The Evolving Role of Steroidal and Nonsteroidal MRAs in HFmrEF and HFpEF
The Evolving Role of Steroidal and Nonsteroidal MRAs in HFmrEF and HFpEF
Source: Highlighted in PACE-CME, June 2025 Update, based on RALES, TOPCAT, FIDELIO-DKD, FIGARO-DKD, and FINEARTS-HF trials.
Journal: JACC: Heart Failure
Introduction:
Heart failure with mildly reduced (HFmrEF) and preserved ejection fraction (HFpEF) continues to present clinical challenges. For years, treatment was limited and mostly supportive. However, the evolving use of mineralocorticoid receptor antagonists (MRAs)—both steroidal and nonsteroidal—has reshaped therapeutic strategies in these patient populations.
1. Historical Context: Steroidal MRAs
• RALES (1999): Demonstrated a significant mortality benefit from spironolactone in HFrEF. Spironolactone remains widely used in clinical practice, especially for HFrEF, due to its proven efficacy and low cost.
• TOPCAT (2014): Studied spironolactone in HFpEF. While overall results were neutral, a subgroup analysis (Americas cohort) showed reduced heart failure hospitalizations, suggesting a role for MRAs in select HFpEF patients.
2. The Emergence of Nonsteroidal MRAs
• Finerenone, a nonsteroidal MRA, has high receptor specificity and a reduced risk of anti-androgenic side effects or hyperkalemia. It represents a safer and more targeted approach, especially in patients with chronic kidney disease (CKD) or diabetes.
3. The Turning Point: FINEARTS-HF Trial (2023–2024)
• Study Design: Multinational, randomized controlled trial assessing finerenone in HFmrEF and HFpEF (LVEF >40%).
• Key Outcomes:
• Significant reduction in the composite of CV death and HF hospitalization.
• Benefits observed across all subgroups, including women and patients with CKD.
• Lower risk of hyperkalemia compared to traditional MRAs.
4. Clinical Implications
• Practice Shift: Finerenone may become a preferred MRA in HFmrEF/HFpEF, particularly for high-risk populations.
Note (outside the article):
Guidelines from AHA/ACC/HFSA 2022 and ESC 2021 give MRAs a Class IIb recommendation for HFmrEF and HFpEF. This may change as new data from trials like FINEARTS-HF emerge.
JACC Article: https://www.jacc.org/doi/abs/10.1016/j.jchf.2025.03.041