Effects of Mineralocorticoid Receptor Antagonists on Atrial Fibrillation Occurrence: A Systematic Review, Meta‐Analysis, and Meta‐Regression to Identify Modifying Factors

Figures

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  Figure 1. Flow diagram of study selection. Clinical trials (randomized, nonrandomized, parallel arm, and cluster designs) and clinical observational comparative studies (including retrospective or prospective cohorts, case‐control, or nested case‐control designs) were included. *Trials registry portals include clinicaltrials.gov (https://clinicaltrials.gov/), the World Health Organization international clinical trials registry platform (http://apps.who.int/trialsearch/), the UK clinical trials gateway (https://www.ukctg.nihr.ac.uk/), EudraCT (https://eudract.ema.europa.eu/).

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  Figure 2. Atrial fibrillation occurrence comparing mineralocorticoid receptor antagonist (MRAs) therapy vs controls.

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  Figure 3. Mineralocorticoid receptor antagonist (MRA) benefit in reducing the risk for atrial fibrillation (AF) occurrence in subgroups analyses regarding the type of AF (A) (new‐onset AF vs AF recurrence), the presence or not of heart failure with reduced ejection fraction (HFrEF) (B) (HFrEF, defined as patients with left ventricular ejection fraction [LVEF] ≤40% and New York Heart Association [NYHA] class ≥II), the study status (C) (full‐text and published studies vs meetings abstracts or unpublished studies), and individual MRA used (D). Circle sizes are proportional to trial sample sizes. CR indicates canrenone; EP, eplerenone; NS, nonspecified MRA; OR, odds ratio; SP, spironolactone.

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  Figure 4. Treatment effects (both mineralocorticoid receptor antagonists [MRAs] and controls) on atrial fibrillation (AF) occurrence were associated with a high AF occurrence rate in the control group (A) but not with the AF occurrence rate in the MRA group (B). Treatment effects (both in the MRA group and controls) on AF occurrence were associated with the year of publication of the study (C). Circle sizes are log‐proportional to trial sample sizes. Blue (AF occurrence panels) and red (year of publication panel) circles indicate trials with a positive primary outcome effect (AF occurrence, as defined by the trial authors).