platelet reactivity index (PRI, %) and VerifyNow P2Y(12) reaction unit (PRU) values were significantly higher (P < 0.05) in the CYP2C19 RM compared with the EM group. For prasugrel, there was no statistically significant difference in active metabolite exposure or pharmacodynamic response between CYP2C19 EM and RM. Variation in the other five genes demonstrated no statistically significant differences in pharmacokinetic or pharmacodynamic responses.
conclusionVariation in the gene encoding CYP2C19 in patients with stable CAD contributes to reduced exposure to clopidogrel's active metabolite and a corresponding reduction in P2Y(12) inhibition, but has no significant influence on the response to prasugrel.
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Registered trials
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.