Pharmacokinetic variability of beta‐adrenergic blocking agents used in cardiology

Ågesen, Frederik Nybye; Weeke, Peter; Tfelt‐Hansen, Peer; Tfelt-Hansen, J; Escape‐Net, for

doi:10.1002/prp2.496

Cited by 35 publications

(29 citation statements)

References 35 publications

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“…However, for LQT2, propranolol might be a relatively better choice. The different efficacies of BBs was primarily due to the pharmacological and pharmacokinetic characteristics of each blocker ( Ågesen et al, 2019 ) ( Figure 6 ). Generally, long-term safety and effectiveness have to be considered for BB treatments in the clinical management of LQTS patients.…”

Section: Discussionmentioning

confidence: 99%

The Efficacy of Beta-Blockers in Patients With Long QT Syndrome 1–3 According to Individuals’ Gender, Age, and QTc Intervals: A Network Meta-analysis

Han

Liu

et al. 2020

Front. Pharmacol.

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Long QT syndrome (LQTS) is an arrhythmic heart disease caused by congenital genetic mutations, and results in increased occurrence rates of polymorphic ventricular tachyarrhythmias and sudden cardiac death (SCD). Clinical evidence from numerous previous studies suggested that beta blockers (BBs), including atenolol, propranolol, metoprolol, and nadolol, exhibit different efficacies for reducing the risk of cardiac events (CEs), such as syncope, arrest cardiac arrest (ACA), and SCD, in patients with LQTS. In this study, we identified relevant studies in MEDLINE, PubMed, embase, and Cochrane databases and performed a meta-analysis to assess the relationship between the rate of CEs and LQTS individuals with confounding variables, including different gender, age, and QTc intervals. Moreover, a network meta-analysis was not only established to evaluate the effectiveness of different BBs, but also to provide the ranked efficacies of BBs treatment for preventing the recurrence of CEs in LQT1 and LQT2 patients. In conclusion, nadolol was recommended as a relatively effective strategy for LQT2 in order to improve the prognosis of patients during a long follow-up period.

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Section: Discussionmentioning

confidence: 99%

The Efficacy of Beta-Blockers in Patients With Long QT Syndrome 1–3 According to Individuals’ Gender, Age, and QTc Intervals: A Network Meta-analysis

Han

Liu

et al. 2020

Front. Pharmacol.

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“…However, a further analysis according to the type of beta-blocker used was only performed in the study by McCourt et al, which showed no impact on MSS [26]. A recent review study conducted by Ågesen et al [27] tried to define the individual bioavailability of beta-blockers used in cardiology. A significant variation has been shown and this may be a confounding factor when trying to investigate the effect of the drugs in cancer patients, since dose adjustments and the timing of the treatment could be crucial when evaluating a possible favorable effect.…”

Section: Discussionmentioning

confidence: 99%

The Effect of Beta-Adrenergic Blocking Agents in Cutaneous Melanoma—A Nation-Wide Swedish Population-Based Retrospective Register Study

Katsarelias

Eriksson

Mikiver

et al. 2020

Cancers

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Previous studies have demonstrated an anti-tumoral effect of beta-adrenergic blocking agents on cutaneous melanoma (CM). The aim of this study was to investigate if beta-adrenergic blocking agents have an impact on survival in Swedish patients with melanoma. A population-based retrospective registry study including all patients diagnosed with a primary invasive melanoma between 2009 and 2013 was performed. Data from the Swedish Melanoma Register were linked to the Swedish Prescribed Drug Registry and the Swedish Cause of Death Register. Cox regression analyses including competing risk assessments were performed. There were 12,738 patients included, out of which 3702 were exposed to beta-blockers vs. 9036 non-exposed patients. Age, male sex, Breslow thickness, ulceration, and nodal status were independent negative prognostic factors for melanoma-specific survival (MSS). Adding beta-blockers to the analysis did not add any prognostic value to the model (HR 1.00, p = 0.98), neither when adjusting for competing risks (HR 0.97, p = 0.61). When specifically analyzing the use of non-selective beta-blockers, the results were still without statistical significance (HR 0.76, p = 0.21). In conclusion, this population-based registry study could not verify that the use of beta-adrenergic blocking agents improve survival in patients with melanoma.

