What is the recommended dosing for Lisinopril (Angiotensin-Converting Enzyme inhibitor) in patients with hypertension or heart failure?

Lisinopril Dosing Recommendations

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, adjusting at intervals of at least 2 weeks. 1

• The FDA-approved starting dose is 10 mg once daily in adults not taking diuretics 1
• If patients are already on diuretics, reduce the starting dose to 5 mg once daily 1
• The usual dosage range is 20-40 mg per day administered as a single daily dose 1
• Doses up to 80 mg have been used but do not provide greater antihypertensive effect 1
• If blood pressure remains uncontrolled on lisinopril alone, add a low-dose diuretic such as hydrochlorothiazide 12.5 mg 1

Heart Failure

For heart failure, start lisinopril at 2.5-5 mg once daily and titrate aggressively to the target dose of 30-35 mg once daily, as higher doses significantly reduce mortality and hospitalizations. 2, 3, 4

Starting Dose

• Begin with 5 mg once daily when used with diuretics and digitalis 1
• In patients with hyponatremia (serum sodium <130 mEq/L), start at 2.5 mg once daily 1
• The European Society of Cardiology recommends starting at 2.5-5.0 mg once daily 2

Target Dose

• The evidence-based target dose is 30-35 mg once daily 2, 3, 4
• The ATLAS trial demonstrated that high doses (32.5-35 mg daily) reduced hospitalizations for heart failure by 24% and the combined endpoint of death or hospitalization by 12% compared to low doses (2.5-5 mg daily) 4, 5
• Maximum dose is 40 mg once daily 1

Critical Pitfall

• Many clinicians fail to titrate to target doses, leaving patients undertreated 4
• Always aim for the target dose of 30-35 mg daily or the highest tolerated dose 3, 4
• The appearance of hypotension after the initial dose does not preclude subsequent careful dose titration 1

Post-Myocardial Infarction

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

• 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 daily 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

Monitoring Requirements

Check blood pressure, renal function, and electrolytes (particularly potassium) at baseline, 1-2 weeks after each dose increment, at 3 months, and then every 6 months. 3, 4

• During initial titration, check serum potassium and creatinine after 5-7 days of starting therapy and recheck every 5-7 days until values are stable 4
• An increase in creatinine up to 50% above baseline, or to 3 mg/dL (whichever is greater), is acceptable 3, 4
• Adjust diuretic doses to minimize hypovolemia, which may contribute to hypotension 1

Renal Impairment Dosing

For patients with creatinine clearance 10-30 mL/min, reduce the initial dose by half; for those on hemodialysis or creatinine clearance <10 mL/min, start at 2.5 mg once daily. 1

• No dose adjustment needed if creatinine clearance >30 mL/min 1
• For creatinine clearance 10-30 mL/min: start hypertension at 5 mg, heart failure at 2.5 mg, acute MI at 2.5 mg 1
• For hemodialysis or creatinine clearance <10 mL/min: start at 2.5 mg once daily 1
• Titrate upward as tolerated to a maximum of 40 mg daily 1
• Seek specialist advice before initiating lisinopril in patients with significant renal dysfunction 3

Important Drug Interactions and Precautions

• Avoid NSAIDs and COX-2 inhibitors, as they worsen renal function and reduce ACE inhibitor efficacy 4
• Avoid potassium-sparing diuretics during initiation unless specifically needed for persistent hypokalemia 4
• ACE inhibitor-induced cough rarely requires discontinuation; only switch to an ARB if cough is proven ACE inhibitor-related through withdrawal and rechallenge 4