MRAs for reduced ejection fraction
Spironolactone · eplerenone · where finerenone fits
These medicines block aldosterone, a hormone that promotes salt retention and heart damage. For reduced ejection fraction (HFrEF), spironolactone or eplerenone helps eligible patients live longer and avoid hospital stays. Finerenone is not an established replacement for these HFrEF treatments. [3] [6]
What benefit was seen?
Each trial added medicine or placebo to usual care. Different patients and follow-up prevent a fair drug ranking. [1] [2]
| Trial / outcome | Medicine | Placebo |
|---|---|---|
| RALES: death, mean 24 months | 284/822 (35%) | 386/841 (46%) [1] |
| EMPHASIS-HF: HF admission or heart-related death, median 21 months | 249/1,364 (18.3%) | 356/1,373 (25.9%) [2] |
That is about 11 fewer deaths per 100 in severe HFrEF with spironolactone, and 8 fewer composite events per 100 in milder HFrEF with eplerenone. Personal benefit may differ. [1] [2]
Commonly reported side effects
| Reported event | Medicine | Placebo |
|---|---|---|
| Spironolactone: breast enlargement/pain in men | 61/603 (10%) | 9/614 (1%) [1] |
| Eplerenone: high potassium | 109/1,360 (8%) | 50/1,369 (3.7%) [2] |
| Eplerenone: low blood pressure | 46/1,360 (3.4%) | 37/1,369 (2.7%) [2] |
Both can raise potassium or worsen kidney function. Eplerenone causes fewer hormone-related effects. Reported events are not all caused by medicine; these are trial-period, not yearly rates. [1] [2] [4] [5]
How often did people stop?
Adverse-event stopping: spironolactone 62/822 (8%) versus placebo 40/841 (5%); eplerenone permanent withdrawal 188/1,360 (13.8%) versus 222/1,369 (16.2%), over the trial periods above. [1] [2]
Potassium-related stopping was a smaller subset: serious high potassium with spironolactone 3/822 versus 1/841; permanent withdrawal with eplerenone 15/1,360 versus 12/1,369. [1] [2]
In a Swedish HFrEF prescription study, an estimated 29% had a refill-defined stop by one year; many restarted. This includes all reasons, not just side effects. Stopping medicine differs from leaving follow-up. [7]
One medicine, a blood-test plan
One MRA, scheduled blood tests. Start only when potassium is below 5.0 and kidney filtration (eGFR) is above 30. Spironolactone: check potassium within one week of starting or changing the dose. Eplerenone: check before starting, within one week and at one month. Continue regular checks even when you feel well. [4] [5] [3]
Check new medicines with your team, especially antibiotics, ibuprofen/naproxen, potassium supplements and potassium salt substitutes. Eplerenone can still raise potassium. It is not a safe substitute for spironolactone when potassium is high. [4] [5]
Call for dehydration, weakness, palpitations or breast changes. Fainting needs urgent assessment. Spironolactone is generally avoided in pregnancy. Contact your team promptly if pregnant or planning pregnancy. Do not change or stop treatment without contacting them. [4] [5]
What might I pay out of pocket?
| Drug / fill | GoodRx coupon | Blueberry cash |
|---|---|---|
| Spironolactone 25 mg ×30 | $9.73; Walgreens, ZIP 85001 | $11.87; $15.86 shipped [8] [11] [12] |
| Eplerenone 25 mg ×30 | Quote not verified | $15.69; $19.68 shipped [9] [11] [12] |
Blueberry estimates include nonmember fees; shipping adds $3.99. GoodRx is a cash coupon, not insurance; tax may apply. Prices and availability vary. [11] [12] [8]
Typical employer-plan tier 1/2/3 copays average $12/$40/$71 (KFF 2025, plans with 3+ tiers), not these drugs’ specific copays. [13]
Medicare 2026: plan-specific cost; deductible at most $615; $2,100 annual cap across covered Part D drugs, excluding premiums. Extra Help: generally up to $5.10 generic/$12.65 brand if eligible. Cash outside Part D does not count toward its deductible/cap. [14] [15] [16]