Mineralocorticoid receptor antagonists and atrial fibrillation: a meta-analysis

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

Aldosterone has been implicated in atrial remodelling representing a potential target for upstream therapies. Accumulating evidence suggests that mineralocorticoid receptor blockade may have favourable effects on atrial fibrillation (AF) development, although some controversial results have been published. We, therefore, conducted a meta-analysis of randomized clinical trials (RCTs) and observational studies in order to examine the protective role of mineralocorticoid receptor antagonists (MRAs) on AF.

Related collections

Most cited references 14

Record: found
Abstract: found
Article: not found

Aldosterone mediates angiotensin II-induced interstitial cardiac fibrosis via a Nox2-containing NADPH oxidase.

Ajay Shah, David J. Grieve, Angad Johar … (2006)

Angiotensin (ANG) II (AngII) and aldosterone contribute to the development of interstitial cardiac fibrosis. We investigated the potential role of a Nox2-containing NADPH oxidase in aldosterone-induced fibrosis and the involvement of this mechanism in AngII-induced effects. Nox2-/- mice were compared with matched wild-type controls (WT). In WT mice, subcutaneous (s.c.) AngII (1.1 mg/kg/day for 2 wk) significantly increased NADPH oxidase activity, interstitial fibrosis (11.5+/-1.0% vs. 7.2+/-0.7%; P<0.05), expression of fibronectin, procollagen I, and connective tissue growth factor mRNA, MMP-2 activity, and NF-kB activation. These effects were all inhibited in Nox2-/- hearts. The mineralocorticoid receptor antagonist spironolactone inhibited AngII-induced increases in NADPH oxidase activity and the increase in interstitial fibrosis. In a model of mineralocorticoid-dependent hypertension involving chronic aldosterone infusion (0.2 mg/kg/day) and a 1% Na Cl diet ("ALDO"), WT animals exhibited increased NADPH oxidase activity, pro-fibrotic gene expression, MMP-2 activity, NF-kB activation, and significant interstitial cardiac fibrosis (12.0+/-1.7% with ALDO vs. 6.3+/-0.3% without; P<0.05). These effects were inhibited in Nox2-/- ALDO mice (e.g., fibrosis 6.8+/-0.8% with ALDO vs. 5.8+/-1.0% without ALDO; P=NS). These results suggest that aldosterone-dependent activation of a Nox2-containing NADPH oxidase contributes to the profibrotic effect of AngII in the heart as well as the fibrosis seen in mineralocorticoid-dependent hypertension.

0 comments Cited 70 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

A comparison of the aldosterone-blocking agents eplerenone and spironolactone.

Allan A. Struthers, Henry Krum, Gordon Williams (2008)

Improved understanding of the adverse pharmacological properties of aldosterone has prompted investigation of the clinical benefits of blocking aldosterone at the receptor level. This article reviews the pharmacology, clinical efficacy, and tolerability of the two available blocking agents, spironolactone and eplerenone. A Medline search identified clinical studies assessing spironolactone and eplerenone. Priority was given to large, well-controlled, clinical trials and comparative studies. Pharmacological differences between spironolactone and eplerenone include lower affinity of eplerenone for progesterone, androgen, and glucocorticoid receptors; more consistently demonstrated nongenomic properties for eplerenone; and the presence of long-acting metabolites for spironolactone. Both agents effectively treat hypertension and heart failure but comparisons are complicated by the deficiency of head-to-head trials and differences between patient populations. There are differences in the tolerability profiles; spironolactone is associated with dose-dependent sexual side effects. Both agents produce dose-dependent increases in potassium concentrations, although the effect with spironolactone appears to be greater when both agents are administered at recommended doses. Choice of a specific agent should be based on individual patient issues, such as the nature of heart failure and patient concerns about adverse events. Copyright (c) 2008 Wiley Periodicals, Inc.

0 comments Cited 51 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Upstream therapies for management of atrial fibrillation: review of clinical evidence and implications for European Society of Cardiology guidelines. Part II: secondary prevention.

Irene Savelieva, Nicholaos Kakouros, Antonios Kourliouros … (2011)

Fundamental research into molecular mechanisms of atrial fibrillation (AF) and improved understanding of processes involved in the initiation and maintenance of AF have transformed the traditional approach to its management by targeting only the electrical aspects, usually with antiarrhythmic drugs and, recently, by ablation. The antiarrhythmic potential of upstream therapies, such as angiotensin-converting enzyme inhibitors, angiotensin receptor blockers (ARBs), statins, and n-3 (ω-3) polyunsaturated fatty acids, extends beyond the benefit of treating underlying heart disease to modifying the atrial substrate and intervening in specific mechanisms of AF. The key target is structural remodelling of the atria, particularly inflammation and fibrosis, although there is evidence to suggest the direct involvement at the ion channel level. Positive clinical reports supported by robust experimental data have suggested that upstream therapies can be valuable strategies for primary prevention of AF in selected patients and have resulted in several class IIA recommendations in the new European guidelines on AF. However, these results have not been consistently replicated in the secondary prevention setting, and several recent randomized controlled studies failed to demonstrate any effect of upstream therapies on AF burden or on major cardiovascular outcomes. Part II of the review summarizes the evidence base for the use of upstream therapies for secondary prevention of AF.

0 comments Cited 43 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Journal

Title: Europace

Abbreviated Title: Europace

Publisher: Oxford University Press (OUP)

ISSN (Print): 1099-5129

ISSN (Electronic): 1532-2092

Publication date Created: May 25 2016

Publication date Created: May 2016

Publication date (Print): May 2016

Publication date (Electronic): December 23 2015

Volume: 18

Issue: 5

Pages: 672-678

Article

DOI: 10.1093/europace/euv366

PubMed ID: 26705563

SO-VID: 3c03e0fd-4b8d-4cdf-8369-5a575aaf44a3

History

Data availability:

Comments

Comment on this article

scite_

Cited by 14

See all cited by

Most referenced authors 335

See all reference authors

- Version 1
- Version 1

Mineralocorticoid receptor antagonists and atrial fibrillation: a meta-analysis

Read this article at

Abstract

Related collections

Road 2 Open Meta

Most cited references 14

Aldosterone mediates angiotensin II-induced interstitial cardiac fibrosis via a Nox2-containing NADPH oxidase.

A comparison of the aldosterone-blocking agents eplerenone and spironolactone.

Upstream therapies for management of atrial fibrillation: review of clinical evidence and implications for European Society of Cardiology guidelines. Part II: secondary prevention.

Author and article information

Journal

Article

History

Comments

Comment on this article

Similar content 4,116

Cited by 14

Most referenced authors 335