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Role of MRAs in Heart Failure Treatment
Panelists discuss how mineralocorticoid receptor antagonists (MRAs) remain underutilized despite being foundational therapy for heart failure with reduced ejection fraction due to clinician fears of hyperkalemia and renal dysfunction, while new nonsteroidal MRAs like finerenone show promise across the ejection fraction spectrum with potentially improved adverse effect profiles, though questions remain about their incremental benefit over traditional steroidal MRAs given their substantially higher cost.
EP: 1.Economic Burden of Heart Failure Care
EP: 2.Heart Failure Prevalence and Screening
EP: 3.Quality Metrics in Heart Failure
EP: 4.Heart Failure Stages and Impact of Delayed Diagnosis
EP: 5.Collaboration in Heart Failure Treatment
EP: 6.Guideline-Directed Medical Therapies in Heart Failure
EP: 7.β-Blockers for Treatment of Heart Failure
EP: 8.Role of Diuretics in Heart Failure Management
EP: 9.Treatment of Heart Failure With ARNI Therapy
EP: 10.SGLT2 Inhibitors for Treatment of Heart Failure
EP: 11.GLP-1 for Treatment of Heart Failure
EP: 12.Role of MRAs in Heart Failure Treatment
Steroidal vs Nonsteroidal MRAs in Heart Failure
Nonsteroidal mineralocorticoid receptor antagonists (MRAs) differ fundamentally from steroidal agents through their molecular structure, lacking the 4 interlocking steroid rings that characterize spironolactone and eplerenone. This structural difference eliminates binding to steroid hormone receptors, potentially reducing steroid-related adverse effects like gynecomastia while maintaining selective mineralocorticoid receptor antagonism. Additionally, nonsteroidal agents demonstrate different tissue distribution patterns and shorter half-lives, which may contribute to improved tolerability profiles.
The clinical evidence supporting nonsteroidal MRAs spans both heart failure and chronic kidney disease populations. FINEARTS-HF demonstrated cardiovascular death and heart failure hospitalization benefits in patients with symptomatic heart failure with ejection fraction above 40%, while FIDELITY and FIGARO trials established kidney outcome benefits in patients with diabetic kidney disease. Phase 2 data suggest potentially lower hyperkalemia risks, though phase 3 evidence requires careful interpretation to confirm these safety advantages.
The combination of nonsteroidal MRAs with SGLT2 inhibitors appears particularly promising, with evidence from trials like CONFIDENCE demonstrating additive benefits when combining finerenone with SGLT2 inhibition compared to either agent alone. SGLT2 inhibitors may actually potentiate MRA effects while reducing hyperkalemia risk, supporting concurrent initiation rather than sequential therapy. However, the substantial cost differential between generic steroidal and branded nonsteroidal agents raises important questions about incremental value, requiring comparative effectiveness research to guide optimal implementation strategies in clinical practice.