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“…We included all Medi‐Cal beneficiaries older than 18 years of age who were continuously enrolled in the FFS program for a minimum of 12 months and were initiated on a β‐blocker undergoing CYP2D6 metabolism as a primary route of elimination (metoprolol, propranolol, labetalol, carvedilol, or nebivolol) between January 1, 2004, and December 31, 2011 20–25 . For those patients who were also prescribed an antidepressant subsequent to the β‐blocker prescription, we required continuous enrollment in the FFS program for at least 12 months before the initial prescription for the antidepressant medication and 2 months immediately after the initial antidepressant prescription.…”

Section: Methodsmentioning

confidence: 99%

Combining Antidepressants with β‐Blockers: Evidence of a Clinically Significant CYP2D6 Drug Interaction

2020

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BACKGROUND The b-blockers and antidepressants are two of the most commonly prescribed drug classes in the United States. Several antidepressants are potent inhibitors of cytochrome P450 2D6 liver enzymes (CYP2D6) and can increase the plasma concentrations of certain b-blockers when administered concomitantly, potentially leading to serious medical consequences such as hypotension, bradycardia, and falls. OBJECTIVE The primary objective of this investigation was to determine whether initiating an antidepressant in patients receiving b-blockers increased the risk of hemodynamic adverse events. Our primary outcome was time to hospital admissions or emergency department (ED) visits for an International Classification of Diseases-9 diagnosis suggestive of excessive b-blockade. METHODS We conducted a survival analysis for adults continuously enrolled in the California Medicaid system (Medi-Cal) between 2004 and 2012. Eligible patients were required to be receiving b-blocker medications that are primarily CYP2D6 substrates (e.g., metoprolol, propranolol, or carvedilol). Univariate and multivariable analyses were performed for patients who concurrently received antidepressants with b-blockers. An additional multivariable analysis analyzed the association of this combination upon hospitalizations or ED visits for all causes. RESULTS A total of 21,292 beneficiaries met the inclusion criteria, and 4.3% of patients required hospitalization or ED visits within 30 days of co-medication. In multivariable analysis, patients receiving antidepressants with moderate to strong CYP2D6 inhibitory potential (fluoxetine, paroxetine, duloxetine, or bupropion) had a greater risk for hospitalization or ED visits for hemodynamic events than those initiated on antidepressants with weak CYP2D6 inhibition for 30 days or less when each was compared with patients receiving no antidepressants (hazard ratio [HR] 1.53, 95% confidence interval [CI] 1.03-2.81; p=0.04 vs HR 1.24; 95% CI 0.82-1.88; p=0.30). Other demographic variables associated with increased morbidity included advanced age, male sex, higher b-blocker doses, and African American race or Hispanic ethnicity. CONCLUSIONS Results of this analysis suggest that initiation of certain antidepressants was associated with an increased risk for serious medical sequelae among patients concurrently receiving b-blockers. Greater risk was observed with antidepressants that potently inhibit the CYP2D6 enzyme, implying that increased morbidity may be mediated by a metabolic drug interaction. KEY WORDS b-blockers, antidepressants, drug interactions, cytochrome P450 2D6, pharmacoepidemiology.

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Pharmacokinetic variability of beta‐adrenergic blocking agents used in cardiology

Cited by 35 publications

References 35 publications

The Efficacy of Beta-Blockers in Patients With Long QT Syndrome 1–3 According to Individuals’ Gender, Age, and QTc Intervals: A Network Meta-analysis

The Efficacy of Beta-Blockers in Patients With Long QT Syndrome 1–3 According to Individuals’ Gender, Age, and QTc Intervals: A Network Meta-analysis

The Effect of Beta-Adrenergic Blocking Agents in Cutaneous Melanoma—A Nation-Wide Swedish Population-Based Retrospective Register Study

Combining Antidepressants with β‐Blockers: Evidence of a Clinically Significant CYP2D6 Drug Interaction

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