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Expanding Role of MRAs in Heart Failure
Expanding Role of MRAs in Heart Failure: Bridging the Gap Between Evidence and Clinical Practice

Released: April 22, 2025

Expiration: April 21, 2026

Scott D. Solomon
Scott D. Solomon, MD
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Key Takeaways
  • There remains a significant gap between clinical evidence and practice, especially concerning the use of mineralocorticoid receptor antagonists.
  • Hesitancy among healthcare professionals may be driven by inconsistent trial results, concerns about hyperkalemia and renal dysfunction, and a lack of definitive guideline-defining data.
  • The FINEARTS-HF trial demonstrated a statistically significant reduction in cardiovascular death or heart failure events with finerenone in patients with HFmrEF or HFpEF.

Recognizing the unmet therapeutic need for patients with heart failure (HF) with mildly reduced ejection fraction (HFmrEF) or preserved ejection fraction (HFpEF) requires a nuanced understanding of the evolving treatment landscape. Despite growing evidence and updated guideline recommendations, there remains a significant gap between clinical evidence and practice, especially concerning the use of mineralocorticoid receptor antagonists (MRAs). MRAs, such as spironolactone and eplerenone, historically have demonstrated compelling benefits in patients with HF with reduced ejection fraction (HFrEF), including reduced risk of mortality and hospitalization. However, their adoption in treating HFmrEF and HFpEF has been far more limited in clinical trials and real-world practice.

The phase III TOPCAT trial—evaluating spironolactone vs placebo—is pivotal in this discussion. Although it did not meet its composite primary endpoint across the entire HFpEF population, a regional subgroup analysis showed a significant reduction in HF-related hospitalizations among those enrolled in the Americas (Canada, US, Brazil, and Argentina) vs Russia- and Georgia-based participants. This suggests a possible treatment effect in a more rigorously diagnosed cohort. In addition, a post hoc analysis indicated that spironolactone may improve outcomes in patients with HFpEF and resistant hypertension, highlighting a potential benefit in targeted subgroups. These findings, while exploratory and not definitive, signal that MRAs could offer therapeutic value beyond HFrEF, in particular, among heterogeneous HFpEF and HFmrEF populations.

Barriers to MRA Use in Practice
Despite these insights, MRAs are underprescribed in HF, especially among patients with HFrEF where they have received class I indications. CHAMP-HF registry data indicate that only one third of eligible patients with HFrEF are not prescribed an MRA. Although comparable real-world data are limited in HFmrEF and HFpEF, available evidence and clinical experience suggest that MRA use is even lower among these populations. Hesitancy among healthcare professionals (HCPs) may be driven by several factors, including inconsistent trial results, concerns about hyperkalemia and renal dysfunction, as well as a lack of definitive, guideline-defining data. These concerns are not without merit. Steroidal MRAs do carry risks of hyperkalemia and worsening renal function that are especially concerning for patients with chronic kidney disease or diabetes mellitus, which are highly prevalent comorbidities with HFpEF. While these risks are not unique to steroidal agents, their frequency and severity may vary depending on patient characteristics and the specific MRA used.

Emerging Nonsteroidal MRAs for HF
The therapeutic landscape is beginning to shift with the emergence of nonsteroidal MRAs like finerenone. The FINEARTS-HF trial represents a significant step forward, as finerenone demonstrated a statistically significant reduction in the composite outcome of cardiovascular death or HR events vs placebo in patients with HFmrEF or HFpEF. These early findings suggest the potential for MRAs to benefit a broader patient population with HF and need for further evaluation of finerenone as a safer and more targeted option. In particular, finerenone might be efficacious and safe in patients with type 2 diabetes and chronic kidney disease, as demonstrated in the FIDELIO-DKD and FIGARO-DKD trials, which include populations that often overlap with the HFpEF patient population.

Despite these advances, clinical inertia remains a formidable barrier. Implementation science has long documented the delay in translating high-quality evidence into clinical practice. Contributing factors include limited access to new research, time constraints, lack of clarity in interpreting data, and resistance to change. These barriers are particularly relevant in the context of HF, where disease phenotyping is diverse, the evidence base is evolving, and therapeutic decisions often rely on clinical judgment vs standardized pathways.

Guideline Recommendations and Future Directions
The 2022 HF guidelines cautiously recommend MRA as an add-on therapy in HFpEF and HFmrEF (class IIb) to reduce HF hospitalizations. This reflects a measured but progressive stance on the issue. As such, HCPs are faced with both an opportunity and responsibility to recognize the unmet needs of patients with HFmrEF or HFpEF, as well as to bridge the evidence-practice gap by integrating new, validated therapies into routine care. The take-home message: HCPs must continue to monitor developments in this space to ensure that we provide optimal and evidence-informed care for patients across the HF spectrum.

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