What are the indications and usage of Angiotensin-Converting Enzyme (ACE) inhibitors?

Indications and Usage of ACE Inhibitors

ACE inhibitors are indicated for the treatment of hypertension, heart failure with reduced ejection fraction (HFrEF), and reduction of mortality in acute myocardial infarction, with proven benefits in reducing cardiovascular events and mortality across these conditions. 1, 2

Primary Indications

• Hypertension: ACE inhibitors are effective first-line agents for treating hypertension in adults and children over 6 years of age, lowering the risk of fatal and non-fatal cardiovascular events including strokes and myocardial infarctions 1
• Heart Failure: Recommended for all patients with HFrEF with current or prior symptoms to reduce mortality and hospitalization, unless contraindicated 2
• Post-Myocardial Infarction: Indicated for reduction of mortality in hemodynamically stable patients within 24 hours of acute myocardial infarction 1
• Diabetic Nephropathy: Particularly beneficial in patients with type 1 diabetic nephropathy and may be beneficial in type 2 diabetic nephropathy 2

Specific Patient Populations

• Hypertensive Patients with Diabetes: ACE inhibitors are preferred agents for patients with diabetes to achieve target blood pressure <130/80 mmHg, offering renoprotective effects beyond blood pressure control 2
• Patients with Left Ventricular Dysfunction: Strongly indicated for patients with left ventricular dysfunction with or without symptomatic heart failure 2
• Patients ≥55 years with Cardiovascular Risk Factors: ACE inhibitors should be considered in patients over 55 years of age with hypertension or another cardiovascular risk factor (history of CVD, dyslipidemia, microalbuminuria, smoking) to reduce cardiovascular events 2

Dosing and Administration

• Treatment should be initiated at low doses and gradually increased if tolerated 2
• Common ACE inhibitors and their dosing ranges include:
  • Captopril: Initial 6.25 mg three times daily, maximum 50 mg three times daily 2
  • Enalapril: Initial 2.5 mg twice daily, maximum 10-20 mg twice daily 2
  • Lisinopril: Initial 2.5-5 mg once daily, maximum 20-40 mg once daily 2
  • Ramipril: Initial 1.25-2.5 mg once daily, maximum 10 mg once daily 2

Monitoring and Safety

• Renal function and serum potassium should be assessed within 1-2 weeks of initiation and periodically thereafter 2
• More frequent monitoring is needed in patients with:
  • Preexisting hypotension (systolic BP <80 mmHg) 2
  • Hyponatremia 2
  • Diabetes mellitus 2
  • Azotemia 2
  • Those taking potassium supplements 2

Contraindications and Cautions

• Absolute Contraindications:

  • History of angioedema with previous ACE inhibitor use 2
  • Pregnancy or planning pregnancy 2
  • Bilateral renal artery stenosis 2

• Use with Caution in:

  • Very low systemic blood pressure (systolic BP <80 mmHg) 2
  • Markedly increased serum creatinine (>3 mg/dL) 2
  • Elevated serum potassium (>5.0 mEq/L) 2
  • Peripheral vascular disease due to association with renovascular disease 2

Alternatives When ACE Inhibitors Cannot Be Used

• Angiotensin receptor blockers (ARBs) are recommended alternatives for patients who cannot tolerate ACE inhibitors due to cough or angioedema 2, 3
• ARBs have similar efficacy to ACE inhibitors in hypertension and heart failure but with fewer adverse effects such as cough 3, 4

Common Side Effects and Management

• Cough: Dry, persistent cough occurs in up to 20% of patients and is a common reason for discontinuation 2, 4
• Angioedema: Rare (<1%) but potentially life-threatening; more common in Black patients 2
• Hypotension: First-dose hypotension may occur, particularly in patients with heart failure or volume depletion 5
• Hyperkalemia: Monitor potassium levels, especially when combined with potassium-sparing diuretics 2
• Acute kidney injury: Particularly in patients with bilateral renal artery stenosis or severe volume depletion 2

Clinical Pearls

• Abrupt withdrawal of ACE inhibitors should be avoided as it can lead to clinical deterioration in heart failure patients 2
• When target doses cannot be achieved due to intolerance, intermediate doses should be used, as there are likely only small differences in efficacy between low and high doses 2
• The combination of ACE inhibitors with diuretics is particularly effective in hypertension management 6
• In patients with heart failure, ACE inhibitors should be used together with a beta-blocker unless contraindicated 2