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Expanding Role of Finerenone in Heart Failure
Expanding Role of MRAs in Heart Failure: Nonsteroidal Finerenone Improves Patient Outcomes and Quality of Life

Released: July 09, 2025

Expiration: July 08, 2026

Ty J. Gluckman
Ty J. Gluckman, MD, MHA
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Key Takeaways
  • SGLT2 inhibitors and mineralocorticoid receptor antagonists (MRAs) are transforming the treatment landscape for patients with HFmrEF and HFpEF.
  • Finerenone is a nonsteroidal MRA that has enhanced selectivity and a favorable safety profile compared with steroidal MRAs like spironolactone and eplerenone.
  • The FINEARTS-HF trial established finerenone as a critical therapy for patients with HFmrEF and HFpEF by significantly reducing the risk of composite cardiovascular-related death and hospitalization for a heart failure event.

Heart failure with mildly reduced ejection fraction (HFmrEF) and heart failure with preserved ejection fraction (HFpEF) together account for over half of all cases of heart failure. Patients with these conditions tend to be older, more often female, and frequently have other comorbidities, such as obesity, hypertension, type 2 diabetes (T2D), and chronic kidney disease (CKD). Despite having a similar prognosis as patients with heart failure with reduced ejection fraction (HFrEF), therapeutic options for HFmrEF and HFpEF have traditionally been more limited. However, the treatment landscape has shifted in recent years, with sodium-glucose cotransporter 2 (SGLT2) inhibitors and mineralocorticoid receptor antagonists (MRAs) leading the change in HFmrEF and HFpEF treatment for the better.

Patients with HFmrEF and HFpEF face an increased risk of death and hospitalization, limited quality of life, and reduced functional capacity. In fact, patients with HFpEF face a 1.4-fold higher rate of hospitalization compared with other heart failure phenotypes. Part of this may be due to comorbidity burden and varying pathophysiologic contributors to HFpEF, including inflammation, myocardial fibrosis, endothelial dysfunction, and neurohormonal activation. HFpEF may result from abnormal metabolic risk factors and CKD—collectively known as cardiovascular-renal-metabolic syndrome—which can further complicate treatment. In this context, MRAs have the potential to favorably impact many of these conditions.

Revisiting MRAs: Mechanistic Rationale and Clinical Evidence
MRAs antagonize the effects of aldosterone at the mineralocorticoid receptor and mitigate sodium retention, potassium loss, inflammation, and fibrosis. Steroidal MRAs like spironolactone and eplerenone have long been shown to produce significant benefits in HFrEF, including reduction in the risk of death and hospitalization for worsening heart failure. Previous investigations of their use in HFmrEF and HFpEF have been limited by mixed results and safety concerns.

In the TOPCAT trial, which evaluated spironolactone vs placebo in patients with symptomatic HFmrEF and HFpEF, no significant benefit was demonstrated for the primary composite endpoint of cardiovascular (CV)-related death, aborted cardiac arrest, or hospitalization for heart failure. Although marked regional differences in some benefit was demonstrated in a post-hoc analysis, the potential for hyperkalemia and undesirable hormonal effects likely contribute to its underutilization.

Enter Finerenone: A Targeted Approach
Finerenone is a nonsteroidal MRA that offers enhanced receptor selectivity and a more favorable safety profile. Unlike spironolactone, finerenone has minimal interaction with androgen or progesterone receptors, reducing the risk of undesirable hormonal effects like gynecomastia or menstrual irregularities. It also appears to carry a more manageable hyperkalemia risk when used with appropriate monitoring.

Previous trials in patients with T2D and CKD demonstrated that finerenone can reduce the risk of adverse kidney and CV events. Building on this foundation, the FINEARTS-HF trial sought to evaluate the effects of finerenone in patients with HFmrEF and HFpEF (ie, left ventricular ejection fraction [LVEF] of 40% or more). This international trial randomized approximately 6000 patients to receive either finerenone 20-40 mg daily or placebo on top of their usual care for a median follow-up of 32 months. The primary composite endpoint included CV-related death and total worsening heart failure events.

Finerenone treatment led to a significant reduction in the primary composite endpoint (rate ratio: 0.84; P =.007) as well as in worsening heart failure events alone (rate ratio: 0.82; P =.006) vs placebo. Patients treated with finerenone also experienced a modest yet statistically significant improvement in quality of life. These benefits were consistent across multiple subgroups, including those with or without SGLT2 inhibitor treatment at baseline and those with varying degrees of renal dysfunction. Of note, hyperkalemia continues to be the primary safety concern with MRAs. It was more commonly reported in the finerenone arm vs the placebo arm in FINEARTS-HF, but the incidence of serious adverse events was low. In addition, treatment discontinuation and hospitalization due to hyperkalemia were uncommon. Routine monitoring of serum potassium and renal function is essential, especially in patients with CKD and/or who are receiving treatment with an ACE inhibitor, ARB, or ARNI.

Applying the Evidence in Practice
The implications of FINEARTS-HF are significant. Consider a 68-year-old man with HFmrEF (LVEF: 43%), T2D, stage IIIa CKD (eGFR: 52 mL/min/1.73m²), and New York Heart Association (NYHA) class II functional status. His current treatment comprises an ARNI, beta blocker, SGLT2 inhibitor, and loop diuretic. The findings from FINEARTS-HF support the addition of finerenone to this patient’s treatment regimen to reduce the risk of adverse CV events accompanied by an acceptable safety profile. The same can be said about a 74-year-old woman with HFpEF (LVEF: 55%), obesity, hypertension, NYHA class III functional status, and recurrent hospitalizations despite treatment with an ARB, SGLT2 inhibitor, and loop diuretic. In both cases, the approach is the same: proactively assess treatment eligibility, initiate therapy judiciously, and monitor patients appropriately. As with all heart failure therapies, a multidisciplinary approach that engages primary care, cardiology, and nephrology may be needed to optimize patient outcomes.

Although the management of HFmrEF and HFpEF has long been constrained by therapeutic uncertainty and limited options, finerenone has emerged as an effective and well-tolerated treatment option that offers new possibilities for improving outcomes. By reducing hospitalizations and enhancing symptom control, finerenone fills a critical gap in the treatment landscape for these patients. As healthcare professionals, the imperative is clear: recognize appropriate candidates, overcome therapeutic inertia, and implement evidence-based strategies that reflect the data. With the addition of nonsteroidal MRAs to our therapeutic toolkit, we are better equipped to address the complex needs of patients with HFmrEF and HFpEF.

Your Thoughts
How often do you prescribe finerenone for your patients with HFmrEF or HFpEF? You can get involved in the discussion by answering the poll question and posting a comment below.

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