What is the recommended dosing of lisinopril (Angiotensin-Converting Enzyme (ACE) inhibitor) for adults with hypertension, heart failure, or impaired renal function?

Lisinopril Dosing for Adults

Hypertension

For hypertension, start lisinopril at 10 mg once daily and titrate to a usual maintenance dose of 20-40 mg once daily, with a maximum of 80 mg daily if needed. 1

• Initial dose: 10 mg once daily in most patients 1
• Diuretic-treated patients: Start at 5 mg once daily to minimize first-dose hypotension 1
• Target maintenance range: 20-40 mg once daily 1
• Maximum dose: 80 mg daily, though doses above 40 mg do not appear to provide significantly greater blood pressure reduction 1, 2

Dosing Strategy

• Adjust dose based on blood pressure response, typically at 2-week intervals 3
• If blood pressure remains uncontrolled on lisinopril alone, add a low-dose diuretic (e.g., hydrochlorothiazide 12.5 mg) rather than pushing lisinopril to maximum doses 1
• After adding a diuretic, you may be able to reduce the lisinopril dose 1

Heart Failure

For heart failure, start lisinopril at 2.5-5 mg once daily and titrate to a target dose of 20-35 mg once daily, with evidence supporting higher doses (32.5-35 mg) for superior outcomes. 3, 1, 4

• Initial dose: 5 mg once daily when used with diuretics and digitalis 1
• Hyponatremic patients (Na <130 mEq/L): Start at 2.5 mg once daily 1
• Target dose: The ATLAS trial demonstrated that high doses (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, 4
• Maximum dose: 40 mg once daily 1
• Recommended maintenance range: 5-20 mg daily per European guidelines, though higher doses show greater benefit 3, 4

Titration Protocol

• Double the dose at minimum 2-week intervals 3
• Aim for target dose or the highest tolerated dose 3
• Remember: some ACE inhibitor is better than no ACE inhibitor if target cannot be reached 3
• Hypotension after the initial dose does not preclude careful subsequent titration 1

Acute Myocardial Infarction

For hemodynamically stable patients within 24 hours of MI, give lisinopril 5 mg initially, followed by 5 mg at 24 hours, 10 mg at 48 hours, then 10 mg once daily for at least 6 weeks. 1

• Low systolic BP (100-120 mmHg): Start at 2.5 mg 1
• Hypotension (SBP ≤100 mmHg): Reduce maintenance to 5 mg daily with temporary reductions to 2.5 mg if needed 1
• Prolonged hypotension (SBP <90 mmHg for >1 hour): Withdraw lisinopril 1

Renal Impairment Dosing

Dose adjustment is required only when creatinine clearance falls below 30 mL/min. 1, 5, 6

• CrCl >30 mL/min: No dose adjustment needed 1
• CrCl 10-30 mL/min: Start at half the usual dose:
  • Hypertension: 5 mg daily 1
  • Heart failure: 2.5 mg daily 1
  • Post-MI: 2.5 mg daily 1
  • Titrate as tolerated to maximum 40 mg daily 1
• CrCl <10 mL/min or hemodialysis: Start at 2.5 mg once daily 1

Important Renal Considerations

• Lisinopril accumulates in severe renal failure but does not cause excessive antihypertensive effects 6
• A moderate dose of 10 mg daily is associated with hyperkalemia risk in patients with diabetes 3
• Monitor renal function and potassium within 1-2 weeks of initiation, with each dose increase, and at least yearly 3

Critical Monitoring Protocol

Check potassium, creatinine, and blood pressure at baseline, 5-7 days after initiation or dose changes, then at 3 months, and every 6 months thereafter. 3

Acceptable Changes During Titration

• Creatinine: Increases up to 50% above baseline or to 3 mg/dL (whichever is greater) are acceptable 7
• Potassium: Monitor closely; hyperkalemia risk increases with moderate-to-high doses, especially in diabetics 3

When to Reduce or Stop

• Creatinine rises 100% or exceeds 4 mg/dL: Halve the dose and seek specialist advice 7
• Hyperkalemia (K >5.0 mmol/L): Seek specialist advice 3
• Symptomatic hypotension: Reduce diuretic dose first before reducing lisinopril 3, 1

Critical Pitfalls to Avoid

• Do not stop for small creatinine rises: Clinical deterioration is likely if ACE inhibitors are withdrawn for minor renal function changes 7
• Avoid NSAIDs and COX-2 inhibitors: These worsen renal function and reduce ACE inhibitor efficacy 3, 7
• Avoid potassium-sparing diuretics during initiation: Risk of hyperkalemia 3
• Do not undertitrate: Higher doses provide superior outcomes in heart failure; push to target doses whenever possible 4
• Asymptomatic hypotension does not require dose adjustment: Only symptomatic hypotension warrants intervention 3
• Consider reducing or withholding diuretics 24 hours before initiation: This minimizes first-dose hypotension risk 3, 7