Maximum Dose of Lisinopril
The maximum dose of lisinopril is 40 mg once daily for both hypertension and heart failure, though doses up to 80 mg have been studied in hypertension without demonstrating additional benefit. 1
Target Dosing by Indication
Heart Failure
- Target dose: 30-35 mg once daily for optimal mortality and morbidity reduction 2, 3
- The ATLAS trial demonstrated that high-dose lisinopril (32.5-35 mg daily) reduced death or hospitalization by 12% and heart failure hospitalizations by 24% compared to low-dose therapy (2.5-5 mg daily) 2, 3, 4
- Starting dose: 5 mg once daily (or 2.5 mg if hyponatremic with serum sodium <130 mEq/L) 1
- Titrate upward at minimum 2-week intervals to reach target or maximum tolerated dose 2, 5
Hypertension
- Target dose: 20-40 mg once daily 1, 6
- Starting dose: 10 mg once daily (5 mg if on diuretics) 1
- Doses up to 80 mg have been used but provide no greater blood pressure reduction than 40 mg 1
Post-Myocardial Infarction
- Maximum dose: 10 mg once daily for at least 6 weeks 1
- Lower doses (2.5-5 mg) may be necessary if systolic blood pressure is low or hypotension develops 1
Titration Strategy
The key principle is to achieve the highest tolerated dose, as clinical benefit is dose-dependent. 2, 3
- Double the dose at each titration step, waiting at least 2 weeks between increases 2, 5
- Monitor blood pressure, serum creatinine, and potassium 5-7 days after each dose change 2, 5
- Continue monitoring at 3 months, then every 6 months during maintenance 3, 5
- Some ACE inhibitor is better than no ACE inhibitor—use the maximum tolerated dose even if target cannot be reached 2, 5
Acceptable Changes During Titration
Renal Function
- Creatinine increase up to 50% above baseline or to 3 mg/dL (266 μmol/L), whichever is greater, is acceptable 2, 5
- If creatinine rises beyond these limits, halve the lisinopril dose and recheck labs 2
- Discontinue nephrotoxic drugs (NSAIDs, non-essential vasodilators) before reducing lisinopril 2, 5
Potassium
- Potassium up to 5.5 mmol/L is acceptable 2
- If potassium rises to 6.0 mmol/L, halve the dose and seek specialist advice 2
- Stop potassium supplements and potassium-sparing diuretics if hyperkalemia develops 2
Blood Pressure
- Asymptomatic hypotension does not require dose adjustment 2, 5
- For symptomatic hypotension, reduce diuretic dose first before lowering lisinopril 2
- Only reduce lisinopril if hypotension persists after optimizing other medications 2
Renal Dose Adjustments
- No adjustment needed if creatinine clearance >30 mL/min 1
- CrCl 10-30 mL/min: Start at half the usual dose (hypertension 5 mg, heart failure 2.5 mg), titrate to maximum 40 mg daily 1
- CrCl <10 mL/min or hemodialysis: Start at 2.5 mg once daily 1
Critical Pitfalls to Avoid
- Never combine with NSAIDs or COX-2 inhibitors—they worsen renal function and reduce ACE inhibitor efficacy 5
- Do not discontinue lisinopril for asymptomatic lab changes without attempting dose reduction first 2
- Avoid potassium-sparing diuretics during initiation due to hyperkalemia risk 5
- Clinical deterioration is likely if ACE inhibitor is withdrawn—seek specialist advice before stopping 2
- Do not underdose—low doses (2.5-5 mg) provide significantly less benefit than target doses 2, 3, 4