What is the recommended dosing for Lisinopril (angiotensin-converting enzyme inhibitor) in patients with hypertension or heart failure?

Lisinopril Dosing for Hypertension and Heart Failure

Hypertension

For hypertension, start lisinopril at 10 mg once daily and titrate to a usual maintenance dose of 20-40 mg once daily based on blood pressure response, with dose adjustments made at intervals of at least 2 weeks. 1

• The FDA-approved initial dose is 10 mg once daily in adults not taking diuretics 1
• If blood pressure is inadequately controlled on lisinopril alone, add a low-dose diuretic such as hydrochlorothiazide 12.5 mg 1
• For patients already on diuretics, start at 5 mg once daily to minimize risk of hypotension 1
• Doses up to 80 mg have been studied but do not appear to provide greater antihypertensive effect 1
• Titrate at intervals of not less than 2 weeks according to blood pressure response 2, 3

Heart Failure

For heart failure, start lisinopril at 2.5-5 mg once daily and aggressively titrate to the target dose of 30-35 mg once daily, as this higher dose significantly reduces mortality and hospitalizations compared to low doses. 4, 2, 5

Starting Dose

• Begin at 5 mg once daily when used with diuretics and digitalis 1
• Use 2.5 mg once daily in patients with hyponatremia (serum sodium <130 mEq/L) or low systolic blood pressure 1
• The European Society of Cardiology recommends initiating at 2.5 mg daily for all heart failure patients 4, 2

Target Dose - Critical Point

• The ATLAS trial demonstrated that high-dose lisinopril (32.5-35 mg daily) reduced the combined endpoint of death or hospitalization by 12% and heart failure hospitalizations by 24% compared to low doses (2.5-5 mg daily) 4, 5
• Target dose is 30-35 mg once daily, with maximum dose of 40 mg daily 2, 3, 1
• Many clinicians fail to titrate to target doses—this is a critical error as outcomes are dose-dependent 2
• Titrate upward every 5-7 days to 2 weeks as tolerated until target dose is achieved 4, 2

Post-Myocardial Infarction

In hemodynamically stable patients within 24 hours of acute MI, give 5 mg orally, then 5 mg after 24 hours, 10 mg after 48 hours, then 10 mg once daily for at least 6 weeks. 1, 2

• For patients with low systolic blood pressure (≤120 mmHg and >100 mmHg) during the first 3 days, start at 2.5 mg 1
• If hypotension occurs (systolic BP ≤100 mmHg), reduce to a maintenance dose of 5 mg with temporary reductions to 2.5 mg if needed 1
• Withdraw lisinopril if prolonged hypotension occurs (systolic BP <90 mmHg for more than 1 hour) 1

Renal Impairment Dosing

Adjust initial doses based on creatinine clearance, but do not avoid ACE inhibitors in patients with mild-to-moderate renal impairment. 1, 6

• No dose adjustment needed if creatinine clearance >30 mL/min 1
• For creatinine clearance 10-30 mL/min: reduce initial dose by half (hypertension: 5 mg; heart failure: 2.5 mg; acute MI: 2.5 mg), then titrate to maximum 40 mg daily 1
• For hemodialysis or creatinine clearance <10 mL/min: start at 2.5 mg once daily 1
• Overall glomerular filtration rate typically remains stable during treatment even in patients with baseline renal impairment 6

Monitoring Protocol

Check serum potassium and creatinine after 5-7 days of starting therapy, recheck every 5-7 days during titration until stable, then monitor at 1-2 weeks after each dose increment, at 3 months, and every 6 months thereafter. 4, 2, 3

Acceptable Changes

• An increase in creatinine up to 50% above baseline, or to 3 mg/dL (whichever is greater), is acceptable 2, 3
• If renal function deteriorates substantially beyond these parameters, stop treatment 4
• Serum potassium should remain ≤5.5 mmol/L 4

Critical Precautions

• Avoid NSAIDs and COX-2 inhibitors—they worsen renal function and reduce ACE inhibitor efficacy 4, 2
• Avoid potassium-sparing diuretics during initiation unless specifically needed for persistent hypokalemia despite ACE inhibition 4, 2
• Consider reducing or withholding diuretics for 24 hours before starting lisinopril to minimize hypotension risk 4
• Review need for and dose of other vasodilators before initiation 4

Common Pitfalls to Avoid

• Failure to titrate to target doses: The evidence clearly shows dose-dependent benefits, particularly in heart failure where 30-35 mg daily is the goal 4, 2, 5
• Premature discontinuation for cough: ACE inhibitor-induced cough rarely requires discontinuation; only switch to an ARB if cough is proven ACE inhibitor-related through withdrawal and rechallenge 2
• Excessive caution with blood pressure drops: The appearance of hypotension after the initial dose does not preclude subsequent careful dose titration following effective hypotension management 1
• Inadequate monitoring during titration: Electrolytes and renal function must be checked every 5-7 days during dose escalation 4, 2