Under 2025 CCS/CHFS guidance, eligible patients with symptomatic heart failure with non-reduced ejection fraction should receive a mineralocorticoid receptor antagonist as standard early therapy, alongside an SGLT2 inhibitor. The main established payoff is fewer heart-failure hospitalizations, not a proven mortality reduction.

Why It Matters To Your Practice

• The guidance defines HFnrEF as LVEF greater than 40% and treats MRAs as standard therapy rather than a late add-on after diuretics or SGLT2 inhibitors fail.

• This is a different evidence profile from HFrEF, where spironolactone and eplerenone have more firmly established reductions in hospitalization, cardiovascular death, and all-cause death.

Clinical Implications

• The guideline does not require sequencing MRAs before SGLT2 inhibitors. “First-line” means early use in eligible symptomatic patients, alongside management of congestion and comorbidities.

• Loop diuretics remain important for symptom relief from congestion, but they do not replace therapies intended to reduce heart-failure hospitalization risk, including MRAs in HFnrEF as outlined by CCS/CHFS guidance and trials such as FINEARTS-HF and TOPCAT discussed in the evidence base.

Insights

• In the CCS/CHFS analysis, MRA therapy was associated with fewer heart-failure hospitalizations, with no established reduction in cardiovascular death; average improvement in patient-reported health status was small and not clinically significant.

• An individual-patient-data analysis of major trials similarly found a clearer survival benefit in HFrEF than in mildly reduced or preserved EF, where hospitalization benefit was seen but mortality estimates did not establish benefit conclusively. FINEARTS-HF showed benefit in LVEF 40% or greater mainly through fewer worsening-heart-failure events, while TOPCAT reduced heart-failure hospitalization without a significant reduction in its primary composite outcome alone. Mechanistically, MRAs may help through modest potassium-sparing natriuresis and effects on remodeling, fibrosis, and inflammation, but outcome trials have not established how much each pathway matters clinically. Aldo-DHF improved a diastolic-function surrogate without improving exercise capacity or quality of life.

The Bottom Line

• For symptomatic HFnrEF, MRAs are supported as early standard therapy when patients are eligible, but clinicians should frame expectations around hospitalization reduction rather than proven survival benefit.

• Eligibility and follow-up matter: avoid initiation when potassium is above 5.0 mmol/L, when eGFR is below 30 mL/min/1.73 m² for spironolactone or eplerenone, or below 25 mL/min/1.73 m² for finerenone, and recheck creatinine and potassium within one week of starting or dose change. The guidance does not specifically address patients whose EF has improved above 40% from previously reduced levels and says treatment should not be changed solely because current EF now meets the HFnrEF threshold.

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