Pharmacogenetics to guide cardiovascular drug therapy

Duarte, Julio D.; Cavallari, Larisa H.

doi:10.1038/s41569-021-00549-w

Cited by 65 publications

(39 citation statements)

References 213 publications

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“… 7 Real-world data has shown that the risks were most pronounced in patients with the acute coronary syndrome. 6 Therefore, early intervention after PCI appears to be beneficial for acute coronary syndrome patients with the CYP2C19 phenotype.…”

Section: Introductionmentioning

confidence: 99%

Clopidogrel Use and CYP2C19 Genotypes in Patients Undergoing Vascular Intervention Procedure: A Hospital-Based Study

Liao¹,

Hsiao²,

Lin³

et al. 2022

PGPM

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Purpose Clopidogrel is widely used in coronary artery, peripheral arterial, and cerebrovascular disease. We aimed to study the association of the CYP2C19 phenotype with cardiovascular outcomes and interventional procedures in a hospital-based population. Patients and Methods This cross-sectional, retrospective study enrolled patients with prior exposure to clopidogrel at the Taichung Veterans General Hospital (TCVGH) using data extracted from the Taiwan Precision Medicine Initiative (TPMI). Data on the CYP2C19 phenotype, drug-prescription profile, comorbidities, vascular intervention procedures, and hospitalization due to acute myocardial infarction (AMI) or stroke of clopidogrel users were analyzed. Results From the 32,728 patients in the TCVGH-TPMI cohort, we selected 2687 clopidogrel users. A total of 400 (14.9%) clopidogrel poor metabolizers (PMs), 1235 (46.0%) intermediate metabolizers (IMs), and 1052 (39.2%) extensive metabolizers (EMs) were identified. The predominant loss-of-function allele is *2. In 2687 patients with clopidogrel exposure, the CYP2C19 PM phenotype was unassociated with hospitalization due to AMI or stroke after adjusting for comorbidities and carotid angiographies. Among the 1554 clopidogrel users who underwent cardiovascular intervention, 193 (12.4%) received two or more types of interventional procedures. Compared with non-PMs, patients with the PM phenotype had a higher risk of multiple carotid interventions (OR: 3.13, 95% CI: 1.19–8.22). Conclusion In this hospital-wide cohort, 8.2% were clopidogrel users, of which 14.9% were CYP2C19 PMs. The result of this study does not support universal genotyping of CYP2C19 in all clopidogrel users to identify risks for stroke and AMI. CYP2C19 PMs are more likely to undergo multiple carotid interventions than non-PMs. Prospective studies to investigate the association of the CYP2C19 genotype and carotid interventions and outcomes are needed to validate our results.

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Section: Introductionmentioning

confidence: 99%

Clopidogrel Use and CYP2C19 Genotypes in Patients Undergoing Vascular Intervention Procedure: A Hospital-Based Study

Liao¹,

Hsiao²,

Lin³

et al. 2022

PGPM

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“…Medical care could be significantly improved through genetic data sharing between research centers and pharmaceutical companies [20]. Genomic data exchange is needed for the development and improvement of precise medicine strategies, with an exponential number of investigational drug trials requiring genotype information for patient selection [21][22][23][24]. Hence, the dilemma of genetic data sharing and its potential abuse must carefully and continuously be balanced [25][26][27].…”

Section: Introductionmentioning

confidence: 99%

Controlling my genome with my smartphone: first clinical experiences of the PROMISE system

et al. 2021

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Background The development of Precision Medicine strategies requires high-dimensional phenotypic and genomic data, both of which are highly privacy-sensitive data types. Conventional data management systems lack the capabilities to sufficiently handle the expected large quantities of such sensitive data in a secure manner. PROMISE is a genetic data management concept that implements a highly secure platform for data exchange while preserving patient interests, privacy, and autonomy. Methods The concept of PROMISE to democratize genetic data was developed by an interdisciplinary team. It integrates a sophisticated cryptographic concept that allows only the patient to grant selective access to defined parts of his genetic information with single DNA base-pair resolution cryptography. The PROMISE system was developed for research purposes to evaluate the concept in a pilot study with nineteen cardiomyopathy patients undergoing genotyping, questionnaires, and longitudinal follow-up. Results The safety of genetic data was very important to 79%, and patients generally regarded the data as highly sensitive. More than half the patients reported that their attitude towards the handling of genetic data has changed after using the PROMISE app for 4 months (median). The patients reported higher confidence in data security and willingness to share their data with commercial third parties, including pharmaceutical companies (increase from 5 to 32%). Conclusion PROMISE democratizes genomic data by a transparent, secure, and patient-centric approach. This clinical pilot study evaluating a genetic data infrastructure is unique and shows that patient’s acceptance of data sharing can be increased by patient-centric decision-making. Graphic abstract

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“…Reviewing the evidence supporting pharmacogenetic testing in cardiovascular medicine including available clinical trials that constitute the basis for the recommendations included in these guidelines falls beyond the scope of this article. An excellent review on this issue has been recently published by Duarte et al [11].…”

Section: Introductionmentioning

confidence: 99%

Pharmacogenetics to Avoid Adverse Reactions in Cardiology: Ready for Implementation?

García-González¹,

Salvador-Martín²

2021

JPM

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Cardiovascular Diseases (CVs) are one of the main causes of mortality and disability around the world. Advances in drug treatment have greatly improved survival and quality of life in the past decades, but associated adverse events remain a relevant problem. Pharmacogenetics can help individualize cardiovascular treatment, reducing associated toxicities and improving outcomes. Several scientific societies and working groups periodically review available studies and provide consensus recommendations for those gene-drug pairs with a sufficient level of evidence. However, these recommendations are rarely mandatory, and the indications on how to adjust treatment can vary between different guidelines, which limits their clinical applicability. The aim of this review is to compile, compare and discuss available guidelines and recommendations by the main Pharmacogenetics Consortiums (Clinical Pharmacogenetics Implementation Consortium (CPIC); Dutch Pharmacogenetics Working Group (DPWG); the French Network of Pharmacogenetics (Réseau national de pharmacogénétique (RNPGx) and The Canadian Pharmacogenomics Network for Drug Safety (CPNDS) regarding how to apply pharmacogenetic results to optimize pharmacotherapy in cardiology. Pharmacogenetic recommendations included in European or American drug labels, as well as those included in the European Society of Cardiology (ESC) and the American College of Cardiology (ACC) and the American Heart Association (AHA) treatment guidelines are also discussed.

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Pharmacogenetics to guide cardiovascular drug therapy

Cited by 65 publications

References 213 publications

Clopidogrel Use and CYP2C19 Genotypes in Patients Undergoing Vascular Intervention Procedure: A Hospital-Based Study

Clopidogrel Use and CYP2C19 Genotypes in Patients Undergoing Vascular Intervention Procedure: A Hospital-Based Study

Controlling my genome with my smartphone: first clinical experiences of the PROMISE system

Pharmacogenetics to Avoid Adverse Reactions in Cardiology: Ready for Implementation?

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