# Use of Spironolactone for the Treatment of Heart Failure With Preserved Ejection Fraction: Efficacy and Clinical Implications in Light of Recent Evidence

## TL;DR

This paper reviews spironolactone's potential in treating heart failure with preserved ejection fraction, highlighting its benefits and limitations based on recent studies.

## Contribution

The paper provides a systematic review of spironolactone's efficacy in HFpEF, emphasizing the need for personalized treatment strategies.

## Key findings

- Spironolactone reduces cardiovascular events and improves diastolic function in HFpEF patients.
- Treatment response varies by region, with prior hospitalization affecting outcomes differently in America versus Russia and Georgia.
- Adverse effects like hyperkalemia and gynecomastia limit spironolactone's use despite its benefits.

## Abstract

Heart failure with preserved ejection fraction (HFpEF) is a common condition that affects around half of individuals with heart failure (HF), which is associated with significant morbidity, mortality, and reduced quality of life. Even though there is a high prevalence, no pharmacological treatments have been proven to reduce mortality in HFpEF. Spironolactone has shown promise in improving diastolic function and decreasing ventricular stiffness in HFpEF patients. The drug’s mechanism of action, involving aldosterone blockade, may help reduce fibrosis and inflammation, which play a role in the development of HFpEF. We analyzed articles published over the last 18 years using PubMed and the Medical Subject Headings (MeSH) strategy for this review. Using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and other inclusion and exclusion criteria, eighteen review articles were selected to assess the efficacy of spironolactone for HFpEF, focusing on randomized controlled trials, meta-analyses, and observational studies. These 18 selected review articles consist of a review of the effects of spironolactone on HF. One of the clinical trials, the treatment of Preserved Cardiac Function Heart Failure (TOPCAT), showed that spironolactone can reduce the incidence of major clinical events, which include cardiovascular death and rehospitalizations. Due to the variability in treatment responses among different treatment groups, personalized treatment may provide optimal results. Such as in America, patients enrolled based on a prior HF hospitalization had significantly higher rates of cardiovascular mortality, HF hospitalizations, and all-cause mortality compared to those enrolled based on B-type natriuretic peptide (BNP) levels. However, in Russia and Georgia, prior hospitalization was not linked to increased risk of death or the primary outcome, though it was associated with more HF hospitalizations, likely because no adjudicated HF events occurred in the BNP group in that region. Even though spironolactone reduces cardiovascular events and improves specific events, its effectiveness is unclear due to the variability in the treatment response and the absence of long-term data. Adverse effects of spironolactone include hyperkalemia, worsening renal function, gynecomastia, and hypotension. This review underscores the need for personalized treatment strategies due to heterogeneity in trial outcomes and further well-designed studies to establish its definitive role in HFpEF management and address critical knowledge gaps in this challenging condition.