Spironolactone in Acute Coronary Syndrome
Spironolactone should be initiated at 25 mg once daily in ACS patients who develop heart failure with LVEF ≤40% (or ≤35% depending on guideline), starting 3-14 days post-MI, provided serum potassium is ≤5.0 mEq/L and eGFR is >30 mL/min/1.73m². 1, 2
Specific Indications for Starting Spironolactone Post-ACS
The primary indication for spironolactone in ACS is when patients develop heart failure or left ventricular dysfunction following myocardial infarction. 1
Key criteria from EPHESUS trial (the landmark post-MI study):
- LVEF ≤40% 1
- Evidence of heart failure OR diabetes mellitus 1
- Initiation window: 3-14 days after acute MI 1
- Already on ACE inhibitor/ARB (87% of patients) and beta-blocker (75% of patients) 1
This resulted in a 15% relative risk reduction in mortality. 1
Dosing Protocol
Initial Dose
- Start with 25 mg once daily if potassium ≤5.0 mEq/L and eGFR >50 mL/min/1.73m² 3, 2
- For eGFR 30-50 mL/min/1.73m²: consider 12.5 mg once daily or 25 mg every other day 3, 2
- Do NOT start if potassium >5.0 mEq/L or eGFR <30 mL/min/1.73m² 3
Target Dose
- Increase to 50 mg once daily after 4 weeks if potassium remains ≤5.0 mEq/L and renal function is stable 1, 3
- For reduced renal function (eGFR 30-49): maintain at 12.5-25 mg once daily 3
Critical Monitoring Requirements
Initial Monitoring (Most Important)
- Check potassium and creatinine within 2-3 days after starting 3
- Recheck again at 7 days 3
- Then at 1,2,3, and 6 months, followed by every 6 months 1
This intensive early monitoring is crucial because real-world hyperkalemia rates (up to 24%) far exceed clinical trial rates (2%), particularly in elderly patients and those with renal dysfunction. 1, 4
Dose Adjustment Thresholds
- Potassium 5.5-6.0 mEq/L: Reduce dose by half (e.g., 25 mg every other day) 1, 2
- Potassium ≥6.0 mEq/L: Stop immediately and monitor closely; specific treatment may be needed 1
- Creatinine >2.5 mg/dL (220 μmol/L): Reduce dose by half 1
- Creatinine >3.5 mg/dL (310 μmol/L): Stop immediately 1
Essential Precautions in the ACS Setting
Mandatory Actions Before Starting
- Discontinue potassium supplements when initiating spironolactone 1, 3
- Counsel patients to avoid high-potassium foods and NSAIDs 1, 3
- Verify adequate renal function (eGFR ≥30 mL/min/1.73m²) 3
High-Risk Populations Requiring Extra Caution
Patients at increased risk for life-threatening hyperkalemia include: 4
- Age >70 years 4
- Baseline renal insufficiency 4
- Diabetes mellitus 4
- Risk for dehydration (common post-ACS with diuretic therapy) 4
- Concurrent medications causing hyperkalemia 4
In these high-risk patients, do not exceed 25 mg daily and monitor even more frequently. 4
Critical Drug Interaction
Avoid the routine triple combination of ACE inhibitor + ARB + spironolactone due to substantially increased hyperkalemia risk. 1, 3 Use spironolactone with either an ACE inhibitor OR ARB, not both. 1
Alternative Agent
Eplerenone (25 mg daily, titrating to 50 mg daily) is an alternative with similar efficacy but fewer anti-androgenic effects (gynecomastia occurs in 10% with spironolactone vs. minimal with eplerenone). 1, 3 Eplerenone was specifically studied in the post-MI population (EPHESUS trial) with the same dosing and monitoring requirements. 1
Common Pitfall to Avoid
The most dangerous pitfall is applying clinical trial results to unselected real-world patients without adequate monitoring. A population-based study in Ontario showed that after RALES publication, spironolactone prescriptions tripled, but hospitalizations for hyperkalemia increased from 2.4 to 11 per 1000 patients, with associated mortality rising from 0.3 to 2 per 1000. 1 This occurred because trial patients were highly selected with close monitoring, while real-world patients often have multiple comorbidities and less rigorous follow-up.
When NOT to Use Spironolactone in ACS
- No evidence of heart failure or LV dysfunction post-MI 1
- Baseline potassium >5.0 mEq/L 3, 2
- eGFR <30 mL/min/1.73m² 3
- Already on both ACE inhibitor AND ARB 1
- Inability to ensure close monitoring 1
Note: High-dose spironolactone (100 mg) in acute decompensated heart failure showed no benefit over usual care in the ATHENA-HF trial, so this strategy should not be used in the acute setting. 5