Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Meta-Analysis
. 2020 Jun;86(6):1015-1033.
doi: 10.1111/bcp.14247. Epub 2020 Apr 5.

CYP2D6 polymorphism and its impact on the clinical response to metoprolol: A systematic review and meta-analysis

Maxime Meloche  1   2   3 , Michael Khazaka  1   4 , Imad Kassem  1 , Amina Barhdadi  1   2 , Marie-Pierre Dubé  2   3   5 , Simon de Denus  1   2   3
Affiliations
Meta-Analysis

CYP2D6 polymorphism and its impact on the clinical response to metoprolol: A systematic review and meta-analysis

Maxime Meloche et al. Br J Clin Pharmacol. 2020 Jun.

Abstract

Aims: CYP2D6 genetic polymorphisms are associated with metoprolol pharmacokinetics. Whether the clinical response to metoprolol is also affected remains uncertain.

Methods: We conducted a systematic review on the effects of CYP2D6 polymorphism on the clinical response to metoprolol. Searches were conducted using MEDLINE. Meta-analyses were performed on the impact of CYP2D6-inferred phenotypes on heart rate (HR) reduction, diastolic (DBP) and systolic (SBP) blood pressure reduction, average daily doses, all-type adverse events and bradycardia.

Results: Our qualitative assessment indicated inconsistent results in individual studies and endpoints, but CYP2D6 poor metabolizers (PM) generally presented a greater reduction in HR. The meta-analysis of 15 studies, including a total of 1146 individuals, found a reduction in HR of 3 beats/min (P = .017), and of SBP and DBP by 3 mmHg (P = .0048) for PM compared to non-PM individuals using similar metoprolol doses. Bradycardia appeared more frequent by 4-fold for PM, although significant heterogeneity was observed regarding bradycardia, which limits the scope of this finding.

Conclusion: Patients without any CYP2D6 metabolic capacities appear to have increased reduction in DBP, HR and SBP during metoprolol treatment and may be at a higher risk of bradycardia compared to patients with active CYP2D6 phenotypes. Further prospective data are required to determine whether CYP2D6 is associated with clinical events in patients treated with metoprolol, as well as to demonstrate the clinical utility of an individualized approach of prescribing metoprolol using CYP2D6-inferred phenotypes.

Keywords: cytochrome P450 enzymes; genetic polymorphism; meta-analysis; pharmacogenomics; systematic review.

PubMed Disclaimer

Conflict of interest statement

M.‐P.D. is a coauthor on a patent pertaining to pharmacogenomics‐guided CETP inhibition and has minor equity interest in DalCor. M.‐P.D. has received honoraria from Dalcor and research support (access to samples and data) from AstraZeneca, Pfizer, Servier, Sanofi and GlaxoSmithKline. S.D. has received research support through grants from Pfizer, AstraZeneca, Roche Molecular Science, and DalCor.

Figures

Figure 1
Figure 1
Flow chart of the review process
Figure 2
Figure 2
Meta‐analysis of daily drug doses between poor metabolizers (PM) and non‐PM24, 25, 28, 29, 32, 35, 36, 38
Figure 3
Figure 3
Meta‐analysis of reduction in heart rate between poor metabolizers (PM) and non‐PM24, 26, 28, 32, 41
Figure 4
Figure 4
Meta‐analysis of reduction in systolic blood pressure between poor metabolizers (PM) and non‐PM24, 26, 28, 32, 40
Figure 5
Figure 5
Meta‐analysis of reduction in diastolic blood pressure between poor metabolizers (PM) and non‐PM24, 26, 28, 32, 40
Figure 6
Figure 6
Meta‐analysis of all‐type adverse events between poor metabolizers (PM) and non‐PM24, 26, 38
Figure 7
Figure 7
Meta‐analysis of bradycardia between poor metabolizers (PM) and non‐PM24, 26, 28, 36
See this image and copyright information in PMC

References

    1. Zanger UM, Schwab M. Cytochrome P450 enzymes in drug metabolism: regulation of gene expression, enzyme activities, and impact of genetic variation. Pharmacol Ther. 2013;138(1):103‐141. - PubMed
    1. Whirl‐Carrillo M, McDonagh EM, Hebert JM, et al. Pharmacogenomics knowledge for personalized medicine. Clinical Pharmacology & Therapeutics. 2012;92(4):414‐417. - PMC - PubMed
    1. Swen JJ, Nijenhuis M, de Boer A, et al. Pharmacogenetics: from bench to byte‐‐an update of guidelines. Clin Pharmacol Ther. 2011;89(5):662‐673. - PubMed
    1. Crews KR, Gaedigk A, Dunnenberger HM, et al. Clinical Pharmacogenetics implementation consortium guidelines for cytochrome P450 2D6 genotype and codeine therapy: 2014 update. Clin Pharmacol Ther. 2014;95(4):376‐382. - PMC - PubMed
    1. Hicks JK, Bishop JR, Sangkuhl K, et al. Clinical Pharmacogenetics implementation consortium (CPIC) guideline for CYP2D6 and CYP2C19 genotypes and dosing of selective serotonin reuptake inhibitors. Clin Pharmacol Ther. 2015;98(2):127‐134. - PMC - PubMed

Publication types