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Impact of the CYP2D6 Genotype on Metoprolol Tolerance and Adverse Events in Elderly Chinese Patients With Cardiovascular Diseases

The latest consensus has changed CYP2D6 genotyping among Chinese population, while its impact on metoprolol tolerance and adverse events in elderly Chinese patients with cardiovascular diseases remains unclear. In this study, we prospectively included elderly patients who started metoprolol treatmen...

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Autores principales: Chen, Jianqiao, Zheng, Jin, Zhu, Zifan, Hao, Benchuan, Wang, Miao, Li, Huiying, Cai, Yulun, Wang, Shiqi, Li, Jun, Liu, Hongbin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9019718/
https://www.ncbi.nlm.nih.gov/pubmed/35462926
http://dx.doi.org/10.3389/fphar.2022.876392
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author Chen, Jianqiao
Zheng, Jin
Zhu, Zifan
Hao, Benchuan
Wang, Miao
Li, Huiying
Cai, Yulun
Wang, Shiqi
Li, Jun
Liu, Hongbin
author_facet Chen, Jianqiao
Zheng, Jin
Zhu, Zifan
Hao, Benchuan
Wang, Miao
Li, Huiying
Cai, Yulun
Wang, Shiqi
Li, Jun
Liu, Hongbin
author_sort Chen, Jianqiao
collection PubMed
description The latest consensus has changed CYP2D6 genotyping among Chinese population, while its impact on metoprolol tolerance and adverse events in elderly Chinese patients with cardiovascular diseases remains unclear. In this study, we prospectively included elderly patients who started metoprolol treatment for cardiovascular indications. According to the latest consensus on CYP2D6 genotype-to-phenotype translation, the patients were categorized as normal, intermediate, or poor metabolizers (NMs, IMs, or PMs, respectively) by detecting the presence of the CYP2D6*1, *2, *5, *10, and *14. Logistic regression model was used to analyze the correlation between the CYP2D6 phenotype and incidence of adverse events, which were assessed over a 12-week period. In this study, there were 651 (62.7%) NMs, 385 (37.1%) IMs, and 3 (0.3%) PMs. After 12 weeks of follow-up, compared with NMs, IMs had the lower maintenance dose [50.0 (25.0–50.0) mg/day vs. 25.0 (25.0–50.0) mg/day, p < 0.001] and lower weight-adjusted maintenance doses (0.52 ± 0.25 mg/day/kg vs. 0.42 ± 0.22 mg/day/kg, p < 0.001), and had higher incidence of postural hypotension (6.0% vs. 10.9%, p = 0.006), bradycardia (21.5% vs. 28.6%, p = 0.011), asystole (0.8% vs. 3.1%, p = 0.009) and syncope (2.0% vs. 6.2%, p = 0.001). In logistic regression model, the overall incidence of adverse events was 1.37-fold larger in IMs than in NMs (odds ratio = 1.37, 95% confidence interval = 1.05–1.79, p = 0.021). We conclude that IMs have lower tolerance and higher incidence of metoprolol-related adverse events than NMs in elderly Chinese patients with cardiovascular diseases. CYP2D6 genotyping is justifiable in elderly patients to minimize the risk of adverse events and ensure the benefits of metoprolol.
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spelling pubmed-90197182022-04-21 Impact of the CYP2D6 Genotype on Metoprolol Tolerance and Adverse Events in Elderly Chinese Patients With Cardiovascular Diseases Chen, Jianqiao Zheng, Jin Zhu, Zifan Hao, Benchuan Wang, Miao Li, Huiying Cai, Yulun Wang, Shiqi Li, Jun Liu, Hongbin Front Pharmacol Pharmacology The latest consensus has changed CYP2D6 genotyping among Chinese population, while its impact on metoprolol tolerance and adverse events in elderly Chinese patients with cardiovascular diseases remains unclear. In this study, we prospectively included elderly patients who started metoprolol treatment for cardiovascular indications. According to the latest consensus on CYP2D6 genotype-to-phenotype translation, the patients were categorized as normal, intermediate, or poor metabolizers (NMs, IMs, or PMs, respectively) by detecting the presence of the CYP2D6*1, *2, *5, *10, and *14. Logistic regression model was used to analyze the correlation between the CYP2D6 phenotype and incidence of adverse events, which were assessed over a 12-week period. In this study, there were 651 (62.7%) NMs, 385 (37.1%) IMs, and 3 (0.3%) PMs. After 12 weeks of follow-up, compared with NMs, IMs had the lower maintenance dose [50.0 (25.0–50.0) mg/day vs. 25.0 (25.0–50.0) mg/day, p < 0.001] and lower weight-adjusted maintenance doses (0.52 ± 0.25 mg/day/kg vs. 0.42 ± 0.22 mg/day/kg, p < 0.001), and had higher incidence of postural hypotension (6.0% vs. 10.9%, p = 0.006), bradycardia (21.5% vs. 28.6%, p = 0.011), asystole (0.8% vs. 3.1%, p = 0.009) and syncope (2.0% vs. 6.2%, p = 0.001). In logistic regression model, the overall incidence of adverse events was 1.37-fold larger in IMs than in NMs (odds ratio = 1.37, 95% confidence interval = 1.05–1.79, p = 0.021). We conclude that IMs have lower tolerance and higher incidence of metoprolol-related adverse events than NMs in elderly Chinese patients with cardiovascular diseases. CYP2D6 genotyping is justifiable in elderly patients to minimize the risk of adverse events and ensure the benefits of metoprolol. Frontiers Media S.A. 2022-04-06 /pmc/articles/PMC9019718/ /pubmed/35462926 http://dx.doi.org/10.3389/fphar.2022.876392 Text en Copyright © 2022 Chen, Zheng, Zhu, Hao, Wang, Li, Cai, Wang, Li and Liu. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Chen, Jianqiao
Zheng, Jin
Zhu, Zifan
Hao, Benchuan
Wang, Miao
Li, Huiying
Cai, Yulun
Wang, Shiqi
Li, Jun
Liu, Hongbin
Impact of the CYP2D6 Genotype on Metoprolol Tolerance and Adverse Events in Elderly Chinese Patients With Cardiovascular Diseases
title Impact of the CYP2D6 Genotype on Metoprolol Tolerance and Adverse Events in Elderly Chinese Patients With Cardiovascular Diseases
title_full Impact of the CYP2D6 Genotype on Metoprolol Tolerance and Adverse Events in Elderly Chinese Patients With Cardiovascular Diseases
title_fullStr Impact of the CYP2D6 Genotype on Metoprolol Tolerance and Adverse Events in Elderly Chinese Patients With Cardiovascular Diseases
title_full_unstemmed Impact of the CYP2D6 Genotype on Metoprolol Tolerance and Adverse Events in Elderly Chinese Patients With Cardiovascular Diseases
title_short Impact of the CYP2D6 Genotype on Metoprolol Tolerance and Adverse Events in Elderly Chinese Patients With Cardiovascular Diseases
title_sort impact of the cyp2d6 genotype on metoprolol tolerance and adverse events in elderly chinese patients with cardiovascular diseases
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9019718/
https://www.ncbi.nlm.nih.gov/pubmed/35462926
http://dx.doi.org/10.3389/fphar.2022.876392
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