ArticleEuropean heart journal. Cardiovascular pharmacotherapy2020
Pharmacogenomic polygenic response score predicts ischaemic events and cardiovascular mortality in clopidogrel-treated patients.
Article in European heart journal. Cardiovascular pharmacotherapy, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 59 papers, 2 of them syntheses that pooled it.
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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.
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Who cites it
59 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- Clinically important alterations in pharmacogene expression in histologically severe nonalcoholic fatty liver disease.Nature communications · 2023Pooled it
- Global distribution of CYP2C19 risk phenotypes affecting safety and effectiveness of medications.The pharmacogenomics journal · 2021Pooled it
- Randomized evaluation of the loss-of-function carboxylesterase 1 (CES1) G143E variant on clopidogrel and ticagrelor pharmacodynamics.Clinical and translational science · 2024Trial
- Pharmacogenomics polygenic risk score for drug response prediction using PRS-PGx methods.Nature communications · 2022Trial
- Genetic Variation in PEAR1, Cardiovascular Outcomes and Effects of Aspirin in a Healthy Elderly Population.Clinical pharmacology and therapeutics · 2020Trial
- Recent research progress on the mechanisms of clopidogrel resistance.European journal of clinical pharmacology · 2026Review
- The association of ABCB1, CYP2C19 and CYP2C9 combined activity with clopidogrel resistance in patients with recurrent ischemic stroke.The pharmacogenomics journal · 2026Article
- Custom Gene Panel Analysis Identifies Novel Polymorphisms Associated with Clopidogrel Response in Patients Undergoing Percutaneous Coronary Intervention with Stent.International journal of molecular sciences · 2025Article
- CYP2C19 Polymorphisms and Clinical Outcomes Following Percutaneous Coronary Intervention in the Million Veteran Program.Clinical pharmacology and therapeutics · 2025Article
- Pathway-Specific Polygenic Scores for Predicting Clinical Lithium Treatment Response in Patients With Bipolar Disorder.Biological psychiatry global open science · 2025Article
- A narrative review of research advancements in pharmacogenetics of cardiovascular disease and impact on clinical implications.NPJ genomic medicine · 2025Review
- Predicting clopidogrel resistance in acute ischemic stroke patients: key clinical insights and a novel diagnostic nomogram.BMC neurology · 2025Article
- Prevalence ofPharmacogenomics and personalized medicine · 2025Article
- Review
- Precision Antiplatelet Therapy after Percutaneous Coronary Intervention (Precision PCI) Registry - Informing optimal antiplatelet strategies.Clinical and translational science · 2024Article
- Pharmacogenomics polygenic risk score: Ready or not for prime time?Clinical and translational science · 2024Review
- Article
- IsGenes · 2024Article
- Effectiveness of Clopidogrel vs Alternative P2YJournal of the American College of Cardiology · 2024Article
- The diversity and clinical implications of genetic variants influencing clopidogrel bioactivation and response in the Emirati population.Human genomics · 2024Article
Corrections and comments
- Erratum issuedCorrigendum.2020
Authors and funding
47 authors.
Funding
Abstract
aimsClopidogrel is prescribed for the prevention of atherothrombotic events. While investigations have identified genetic determinants of inter-individual variability in on-treatment platelet inhibition (e.g. CYP2C19*2), evidence that these variants have clinical utility to predict major adverse cardiovascular events (CVEs) remains controversial. METHODS AND
resultsWe assessed the impact of 31 candidate gene polymorphisms on adenosine diphosphate (ADP)-stimulated platelet reactivity in 3391 clopidogrel-treated coronary artery disease patients of the International Clopidogrel Pharmacogenomics Consortium (ICPC). The influence of these polymorphisms on CVEs was tested in 2134 ICPC patients (N = 129 events) in whom clinical event data were available. Several variants were associated with on-treatment ADP-stimulated platelet reactivity (CYP2C19*2, P = 8.8 × 10-54; CES1 G143E, P = 1.3 × 10-16; CYP2C19*17, P = 9.5 × 10-10; CYP2B6 1294 + 53 C > T, P = 3.0 × 10-4; CYP2B6 516 G > T, P = 1.0 × 10-3; CYP2C9*2, P = 1.2 × 10-3; and CYP2C9*3, P = 1.5 × 10-3). While no individual variant was associated with CVEs, generation of a pharmacogenomic polygenic response score (PgxRS) revealed that patients who carried a greater number of alleles that associated with increased on-treatment platelet reactivity were more likely to experience CVEs (β = 0.17, SE 0.06, P = 0.01) and cardiovascular-related death (β = 0.43, SE 0.16, P = 0.007). Patients who carried eight or more risk alleles were significantly more likely to experience CVEs [odds ratio (OR) = 1.78, 95% confidence interval (CI) 1.14-2.76, P = 0.01] and cardiovascular death (OR = 4.39, 95% CI 1.35-14.27, P = 0.01) compared to patients who carried six or fewer of these alleles.
conclusionSeveral polymorphisms impact clopidogrel response and PgxRS is a predictor of cardiovascular outcomes. Additional investigations that identify novel determinants of clopidogrel response and validating polygenic models may facilitate future precision medicine strategies.
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