Spironolactone effect on cardiac structure and function of patients with heart failure and preserved ejection fraction: a pooled analysis of three randomized trials

Eur J Heart Fail. 2023 Jan;25(1):108-113. doi: 10.1002/ejhf.2726. Epub 2022 Nov 9.

Abstract

Aims: Spironolactone is currently used in a large proportion of patients with heart failure and preserved ejection fraction (HFpEF), yet its effect on cardiac structure and function in a large population has not been well established. The aim of this study was to evaluate the impact of spironolactone on key echocardiographic parameters in HFpEF.

Methods and results: An individual-patient-data meta-analysis of three randomized trials (HOMAGE, Aldo-DHF, and TOPCAT) was performed comparing spironolactone (9-12 month exposure) to placebo (or control) for the changes in left atrial volume index (LAVi), left ventricular mass index (LVMi), interventricular septum (IVS) thickness, E/e' ratio, and left ventricular ejection fraction (LVEF) among patients with stage B (HOMAGE) or C (Aldo-DHF and TOPCAT) HFpEF. Analysis of covariance was used to test the effect of spironolactone on echocardiographic changes. A total of 984 patients were included in this analysis: 452 (45.9%) from HOMAGE, 398 (40.4%) from Aldo-DHF, and 134 (13.6%) from TOPCAT. The pooled-cohort patient's median age was 71 (66-77) years and 39% were women. Median LAVi was 29 (24-35) ml/m2 , LVMi 100 (84-118) g/m2 , IVS thickness 12 (10-13) mm, E/e' ratio 11 (9-13), and LVEF 64 (59-69)%. Spironolactone reduced LAVi by -1.1 (-2.0 to -0.1) ml/m2 (p = 0.03); LVMi by -3.6 (-6.4 to -0.8) g/m2 (p = 0.01); IVS thickness by -0.2 (-0.3 to -0.1) mm (p = 0.01); E/e' ratio by -1.3 (-2.4 to -0.2) (p = 0.02); and increased LVEF by 1.7 (0.8-2.6)% (p < 0.01). No treatment-by-study heterogeneity was found except for E/e' ratio with a larger effect in Aldo-DHF and TOPCAT (interaction p < 0.01).

Conclusions: Spironolactone improved cardiac structure and function of patients with HFpEF.

Keywords: Cardiac structure and function; Echocardiography; HFpEF; Spironolactone; Treatment effect.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Female
  • Heart Failure* / diagnostic imaging
  • Heart Failure* / drug therapy
  • Heart Failure* / epidemiology
  • Humans
  • Male
  • Mineralocorticoid Receptor Antagonists
  • Randomized Controlled Trials as Topic
  • Spironolactone* / therapeutic use
  • Stroke Volume
  • Ventricular Function, Left

Substances

  • Spironolactone
  • Mineralocorticoid Receptor Antagonists