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

When to Avoid ACE Inhibitors

ACE inhibitors should be avoided in patients with a history of angioedema, pregnancy, bilateral renal artery stenosis, hyperkalemia >5.5 mEq/L, severe hypotension (systolic BP <80 mmHg), or markedly elevated serum creatinine (>3 mg/dL). 1, 2

Absolute Contraindications

• History of angioedema with previous ACE inhibitor use: This reaction can be life-threatening and justifies permanent avoidance of all ACE inhibitors 2, 1
• Pregnancy: ACE inhibitors are teratogenic and should be avoided in pregnant women or those planning to become pregnant 2, 1
• Bilateral renal artery stenosis: ACE inhibitors can cause acute renal failure in these patients due to their effect on efferent arteriolar vasodilation 1, 3
• Unilateral renal artery stenosis in patients with a single kidney: This represents the same physiological risk as bilateral stenosis 3

Relative Contraindications and Cautions

Renal Considerations

• Markedly elevated serum creatinine (>3 mg/dL): Risk of worsening renal function 2, 1
• Acute renal failure: Temporarily discontinue ACE inhibitors while precipitating factors are corrected 2
• Volume depletion: Can exacerbate hypotension and worsen renal function 2

Cardiovascular Considerations

• Severe hypotension (systolic BP <80 mmHg): ACE inhibitors may cause further dangerous hypotension 2, 1
• Cardiogenic shock: ACE inhibitors should not be initiated in patients at immediate risk of cardiogenic shock 2, 1

Electrolyte Abnormalities

• Elevated serum potassium (>5.5 mEq/L): Increased risk of dangerous hyperkalemia 2, 1
• Concomitant use with potassium-sparing diuretics: Increases risk of hyperkalemia, especially in patients with diabetes or chronic renal failure 2

Medication Interactions

• Combination with ARBs or direct renin inhibitors: Increased risk of adverse events including hyperkalemia, syncope, and acute kidney injury 2, 4
• NSAIDs: Can block the favorable effects and enhance adverse effects of ACE inhibitors 2

Special Populations at Higher Risk

• African Americans: Higher incidence of angioedema with ACE inhibitor use 2, 5
• Patients with diabetes mellitus: Increased risk of hyperkalemia 2, 4
• Elderly patients: May be more susceptible to hypotension and renal effects 5
• Patients with history of drug rash or seasonal allergies: Higher risk of angioedema 5

Management of Common Adverse Effects

Angioedema

• Occurs in <1% of patients but more frequently in Black patients 2
• If angioedema develops, permanently discontinue ACE inhibitors 6, 1
• ARBs are not reliably safe alternatives after ACE inhibitor-induced angioedema, with approximately 32% of patients experiencing recurrence 7, 2

Cough

• Occurs in 5-10% of White patients and up to 50% in Chinese patients 2, 1
• If cough is mild, continue therapy; if persistent and troublesome, consider switching to an ARB 2, 4

Hyperkalemia

• Monitor potassium levels, especially in patients with diabetes, chronic kidney disease, or those taking potassium supplements 2, 1
• Avoid combination with potassium-sparing diuretics when possible 2

Hypotension and Renal Insufficiency

• Consider reducing diuretic dose if hypotension occurs 2, 1
• Mild to moderate azotemia may be tolerated to maintain ACE inhibitor therapy 2
• Monitor renal function within 1-2 weeks of initiation and after dose increases 1, 4

Monitoring Recommendations

• Renal function: Check before starting therapy, 1-2 weeks after each dose increment, and every 3-6 months during maintenance 1, 4
• Potassium levels: Monitor before initiation, within 1-2 weeks of starting therapy, and periodically thereafter 2, 1
• Blood pressure: Assess regularly, especially in patients at risk for hypotension 2, 4

By carefully considering these contraindications and implementing appropriate monitoring, clinicians can safely prescribe ACE inhibitors to appropriate patients while minimizing adverse effects.