Impact of genotype-predicted CYP2D6 metabolism on clinical effects and tolerability of metoprolol in patients after myocardial infarction – a prospective observational study

Anstensrud, Anne Kristine; Molden, Espen; Haug, Hans Jørgen; Qazi, Rehman; Muriq, Hysen; Fosshaug, Linn E.; Spigset, Olav; Øie, Erik

doi:10.1007/s00228-020-02832-0

Cited by 12 publications

(12 citation statements)

References 25 publications

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“…No association between CYP2D6 and systolic blood pressure in metoprolol users has been identified 96,98,101,103 . However, at least three studies, including the two largest to date have linked CYP2D6 PM status to a ~5 mmHg reduction in diastolic blood pressure relative to EMs, although this has not been replicated in all studies 96,98,99,[101][102][103]105 . Bar an early small case-control study, clinically apparent adverse events have not been associated with CYP2D6 PMs or IMs 98,99,101,102,[105][106][107] .…”

Section: Beta-blockersmentioning

confidence: 99%

“…However, at least three studies, including the two largest to date have linked CYP2D6 PM status to a ~5 mmHg reduction in diastolic blood pressure relative to EMs, although this has not been replicated in all studies 96,98,99,[101][102][103]105 . Bar an early small case-control study, clinically apparent adverse events have not been associated with CYP2D6 PMs or IMs 98,99,101,102,[105][106][107] . One limitation of some of these studies is a reliance on a single, albeit common, loss-of-function variant, CYP2D6*4 (rs3892097) for assigning CYP2D6 predicted function 96,97,101 .…”

Section: Beta-blockersmentioning

confidence: 99%

“…Several studies have investigated the clinical effects of CYP2D6 in patients taking metoprolol, mostly for heart failure (HF) or hypertension (HTN). The tolerated maintenance metoprolol dose in CYP2D6 poor metabolisers (PMs) relative to extensive (normal) metabolisers (EMs) is lower in some, but not all studies [96][97][98][99][100][101] . A decreased heart rate (HR) has been frequently reported in intermediate metabolisers (IMs) and particularly PMs relative to EMs, and an increased incidence of (mostly asymptomatic) bradycardia (HR<60bpm) has been reported in CYP2D6 PMs and occasionally IMs in some but not all studies 96,98,99,[101][102][103][104] .…”

Section: Beta-blockersmentioning

confidence: 99%

“…The tolerated maintenance metoprolol dose in CYP2D6 poor metabolisers (PMs) relative to extensive (normal) metabolisers (EMs) is lower in some, but not all studies [96][97][98][99][100][101] . A decreased heart rate (HR) has been frequently reported in intermediate metabolisers (IMs) and particularly PMs relative to EMs, and an increased incidence of (mostly asymptomatic) bradycardia (HR<60bpm) has been reported in CYP2D6 PMs and occasionally IMs in some but not all studies 96,98,99,[101][102][103][104] . No association between CYP2D6 and systolic blood pressure in metoprolol users has been identified 96,98,101,103 .…”

Section: Beta-blockersmentioning

confidence: 99%

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The role of pharmacogenomics in contemporary cardiovascular therapy: a position statement from the European Society of Cardiology Working Group on Cardiovascular Pharmacotherapy

Magavern

Kaski

Turner

et al. 2021

European Heart Journal - Cardiovascular Pharmacotherapy

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There is a strong and ever-growing body of evidence regarding the use of pharmacogenomics to inform cardiovascular pharmacology. However, there is no common position taken by international cardiovascular societies to unite diverse availability, interpretation and application of such data, nor is there recognition of the challenges of variation in clinical practice between countries within Europe. Aside from the considerable barriers to implementing pharmacogenomic testing and the complexities of clinically actioning results, there are differences in the availability of resources and expertise internationally within Europe. Diverse legal and ethical approaches to genomic testing and clinical therapeutic application also require serious thought. As direct-to-consumer genomic testing becomes more common, it can be anticipated that data may be brought in by patients themselves, which will require critical assessment by the clinical cardiovascular prescriber. In a modern, pluralistic and multi-ethnic Europe, self-identified race/ethnicity may not be concordant with genetically detected ancestry and thus may not accurately convey polymorphism prevalence. Given the broad relevance of pharmacogenomics to areas such as thrombosis and coagulation, interventional cardiology, heart failure, arrhythmias, clinical trials, and policy/regulatory activity within cardiovascular medicine, as well as to genomic and pharmacology subspecialists, this position statement attempts to address these issues at a wide-ranging level.

