mineralocorticoid receptor antagonists
3 min read
Updated 2026-03-15
Contents
mineralocorticoid receptor antagonists
Aldosterone antagonists at the collecting duct. GDMT for long-term mortality in HFrEF (RALES: 30% mortality reduction). But not an acute diuretic — ATHENA-HF (2017): high-dose spironolactone 100 mg showed no acute decongestion benefit. The benefit is antifibrotic, not diuretic.
mechanism
Block mineralocorticoid receptor → inhibit ENaC and Na⁺/K⁺-ATPase expression in collecting duct. Genomic mechanism → slow onset (24–48h spironolactone; full effect 48–72h). Weak diuretic (~2% filtered Na⁺). Mortality benefit is from antifibrotic/anti-remodelling effects.
comparison
| Spironolactone | Eplerenone | Finerenone | |
|---|---|---|---|
| Class | Steroidal | Steroidal | Non-steroidal |
| HFrEF dose | 25–50 mg daily | 25–50 mg daily | — (no HFrEF indication yet) |
| HFpEF dose | — | — | 10–20 mg daily |
| DKD dose | — | — | 10–20 mg daily |
| Cirrhosis dose | Up to 400 mg daily | — | — |
| MR selectivity | Non-selective (binds androgen/progesterone receptors) | Selective | Highly selective |
| Gynaecomastia | 10–15% | No | No |
| Diuretic effect | Weak | Weak | Minimal (non-steroidal → different MR conformational change) |
| Half-life | 16–23h (canrenone) | 4–6h | 2–3h |
| Key trials | RALES (severe HFrEF) | EMPHASIS-HF (mild HFrEF), EPHESUS (post-MI) | FIDELIO-DKD, FIGARO-DKD (DKD), FINEARTS-HF (HFmrEF/HFpEF) |
key points
- Not an acute diuretic — do not dose-escalate in ADHF expecting rapid decongestion. Start as GDMT during admission, at standard doses
- Check K⁺ and Cr at 1–2 weeks after starting or dose change — hyperkalaemia kills
- Avoid if K⁺ > 5.0 or eGFR < 30 (relative) / < 15 (absolute)
- The triple threat: MRA + ACEi/ARB + NSAID → dangerous hyperkalaemia
- Switch to eplerenone if gynaecomastia develops (the only reason to prefer it beyond cost)
- Finerenone is not interchangeable with spironolactone/eplerenone — different indication (DKD, HFpEF), minimal diuretic effect, no HFrEF mortality data. It is an anti-inflammatory/antifibrotic agent that happens to block MR, not a diuretic
- Finerenone: start 10 mg if eGFR 25–59, start 20 mg if eGFR ≥ 60; K⁺ must be ≤ 4.8 at initiation
- Cirrhosis is different: secondary hyperaldosteronism → spironolactone up to 400 mg/day is the backbone (not an adjunct)
adverse effects
- Hyperkalaemia — the major safety concern; worse with CKD + ACEi/ARB
- Gynaecomastia, breast tenderness, menstrual irregularities (spironolactone only — anti-androgen)
- AKI (pre-renal, especially triple therapy)
evidence
- RALES (1999) — spironolactone 25 mg in severe HFrEF: 30% mortality reduction (NNT ≈ 9)
- EMPHASIS-HF (2011) — eplerenone in mild HFrEF: reduced death + HF hospitalisation (HR 0.63)
- ATHENA-HF (2017) — spironolactone 100 mg in ADHF: no acute benefit at 96h
- FIDELIO-DKD (2020) — finerenone in T2DM + CKD: reduced kidney composite (HR 0.82) and CV events
- FIGARO-DKD (2021) — finerenone in T2DM + CKD (broader population): reduced CV composite (HR 0.87)
- FINEARTS-HF (2024) — finerenone in HFmrEF/HFpEF: reduced HF events (worsening HF + CV death composite); no mortality benefit