Effects of mineralocorticoid receptor antagonists in patients with preserved ejection fraction: a meta-analysis of randomized clinical trials

Abstract

Background: Mineralocorticoid receptor antagonists (MRAs) have been shown to be effective in patients with heart failure or myocardial infarction complicated by a reduced ejection fraction. However, the role of MRAs in patients with preserved ejection fraction (PEF) remains to be clarified. We aimed to summarize the evidence for the efficacy of MRAs in patients with either heart failure with PEF (HF-PEF) or myocardial infarction with PEF (MI-PEF).

Methods: We searched PubMed, EMBASE, Cochrane Library, and clinical trials databases for randomized controlled trials, through June 2014, assessing MRA treatment in HF-PEF or MI-PEF patients. Fourteen randomized controlled trials (MI-PEF, 5; HF-PEF, 9; n = 6,428 patients) were included.

Results: MRA treatment reduced the risk of hospitalization for heart failure (relative risk, 0.83; 95% confidence interval [CI], 0.70 to 0.98), improved quality of life (weighted mean difference [WMD], -5.16; 95% CI, -8.03 to -2.30), left ventricular end-diastolic diameter (standardized mean difference, -0.21; 95% CI, 0.32 to -0.11), and serum amino-terminal peptide of procollagen type-III level (WMD, -1.50, 95% CI, -1.72 to -1.29) in patients with PEF. In addition, MRAs reduced E/e'(an echocardiographic estimate of filling pressure for assessment of diastolic function; WMD, -1.82; 95% CI, -2.23 to -1.42) in HF-PEF patients and E/A ratio (the ratio of early to late diastolic transmitral flow; WMD, 0.12; 95% CI, 0.10 to 0.14) in MI-PEF patients. However, all-cause mortality was not improved by MRAs in either HF-PEF (P = 0.90) or MI-PEF (P = 0.27) patients.

Conclusions: MRA treatment in PEF patients led to reduced hospitalization for heart failure, quantifiable improvements in quality of life and diastolic function, and reversal of cardiac remodeling, but did not provide any all-cause mortality benefit.

Figure 1

Flowchart of study search and selection in this meta-analysis. MI, Myocardial infarction; MRAs, Mineralocorticoid receptor antagonists; RCTs, Randomized controlled trials.

Figure 2

Pooled analyses of all-cause mortality and hospitalization for heart failure in the mineralocorticoid receptor antagonist group versus controls. (A) All-cause hospitalization; (B) Hospitalization due to heart failure. CI, Confidence interval; MRA, Mineralocorticoid receptor antagonist; RD, Absolute risk reduction; RR, Relative risk.

Figure 3

Forest plots for effect of MRAs on echo indexes of diastolic function. (A) Changes in E/e'; (B) E/A ratio changes; (C) DT changes; (D) IVRT changes. CI, Confidence interval; DT, E-wave deceleration time; E/A ratio, the ratio of early to late diastolic transmitral flow; E/e', an echocardiographic estimate of filling pressure for assessment of diastolic function; IVRT, Isovolumic relaxation time; MRA, Mineralocorticoid receptor antagonist; WMD, Weighted mean difference.

Figure 4

Forest plots for effect of MRAs on indexes of cardiac structure and function. (A) LVEF changes; (B) LVEDD changes; (C) LAVI changes; (D) LVMI changes. CI, Confidence interval; LAVI, Left atrial volume index; LVEDD, Left ventricular end-diastolic diameter; LVEF, Left ventricular ejection fraction; LVMI, Left ventricular mass index; SMD, Standardized mean difference; MRA, Mineralocorticoid receptor antagonist; WMD, Weighted mean difference.

Figure 5

Forest plots for effect of mineralocorticoid receptor antagonists on serum indicators and functional capacity. (A) Quality of life changes; (B) 6-MWD changes; (C) PIIINP changes; (D) BNP changes. 6-MWD, 6-minute walk distance; BNP, B-type natriuretic peptide; CI, Confidence interval; KCCQ CSS, Kansas City Cardiomyopathy Questionnaire clinical summary score; PIIINP, Serum amino-terminal peptide of procollagen type-III; MLWHF, Minnesota Living with Heart Failure questionnaire; MRA, Mineralocorticoid receptor antagonist; WMD, Weighted mean difference.