When should Angiotensin-Converting Enzyme (ACE) inhibitors be used?

When to Use ACE Inhibitors

ACE inhibitors should be used as first-line therapy in patients with reduced left ventricular systolic function (ejection fraction <40-45%) with or without symptoms, hypertension with compelling indications (diabetes, chronic kidney disease), post-myocardial infarction, and symptomatic heart failure to reduce morbidity and mortality. 1

Primary Indications for ACE Inhibitor Therapy

Heart Failure

• Heart Failure with Reduced Ejection Fraction (HFrEF):

  • First-line therapy for all patients with LVEF ≤40-45%, with or without symptoms 1
  • Should be given as initial therapy in the absence of fluid retention 1
  • In patients with fluid retention, combine with diuretics 1
  • Titrate to doses shown effective in clinical trials, not just for symptom improvement 1

• Post-Myocardial Infarction:

  • Initiate in patients with signs or symptoms of heart failure after acute MI, even if symptoms are transient 1
  • Start within 24 hours of symptom onset in hemodynamically stable patients 2

Hypertension

• Hypertension with Compelling Indications:

  • Diabetes mellitus 1
  • Chronic kidney disease 1
  • Left ventricular dysfunction 1
  • Post-myocardial infarction 1

• General Hypertension:

  • Consider as one of the first-line options along with beta-blockers and diuretics 3
  • Initial dose typically 5-10 mg once daily, titrated to 20-40 mg daily as needed 2, 4

Asymptomatic Left Ventricular Dysfunction

• Treat to delay or prevent development of heart failure 1
• Reduces risk of myocardial infarction and sudden death 1

Diabetic Nephropathy

• Recommended for patients with diabetes to reduce risk of nephropathy progression 1, 5
• Particularly beneficial in patients with albuminuria 1

Dosing and Monitoring

Initiation and Titration

1. Start with low doses and titrate upward to target doses used in clinical trials 1, 6
2. Monitoring schedule:
   • Before starting therapy
   • 1-2 weeks after each dose increment
   • At 3-6 months interval
   • More frequent monitoring for patients with renal dysfunction 1, 6

Special Populations

• Renal impairment:

  • For creatinine clearance 10-30 mL/min: reduce initial dose by half 2, 4
  • For creatinine clearance <10 mL/min or hemodialysis: start with 2.5 mg 2
  • Regular monitoring of renal function is essential 1, 6

• Patients on diuretics:

  • Consider discontinuing diuretic 2-3 days before starting ACE inhibitor 4
  • If diuretic cannot be discontinued, start with lower dose (2.5 mg) under medical supervision 4

Contraindications and Precautions

Absolute Contraindications

• Bilateral renal artery stenosis 1
• Previous angioedema with ACE inhibitor therapy 1
• Pregnancy 1

Adverse Effects to Monitor

1. Common side effects:

   • Cough (up to 20% of patients) 1, 7
   • Hypotension, especially with first dose 1, 8
   • Renal insufficiency 1, 5
   • Hyperkalemia 1

2. Rare but serious:

   • Angioedema (more frequent in Black patients and women) 1, 7
   • Acute renal failure (in patients with critical dependence on angiotensin II for glomerular filtration) 5

Drug Interactions

• Use with caution when combined with:
  • Potassium supplements
  • Potassium-sparing diuretics
  • NSAIDs (can reduce efficacy and worsen renal function) 6

Alternative Options

• Angiotensin Receptor Blockers (ARBs):

  • Effective alternative for patients who develop cough or angioedema on ACE inhibitors 1
  • May have similar efficacy but fewer adverse events compared to ACE inhibitors 7

• For Heart Failure:

  • Consider newer agents like ARNI (Angiotensin Receptor-Neprilysin Inhibitor) which may be superior to ACE inhibitors in certain patients 1, 6
  • Quadruple therapy with ARNI, beta-blocker, MRA, and SGLT2i provides the largest reduction in cardiovascular events 6

Practical Approach to ACE Inhibitor Use

1. Identify appropriate candidates based on indications above
2. Check baseline labs: renal function, electrolytes
3. Start with low dose and titrate gradually to target dose
4. Monitor closely after initiation and dose increases
5. Adjust other medications as needed (especially diuretics)
6. Educate patients about potential side effects and when to seek medical attention

ACE inhibitors remain a cornerstone therapy for cardiovascular disease management due to their proven mortality and morbidity benefits, particularly in heart failure and post-myocardial infarction patients.