What is the appropriate starting dose and management of Angiotensin-Converting Enzyme (ACE) inhibitors for patients with hypertension or heart failure?

ACE Inhibitor Dosing and Management

Starting Doses

For heart failure with reduced ejection fraction (HFrEF), initiate ACE inhibitors at low doses and titrate upward to evidence-based target doses that have been proven to reduce mortality and hospitalizations. 1

Heart Failure Starting Doses:

• Captopril: 6.25 mg three times daily 1
• Enalapril: 2.5 mg twice daily 1
• Lisinopril: 2.5-5 mg once daily 1
• Ramipril: 1.25-2.5 mg once daily 1
• Trandolapril: 1 mg once daily 1

Hypertension Starting Doses:

• Lisinopril: 10 mg once daily 2
• Reduce to 5 mg once daily if patient is already on diuretics 2

Target Doses

Aim for the target doses used in clinical trials, as higher doses significantly reduce the combined endpoint of death and hospitalization compared to lower doses. 1, 3

Heart Failure Target Doses:

• Captopril: 50 mg three times daily (up to 100 mg three times daily) 1
• Enalapril: 10-20 mg twice daily 1
• Lisinopril: 30-35 mg once daily 1, 4
• Ramipril: 5 mg twice daily or 10 mg once daily 1
• Trandolapril: 4 mg once daily 1

Hypertension Target Doses:

• Lisinopril: 20-40 mg once daily 2

Titration Protocol

Double the dose at intervals of not less than 2 weeks if the lower dose has been well tolerated. 1

• Continue uptitration until target dose is reached, regardless of symptomatic response 1
• If target dose cannot be achieved, use the highest tolerated dose—some ACE inhibitor is better than none 1
• The ATLAS trial demonstrated that high-dose lisinopril (32.5-35 mg daily) reduced death or hospitalization by 12% and heart failure hospitalizations by 24% compared to low doses (2.5-5 mg daily) 3

Monitoring Requirements

Check renal function (creatinine, BUN) and serum potassium within 1-2 weeks of initiation and after each dose increase. 1

Acceptable Laboratory Changes:

• Creatinine increase: Up to 50% above baseline OR up to 3 mg/dL (266 μmol/L), whichever is greater 1, 4
• Potassium: Up to 5.5-6.0 mEq/L is acceptable 1

Ongoing Monitoring:

• Recheck at 3 months, then every 6 months 4
• Monitor blood pressure at each visit 1

Contraindications and Cautions

Absolute Contraindications:

• History of angioedema with ACE inhibitors 1
• Pregnancy or planning pregnancy 1

Exercise Caution (Seek Specialist Advice):

• Systolic blood pressure <80-90 mm Hg 1
• Creatinine >3 mg/dL (>221-266 μmol/L) 1
• Bilateral renal artery stenosis 1
• Potassium >5.0 mEq/L 1

Problem Management

Asymptomatic Hypotension:

• No action required—asymptomatic low blood pressure does not necessitate dose adjustment 1

Symptomatic Hypotension:

• Review and reduce doses of nitrates, calcium channel blockers, or other vasodilators 1
• If no signs of congestion, consider reducing diuretic dose 1
• If measures fail, seek specialist advice 1

Worsening Renal Function:

• Small increases in creatinine and potassium are expected and acceptable 1
• Stop concomitant nephrotoxic drugs (NSAIDs) if creatinine rises excessively 1
• If creatinine increases beyond acceptable limits, reduce ACE inhibitor dose or seek specialist consultation 1

Cough:

• ACE inhibitor-induced cough rarely requires discontinuation 1
• First exclude pulmonary edema as the cause 1
• Only switch to an angiotensin receptor blocker if cough is severe (e.g., preventing sleep) and proven to be ACE inhibitor-related through withdrawal and rechallenge 1

Special Populations

Post-Myocardial Infarction:

• Initiate within 24 hours in hemodynamically stable patients 1
• Lisinopril: 5 mg initially, then 5 mg at 24 hours, 10 mg at 48 hours, then 10 mg daily 1
• Start with 2.5 mg if systolic BP is 100-120 mm Hg 1, 2
• Continue for at least 6 weeks 1

Renal Impairment:

• Start with lower doses (2.5 mg lisinopril if GFR <30 mL/min) 2, 5
• Titrate cautiously with close monitoring 5

Key Clinical Pearls

• Never abruptly withdraw ACE inhibitors—this can lead to clinical deterioration 1
• All ACE inhibitors appear equally effective for heart failure and hypertension 1
• ACE inhibitors should be used together with beta-blockers in heart failure unless contraindicated 1
• Target doses from clinical trials should be the goal, as they provide superior outcomes compared to lower doses 1, 3