Aldosterone Pathway Blockade to Prevent Atrial Fibrillation: A Systematic Review and Meta-Analysis

Neefs, Jolien; Berg, Nicoline W. E. van den; Limpens, Jacqueline; Berger, Wouter R.; Boekholdt, S. Matthijs; Sanders, Prashanthan; Groot, Joris R. de

doi:10.1016/j.ijcard.2016.12.029

Cited by 83 publications

(46 citation statements)

References 34 publications

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“…15 In a meta-analysis of 5 randomized controlled trials and 9 observational cohorts (included 5332 patients), use of MRA reduced AF occurrence: 8.5% versus 18.6%, driven by a reduction in both new-onset and recurrent AF. 65 The conclusions are consistent with another meta-analysis, which also where benefits of MRAs were evident in heart failure settings. 66 The capacity of an MRA, spironolactone to improve exercise tolerance, quality of life, and diastolic function specifically in patients with AF is being tested the ongoing randomized controlled IMPRESS-AF trial (Improved Exercise Tolerance in Heart Failure With Preserved Ejection Fraction by Spironolactone on Myocardial Fibrosis in Atrial Fibrillation, NCT02673463).…”

Section: Mineralocorticoid Receptor Antagonists In Hypertension and Afsupporting

confidence: 87%

Atrial Fibrillation and Hypertension

et al. 2017

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Section: Mineralocorticoid Receptor Antagonists In Hypertension and Afsupporting

confidence: 87%

Atrial Fibrillation and Hypertension

et al. 2017

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“…Consequently, aldosterone pathway blockade by mineralocorticoid receptor antagonists (MRAs), such as spironolactone and eplerenone, may reduce HF symptoms and the risk of AF. MRAs were found to be effective in reducing new-onset AF or recurrence of pre-existent AF in patients with HF, not further specified [7]. Moreover, a secondary analysis of the EMPHASIS-HF (Eplerenone in Mild Patients Hospitalization And SurvIval Study in Heart Failure) trial, which included only patients with HF with a…”

Section: Introductionmentioning

confidence: 99%

Effect of Spironolactone on Atrial Fibrillation in Patients with Heart Failure with Preserved Ejection Fraction: Post-Hoc Analysis of the Randomized, Placebo-Controlled TOPCAT Trial

Neefs

Berg

Krul

et al. 2019

Am J Cardiovasc Drugs

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Background Mineralocorticoid receptor antagonists (MRAs) reduce the risk of atrial fibrillation (AF) in patients with heart failure (HF) and a reduced ejection fraction. The efficacy of MRAs for AF prevention in patients with HF and a preserved ejection fraction (HFpEF) is unclear. Objectives We performed a secondary analysis of a randomized placebo-controlled trial to determine the efficacy of spironolactone in reducing new-onset AF and recurrence of AF in 2733 patients with symptomatic HFpEF. Methods Patients with and without prevalent AF at baseline were included, and those with permanent AF were excluded. Patients were randomized 1:1 to spironolactone or placebo. The risk of new-onset AF or the recurrence of AF was quantified using hazard ratios (HRs) with corresponding 95% confidence intervals (CIs). Results At baseline, 2228 (64.7%) patients had no history of AF (spironolactone, n = 1111; placebo, n = 1117), whereas 505 (18.4%) patients had prevalent AF (spironolactone, n = 260; placebo, n = 245). During a median follow-up of 3.1 years (interquartile range [IQR] 2.0-4.9), the incidence of new-onset AF was similar in both treatment arms: spironolactone 5.2% (n = 58) versus placebo 4.4% (n = 49); p = 0.41. The risk of new-onset AF was similar in both treatment arms: HR 1.19; 95% CI 0.81-1.74; p = 0.38. AF recurrence was also similar in both treatment arms during a median follow-up of 3.3 years (IQR 1.9-4.7): spironolactone 11.5% (n = 30) versus placebo 11.8% (n = 29); p = 1.00. The risk of recurrence of AF did not differ per treatment arm: HR 0.94; 95% CI 0.57-1.58; p = 0.83. Conclusion Spironolactone does not reduce the risk of new-onset AF or AF recurrence in patients with HFpEF. This is in contrast to results in cohorts of patients with HF and a reduced ejection fraction. Clinical trial registration ClinicalTrials.gov identifier no. NCT00094302 (TOPCAT).

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“…The investigators observed a significant reduction of new onset AF in the group randomized to EPL (2.7% vs. 4.5%) (Zannad et al, 2011). These data are supported by a recent meta-analysis that included 14 studies (five randomized clinical trials and nine observational studies) and 5332 patients, of whom 2397 received MRBs (EPL or spironolactone), which showed that the incidence of AF in this group was significantly lower compared with patients who did not receive this treatment (8.5% and 18.6%, respectively) (Neefs et al, 2017). Although the specific mechanism of action was not an objective of the work, the inhibition of fibrosis and atrial structural remodeling might be highly involved, as has been demonstrated in the animal model of persistent AF in sheep, with high similarity to clinical AF (Takemoto et al, 2016).…”

Section: B Remodeling and Upstream Therapies In Atrial Fibrillationmentioning

confidence: 54%

Mechanisms and Drug Development in Atrial Fibrillation

2018

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Atrial fibrillation is a highly prevalent cardiac arrhythmia and the most important cause of embolic stroke. Although genetic studies have identified an increasing assembly of AF-related genes, the impact of these genetic discoveries is yet to be realized. In addition, despite more than a century of research and speculation, the molecular and cellular mechanisms underlying AF have not been established, and therapy for AF, particularly persistent AF, remains suboptimal. Current antiarrhythmic drugs are associated with a significant rate of adverse events, particularly proarrhythmia, which may explain why many highly symptomatic AF patients are not receiving any rhythm control therapy. This review focuses on recent advances in AF research, including its epidemiology, genetics, and pathophysiological mechanisms. We then discuss the status of antiarrhythmic drug therapy for AF today, reviewing molecular mechanisms, and the possible clinical use of some of the new atrial-selective antifibrillatory agents, as well as drugs that target atrial remodeling, inflammation and fibrosis, which are being tested as upstream therapies to prevent AF perpetuation. Altogether, the objective is to highlight the magnitude and endemic dimension of AF, which requires a significant effort to develop new and effective antiarrhythmic drugs, but also improve AF prevention and treatment of risk factors that are associated with AF complications.

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Aldosterone Pathway Blockade to Prevent Atrial Fibrillation: A Systematic Review and Meta-Analysis

Abstract: MRAs significantly reduce new-onset AF and recurrent AF, but not POAF. MRA treatment can be considered an additive therapeutic strategy in AF.

Cited by 83 publications

References 34 publications

Atrial Fibrillation and Hypertension

Atrial Fibrillation and Hypertension

Effect of Spironolactone on Atrial Fibrillation in Patients with Heart Failure with Preserved Ejection Fraction: Post-Hoc Analysis of the Randomized, Placebo-Controlled TOPCAT Trial

Mechanisms and Drug Development in Atrial Fibrillation

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