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Precision medicine in cardiovascular therapeutics: Evaluating the role of pharmacogenetic analysis prior to drug treatment

Journal of internal medicine, 2024-05, Vol.295 (5), p.583-598 [Peer Reviewed Journal]

2024 The Authors. Journal of Internal Medicine published by John Wiley & Sons Ltd on behalf of Association for Publication of The Journal of Internal Medicine. ;2024. This article is published under http://creativecommons.org/licenses/by-nc-nd/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. ;ISSN: 0954-6820 ;ISSN: 1365-2796 ;EISSN: 1365-2796 ;DOI: 10.1111/joim.13772 ;PMID: 38343077

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Title:
Precision medicine in cardiovascular therapeutics: Evaluating the role of pharmacogenetic analysis prior to drug treatment
Author: Ingelman-Sundberg, Magnus ; Pirmohamed, Munir
Subjects: Anticoagulants ; Anticoagulants - therapeutic use ; Cardiomyopathy ; Cardiovascular disease ; Cardiovascular diseases ; Cardiovascular Diseases - diagnosis ; Cardiovascular Diseases - drug therapy ; Cardiovascular Diseases - genetics ; Chemical kinetics ; Clopidogrel ; Clopidogrel - therapeutic use ; Cost benefit analysis ; Cytochrome P-450 CYP2C19 - genetics ; Cytochrome P-450 CYP2C19 - therapeutic use ; Drug metabolism ; Drug therapy ; Drugs ; Economic analysis ; Effectiveness ; Gene sequencing ; Genetic diversity ; Genetic variation ; Genomes ; Genotyping ; Health services ; Heritability ; Humans ; Liver-Specific Organic Anion Transporter 1 - genetics ; Medicin och hälsovetenskap ; Metabolism ; Pharmacogenetics ; Pharmacogenomic Testing ; Pharmacogenomics ; Pharmacokinetics ; Phenotypes ; Polymorphism ; Precision Medicine ; Safety ; Simvastatin ; Statins ; Vitamin K Epoxide Reductases - genetics ; Warfarin ; Warfarin - therapeutic use ; Whole genome sequencing
Is Part Of: Journal of internal medicine, 2024-05, Vol.295 (5), p.583-598
Description: Pharmacogenomics is the examination of how genetic variation influences drug metabolism and response, in terms of both efficacy and safety. In cardiovascular disease, patient-specific diplotypes determine phenotypes, thereby influencing the efficacy and safety of drug treatments, including statins, antiarrhythmics, anticoagulants and antiplatelets. Notably, polymorphisms in key genes, such as CYP2C9, CYP2C19, VKORC1 and SLCO1B1, significantly impact the outcomes of treatment with clopidogrel, warfarin and simvastatin. Furthermore, the CYP2C19 polymorphism influences the pharmacokinetics and safety of the novel hypertrophic cardiomyopathy inhibitor, mavacamten. In this review, we critically assess the clinical application of pharmacogenomics in cardiovascular disease and delineate present and future utilization of pharmacogenomics. This includes insights into identifying missing heritability, the integration of whole genome sequencing and the application of polygenic risk scores to enhance the precision of personalized drug therapy. Our discussion encompasses health economic analyses that underscore the cost benefits associated with pre-emptive genotyping for warfarin and clopidogrel treatments, albeit acknowledging the need for further research in this area. In summary, we contend that cardiovascular pharmacogenomic analyses are underpinned by a wealth of evidence, and implementation is already occurring for some of these gene-drug pairs, but as with any area of medicine, we need to continually gather more information to optimize the use of pharmacogenomics in clinical practice.
Publisher: England: Blackwell Publishing Ltd
Language: English
Identifier: ISSN: 0954-6820
ISSN: 1365-2796
EISSN: 1365-2796
DOI: 10.1111/joim.13772
PMID: 38343077
Source: SWEPUB Freely available online

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Precision medicine in cardiovascular therapeutics: Evaluating the role of pharmacogenetic analysis prior to drug treatment

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