What is the starting dose of lisinopril (angiotensin-converting enzyme inhibitor) for hypertension and heart failure?

Starting Dose of Lisinopril

For hypertension, start lisinopril at 10 mg once daily; for heart failure, start at 5 mg once daily (or 2.5 mg once daily if the patient has hyponatremia with serum sodium <130 mEq/L or is at high risk for hypotension). 1

Hypertension Dosing

• The FDA-approved starting dose for hypertension is 10 mg once daily 1
• If the patient is already on diuretics, reduce the starting dose to 5 mg once daily to minimize risk of symptomatic hypotension 1
• Titrate upward based on blood pressure response at intervals of not less than 2 weeks 2, 3
• The usual maintenance range is 20-40 mg once daily, though doses up to 80 mg have been studied 1

Heart Failure Dosing

• Start at 5 mg once daily when used with diuretics and digitalis for systolic heart failure 1
• In patients with hyponatremia (serum sodium <130 mEq/L), start at 2.5 mg once daily 1
• The European Society of Cardiology guidelines recommend an initiating dose of 2.5 mg daily for all heart failure patients, with a target dose of 30-35 mg once daily 2, 4
• Titrate at intervals of not less than 2 weeks, doubling the dose each time as tolerated 2, 5
• Aim for the target dose of 30-35 mg daily—the ATLAS trial demonstrated that high doses (32.5-35 mg daily) reduce hospitalizations by 24% and the combined endpoint of death or hospitalization by 12% compared to low doses (2.5-5 mg daily) 4, 6

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 1
• If systolic blood pressure is ≤120 mmHg and >100 mmHg during the first 3 days post-infarct, start at 2.5 mg 1

Renal Impairment Adjustments

• No dose adjustment needed if creatinine clearance >30 mL/min 1
• If creatinine clearance is 10-30 mL/min, reduce the initial dose by half: 5 mg for hypertension, 2.5 mg for heart failure 1, 7, 8
• For hemodialysis patients or creatinine clearance <10 mL/min, start at 2.5 mg once daily 1

Critical Monitoring During Initiation

• Check serum potassium and creatinine after 5-7 days of starting therapy, then recheck every 5-7 days during titration until values are stable 2, 4
• Monitor blood pressure, renal function, and electrolytes 1-2 weeks after each dose increment, at 3 months, then every 6 months 2, 4
• An increase in creatinine up to 50% above baseline, or to 3 mg/dL (whichever is greater), is acceptable and does not require discontinuation 4, 5

Common Pitfalls to Avoid

• Many clinicians fail to titrate to target doses in heart failure—this is a critical error, as the ATLAS trial clearly showed superior outcomes with higher doses 4, 6
• Asymptomatic hypotension does not require dose reduction or treatment changes 2
• Consider reducing or withholding diuretics for 24 hours before initiating lisinopril to minimize first-dose hypotension 2
• Avoid NSAIDs and COX-2 inhibitors, as they worsen renal function and reduce ACE inhibitor efficacy 4, 5
• Avoid potassium-sparing diuretics during initiation unless specifically needed for persistent hypokalemia 2, 4
• ACE inhibitor-induced cough rarely requires discontinuation—only switch to an angiotensin receptor blocker if cough is proven ACE inhibitor-related through withdrawal and rechallenge 2, 5

Key Principle

Remember: some ACE inhibitor is better than no ACE inhibitor—aim for target dose, but if not tolerated, use the highest tolerated dose 2, 5