Protocol for Starting ACE Inhibitors and MRAs in Heart Failure with ACS
In patients with heart failure and acute coronary syndrome, ACE inhibitors should be initiated within 24 hours of presentation once hemodynamically stable (systolic BP >100 mmHg), starting with low doses and titrating upward, while MRAs should be added after stabilization in patients who remain symptomatic despite ACE inhibitor and beta-blocker therapy. 1
ACE Inhibitor Initiation Protocol
Timing and Patient Selection
- Start ACE inhibitors within the first 24 hours after acute myocardial infarction in hemodynamically stable patients with signs or symptoms of heart failure, even if transient 1, 2
- Initiate treatment after the acute phase once systolic blood pressure is ≥100 mmHg and the patient shows no signs of cardiogenic shock 2
- ACE inhibitors are indicated for all patients with reduced ejection fraction (EF ≤40-45%) following ACS, regardless of symptom severity 1
Starting Doses and Titration Schedule
Use these evidence-based starting doses: 1
- Captopril: 6.25 mg three times daily → target 50-100 mg three times daily
- Enalapril: 2.5 mg twice daily → target 10-20 mg twice daily
- Lisinopril: 2.5-5.0 mg once daily → target 20-35 mg once daily
- Ramipril: 2.5 mg once daily → target 5 mg twice daily or 10 mg once daily
- Trandolapril: 0.5-1.0 mg once daily → target 4 mg once daily
For patients with systolic BP <120 mmHg at baseline, reduce starting dose by 50% (e.g., lisinopril 2.5 mg) 2
Titration Strategy
- Double the dose at minimum 2-week intervals until target dose is achieved 1
- Aim for target doses proven effective in clinical trials, not symptom-based titration alone 1
- Higher doses reduce heart failure hospitalizations by 24% compared to low doses, though mortality benefit is modest 3, 4
- Some ACE inhibitor is better than no ACE inhibitor - use maximum tolerated dose if target cannot be reached 1
Monitoring Requirements
Check the following parameters: 1
- Before initiation: baseline blood pressure, serum creatinine, potassium, and BUN
- 1-2 weeks after each dose increase: recheck BP, creatinine, and potassium
- At 3 months, then every 6 months during maintenance therapy
- More frequently in patients with baseline renal dysfunction or electrolyte abnormalities
Acceptable Laboratory Changes
Do not stop or reduce ACE inhibitor for: 1
- Creatinine increase up to 50% above baseline OR up to 266 μmol/L (3 mg/dL), whichever is smaller
- Potassium up to 5.5 mmol/L
- eGFR ≥25 mL/min/1.73 m²
Reduce dose by 50% if: 1
- Creatinine increases >50% but <100% above baseline
- Potassium 5.5-6.0 mmol/L
- eGFR 20-25 mL/min/1.73 m²
Stop ACE inhibitor and seek specialist advice if: 1
- Potassium >5.5 mmol/L persists despite medication adjustment
- Creatinine increases >100% or >310 μmol/L (3.5 mg/dL)
- eGFR <20 mL/min/1.73 m²
- Symptomatic hypotension (systolic BP <90 mmHg for >1 hour) 2
Pre-Treatment Optimization
Before starting ACE inhibitors: 1, 5
- Review and reduce diuretic dose if no signs of congestion present
- Discontinue or reduce non-essential vasodilators (nitrates, calcium channel blockers)
- Stop nephrotoxic drugs (NSAIDs) if possible
- Avoid excessive diuresis in the 24 hours before initiation
MRA Initiation Protocol
Timing Relative to ACE Inhibitors
- Add MRA only after ACE inhibitor and beta-blocker are established and patient remains symptomatic 1, 6
- MRAs provide additional mortality benefit (37% reduction in CV death/HF hospitalization) when added to standard therapy 1
- In post-MI patients with HF, MRAs can be started 3-14 days after acute event once hemodynamically stable 1
Patient Selection for MRAs
Initiate MRA in patients with: 1
- NYHA class II symptoms with EF ≤30% (or ≤35% if QRS >130 ms) already on ACE inhibitor and beta-blocker
- NYHA class III-IV symptoms with EF ≤35% despite optimal medical therapy
- Post-MI with EF ≤40% and clinical heart failure or diabetes
Starting Doses
Use these evidence-based doses: 1
- Spironolactone: 25 mg once daily → target 25-50 mg once daily
- Eplerenone: 25 mg once daily → target 50 mg once daily
Critical Safety Monitoring for MRAs
Contraindications - do NOT start if: 1
- Serum creatinine >2.5 mg/dL (221 μmol/L)
- Baseline potassium >5.0 mmol/L
- eGFR <30 mL/min/1.73 m²
Monitor potassium and creatinine: 1, 5
- At 1 week after initiation
- At 1 month, then monthly for 3 months
- Every 3 months thereafter
- Whenever ACE inhibitor dose is increased
Stop MRA immediately if: 1
- Potassium >5.5 mmol/L
- Creatinine doubles or increases >3.0 mg/dL
Common Pitfalls and How to Avoid Them
Hypotension Management
- Asymptomatic low blood pressure does not require treatment change 1
- If symptomatic hypotension occurs, reduce diuretic dose first before reducing ACE inhibitor 1
- Consider reducing non-essential vasodilators before stopping ACE inhibitor 1
Cough
- ACE inhibitor-induced cough rarely requires discontinuation 1
- First exclude pulmonary edema as cause of new/worsening cough 1
- Only switch to ARB if cough is proven due to ACE inhibitor (recurs after withdrawal and rechallenge) and severely impacts quality of life 1
Renal Function Deterioration
- Some rise in creatinine and potassium is expected and acceptable 1
- Before adjusting ACE inhibitor, stop nephrotoxic drugs (NSAIDs), potassium supplements, and potassium-sparing diuretics (amiloride, triamterene) 1
- Reduce diuretic dose if no signs of congestion present 1
- It is very rarely necessary to stop an ACE inhibitor - seek specialist advice before discontinuation as clinical deterioration is likely 1
Combination Therapy Risks
- Never combine ACE inhibitor + ARB + MRA due to excessive risk of hyperkalemia and renal dysfunction 6
- Close monitoring is mandatory when combining ACE inhibitor with MRA 1
Post-ACS Specific Considerations
- In the GISSI-3 trial, 9% of STEMI patients developed persistent hypotension and 2.4% developed renal dysfunction with early ACE inhibitor use 2
- Despite these risks, early ACE inhibitor use saves 11 lives per 1000 STEMI patients treated 7
- Benefits are greater with longer treatment duration - continue indefinitely after MI 7