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Section: Beta-blockersmentioning

confidence: 99%

Section: Beta-blockersmentioning

confidence: 99%

Section: Beta-blockersmentioning

confidence: 99%

Section: Beta-blockersmentioning

confidence: 99%

See 2 more Smart Citations

The role of pharmacogenomics in contemporary cardiovascular therapy: a position statement from the European Society of Cardiology Working Group on Cardiovascular Pharmacotherapy

Magavern

Kaski

Turner

et al. 2021

European Heart Journal - Cardiovascular Pharmacotherapy

View full text Add to dashboard Cite

show abstract

“…It has been reported that due to increased metoprolol concentrations, CYP2D6 IM and especially PM experience lower heart rates and an increased incidence of bradycardia [77][78][79]. However, this does not seem to relevantly impact drug safety and tolerability in most cases.…”

Section: • Metoprolol and Cyp2d6mentioning

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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Co-prescription of metoprolol and CYP2D6-inhibiting antidepressants before and after implementation of an optimized drug interaction database in Norway

Gedde-Dahl

Spigset

Molden

2022

Eur J Clin Pharmacol

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Purpose To compare the co-prescription of metoprolol and potent CYP2D6-inhibiting antidepressants before and during a 10-year period after implementation of an optimized drug interaction database into clinical decision support systems in Norway. Methods The study was a retrospective, cross-sequential nationwide analysis of drug-dispensing data retrieved from the Norwegian Prescription Database over a 1-year period before (2007) and two 1-year periods after (2012 and 2017) implementation of a drug interaction database providing recommendations on non-interacting alternative medications. Primary outcome was changes in co-prescription rates of metoprolol and the potent CYP2D6-inhibiting antidepressants fluoxetine, paroxetine, or bupropion relative to alternative antidepressants with no or limited CYP2D6 inhibitory potential. To control for potential secular trend bias, a comparison group consisting of atenolol/bisoprolol users was included. Results The co-prescription rate of metoprolol with potent CYP2D6 inhibitors declined following implementation of the optimized database, by 21% (P < 0.001) after 5 years and by 40% (P < 0.001) after 10 years. Compared with atenolol/bisoprolol users, patients treated with metoprolol had significantly reduced likelihood of being prescribed a CYP2D6-inhibiting antidepressant in the two post-implementation periods (OR 0.61 (95% CI 0.54–0.69) and OR 0.45 (95% CI 0.40–0.51), respectively, versus OR 0.84 (95% CI 0.74–0.94) prior to implementation). Small and mostly insignificant differences in average daily metoprolol dosage were found between patients treated with the various antidepressants. Conclusion The present study suggests that implementation of a drug interaction database providing recommendations on non-interacting drug alternatives contributes to reduced co-prescribing of drug combinations associated with potentially serious adverse effects.

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Impact of genotype-predicted CYP2D6 metabolism on clinical effects and tolerability of metoprolol in patients after myocardial infarction – a prospective observational study

Cited by 12 publications

References 25 publications

The role of pharmacogenomics in contemporary cardiovascular therapy: a position statement from the European Society of Cardiology Working Group on Cardiovascular Pharmacotherapy

The role of pharmacogenomics in contemporary cardiovascular therapy: a position statement from the European Society of Cardiology Working Group on Cardiovascular Pharmacotherapy

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

Co-prescription of metoprolol and CYP2D6-inhibiting antidepressants before and after implementation of an optimized drug interaction database in Norway

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