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

Abstract

Background: Spironolactone is currently used in a large proportion of patients with heart failure and preserved ejection fraction (HFpEF), yet its effects on cardiac structure and function in a large population has not been well established. Aims: To study the impact of spironolactone on key echocardiographic parameters in HFpEF. Methods: Individual-patient-data meta-analysis of three randomized trials (HOMAGE, ALDO-DHF, and TOPCAT) comparing spironolactone (9-12 months exposure) to placebo (or control) on the changes of left atrial volume indexed (LAVi), left ventricular mass indexed (LVMi), inter-ventricular 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 were used to test the effect of spironolactone on echocardiographic changes. Results: A total of 984 patients were included in this analysis: HOMAGE=452 (45. 9%), ALDO-DHF=398 (40. 4%), and TOPCAT=134 (13. 6%). 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 VSports app下载. 8 to 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 (interactionP<0. 01). Conclusions: Spironolactone improved cardiac structure and function of patients with HFpEF.