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Steroidal vs Nonsteroidal MRAs in Heart Failure
Panelists discuss how nonsteroidal MRAs like finerenone differ mechanistically from steroidal MRAs by lacking steroid rings (reducing steroid-related adverse effects like gynecomastia), having different mineralocorticoid receptor binding patterns, shorter half-lives, and potentially lower hyperkalemia risk, with strong evidence supporting their use in heart failure with preserved ejection fraction and additive benefits when combined with SGLT2 inhibitors.
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
EP: 13.Steroidal vs Nonsteroidal MRAs in Heart Failure
EP: 14.Implementing MRAs for Heart Failure Treatment in the Clinic
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 the 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.
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