What is the recommended dosage of ACE (Angiotensin-Converting Enzyme) inhibitors, such as lisinopril, for the treatment of hypertension or heart failure?

ACE Inhibitor Dosing for Hypertension and Heart Failure

For hypertension, start lisinopril at 10 mg once daily and titrate to a target of 20-40 mg daily; for heart failure, start at 2.5-5 mg once daily and aggressively titrate to the target dose of 30-35 mg daily, as higher doses significantly reduce mortality and hospitalizations. 1, 2, 3

Hypertension Dosing

• Initial dose: 10 mg once daily in treatment-naive patients 1, 2
• Initial dose: 5 mg once daily if patient is already on diuretics 1
• Titrate at 2-week intervals based on blood pressure response 2, 1
• Target maintenance dose: 20-40 mg once daily 4, 1
• Doses up to 80 mg have been studied but provide no additional benefit 1

Heart Failure Dosing

The evidence strongly supports aggressive up-titration to high doses in heart failure patients:

• Initial dose: 5 mg once daily when used with diuretics and digoxin 1, 4
• Initial dose: 2.5 mg once daily if hyponatremia present (serum sodium <130 mEq/L) 1, 3
• Target dose: 30-35 mg once daily 2, 3, 4
• Maximum dose: 40 mg once daily 1, 4

Critical Evidence on Dose-Response

The ATLAS trial definitively demonstrated that high doses (32.5-35 mg daily) are superior to low doses (2.5-5 mg daily) in heart failure patients: 5, 6

• 12% reduction in death or hospitalization (p=0.002) 5, 3
• 24% reduction in heart failure hospitalizations (p=0.002) 5, 6
• 8% reduction in all-cause mortality (p=0.128, not statistically significant but clinically meaningful) 5

Common pitfall: Many clinicians fail to titrate to target doses and leave patients on subtherapeutic doses of 5-10 mg daily, missing substantial clinical benefits 3, 5

Post-Myocardial Infarction Dosing

For hemodynamically stable patients within 24 hours of MI: 1, 3

• Day 1: 5 mg orally
• Day 2: 5 mg
• Day 3: 10 mg
• Maintenance: 10 mg once daily for at least 6 weeks
• If low systolic BP (100-120 mmHg): Start with 2.5 mg 1

Renal Dose Adjustments

• CrCl >30 mL/min: No adjustment needed 1
• CrCl 10-30 mL/min: Start at half the usual dose (hypertension: 5 mg; heart failure: 2.5 mg) 1
• CrCl <10 mL/min or hemodialysis: Start at 2.5 mg once daily 1

Monitoring Protocol

Initial monitoring (critical for safety): 2, 3

• Check renal function and potassium 1-2 weeks after initiation 4, 2
• Recheck 1-2 weeks after each dose increase 2, 3
• Monitor at 3 months, then every 6 months 2, 3

Acceptable laboratory changes during titration: 2, 3

• Creatinine increase up to 50% above baseline OR to 3 mg/dL (whichever is greater) is acceptable 2, 3
• Potassium up to 5.5 mEq/L is generally manageable 4

Titration Strategy

The key principle: Titrate to target dose, not to symptomatic response 4

• Double the dose every 2 weeks if tolerated 4, 2
• Aim for target doses proven in clinical trials (30-35 mg for heart failure, 20-40 mg for hypertension) 4, 2
• If target dose not tolerated, use the highest tolerated dose 4, 3
• Small differences exist between intermediate and high doses, but low doses are clearly inferior 5

Important Precautions

Avoid during titration: 3

• NSAIDs and COX-2 inhibitors (worsen renal function and reduce efficacy) 3
• Potassium-sparing diuretics unless specifically needed for persistent hypokalemia 3

Cautions requiring specialist consultation: 4

• Systolic BP <80 mmHg 4
• Serum creatinine >3 mg/dL at baseline 4
• Bilateral renal artery stenosis 4
• Serum potassium >5.0 mEq/L at baseline 4

Absolute contraindications: 4

• History of angioedema with ACE inhibitors 4
• Pregnancy or planning pregnancy 4

Managing Adverse Effects

ACE inhibitor-induced cough: 3

• Rarely requires discontinuation 3
• Only switch to ARB if cough is proven ACE inhibitor-related through withdrawal and rechallenge 3

Hypotension during titration: 4

• Increase diuretic dose if signs of congestion present 4
• Temporary dose reduction acceptable, then retry up-titration 1
• Hypotension after initial dose does not preclude further titration 1