Mineralocorticoid Receptor Antagonists in Heart Failure with Preserved Ejection Fraction: A Systematic Review and Meta-Analysis

Background/Objectives: Heart failure with preserved ejection fraction (HFpEF) is a complex clinical syndrome with limited therapeutic options. Mineralocorticoid receptor antagonists (MRAs) have been shown to improve clinical outcomes in patients with heart failure with reduced ejection fraction (HFrEF), but their use in patients with HFpEF remains controversial. The aim of this review is to evaluate whether the use of MRAs improves diastolic function, functional capacity, and quality of life in patients with HFpEF. Methods: A systematic literature search of scientific databases was performed to identify studies comparing the use of MRAs to placebo or no treatment in adult patients with HFpEF (2000-2024; English; PROSPERO registration CRD42022300783). Data were meta-analysed using a random-effects model for overall effect size measured as the standardised mean difference. Results: Pooled data revealed a significant benefit of MRA use compared to the control in decreasing E/e' (SMD -0.21; 95% CI: -0.33 to -0.10, p = 0.00), with greater improvement seen with longer duration of treatment. A substantial reduction in systolic blood pressure (SMD -0.27; 95% CI: -0.53 to -0.02, p = 0.03) and diastolic blood pressure (SMD -0.18; 95% CI: -0.32 to -0.04, p = 0.01) was also noted. There was no significant difference in the 6 min walk distance, peak exercise capacity, or quality-of-life measures. Adverse events such as hyperkalaemia and worsening renal function were frequently reported in the MRA group. Conclusions: MRAs improve echocardiographic parameters of diastolic function and BP control; however, this did not translate into clinical outcomes of improved functional capacity or quality of life.