Effects of spironolactone in heart failure with preserved ejection fraction: A meta-analysis of randomized controlled trials

Abstract

Background: Heart failure with preserved ejection fraction (HFpEF) is a common syndrome, accounting for more than one half of all heart failure patients, which is associated with high morbidity and mortality. But there is little evidence-based therapeutic strategies for the management of HFpEF. Previous studies reported the effects of spironolactone on HFpEF; however, the results were inconsistent. In this meta-analysis, we evaluated the effects of spironolactone on HFpEF.

Methods: Articles were searched on PubMed, EMBASE, and COCHRANE databases before May, 2017, and were supplemented by hand searches of reference lists of included studies and review articles. Eligible articles were restricted to randomized controlled trials (RCTs). The odds ratios (ORs) of the dichotomous data, mean difference (MD) of continuous data, and 95% confidence intervals (CIs) were calculated to assess the effects of spironolactone in patients with HFpEF.

Results: A total of 7 studies including 4147 participants were analyzed. There were significant improvements on the E/e' index (MD -1.38; 95% CI, -2.03 to -0.73; P < .0001) and E/A velocity ratio (MD -0.05; 95% CI, -0.10 to -0.00; P = .03) under spironolactone treatment compared with placebo, while there was no effect on the deceleration time (MD 1.04; 95% CI, -8.27 to 10.35; P = .83). Subgroup analyses on the E/A velocity ratio showed that there was obvious benefit from spironolactone therapy in patients with follow-up periods >6 months but not in those with follow-up periods ≤6 months. There was no reduction in all-cause mortality and hospitalization compared with placebo. And no improvement in 6-minute walk distance was seen compared with placebo.

Conclusion: This meta-analysis demonstrates that the use of spironolactone improves left ventricular diastolic function in patients with HFpEF, whereas it has no effect on all-cause mortality and hospitalization, and the 6-minute walk distance. Further larger size, multicenter, RCTs are required to confirm the effects of spironolactone on patients with HFpEF.

Figure 1

Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flow diagram of study selection.

Figure 2

Forest plots of the E/A velocity ratio and DT between spironolactone group (experimental group) and control group. DT = deceleration time, E/A velocity ratio = ratio of early to late mitral flow.

Figure 3

Forest plots of subgroup analyses on the ratio of early to late mitral flow (E/A velocity ratio). (A) The effect of age on the E/A velocity ratio, (B) the effect of follow-up period on the E/A velocity ratio, and (C) the effect of dosage of spironolactone on the E/A velocity ratio.