What is the maximum recommended dose of Lisinopril (Angiotensin-Converting Enzyme (ACE) inhibitor) for a patient with hypertension or heart failure, considering factors such as renal function and potassium levels?

Maximum Dose of Lisinopril

The maximum recommended dose of lisinopril is 40 mg once daily for both hypertension and heart failure, with dose adjustments required for renal impairment. 1, 2

Maximum Dosing by Indication

Hypertension

• Maximum dose: 40 mg once daily 1, 2
• Starting dose: 10 mg once daily (or 5 mg if on diuretics) 2
• Pediatric patients (≥6 years): Maximum 0.61 mg/kg once daily (not to exceed 40 mg) 2

Heart Failure with Reduced Ejection Fraction (HFrEF)

• Maximum dose: 40 mg once daily 1, 2
• Target dose: 20-40 mg once daily for optimal mortality benefit 1
• The 2017 ACC/AHA guidelines specify that clinical trials achieved mean doses of 32.5-35 mg daily 1
• Starting dose: 5 mg once daily (2.5 mg if hyponatremic with sodium <130 mEq/L) 2
• The ATLAS trial demonstrated that higher 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

Acute Myocardial Infarction

• Maximum dose: 10 mg once daily (lower than other indications) 2
• Initiate with 5 mg within 24 hours, then 5 mg at 24 hours, 10 mg at 48 hours, then 10 mg daily 2
• Use 2.5 mg starting dose if systolic BP 100-120 mmHg 2

Dose Adjustments for Renal Impairment

Renal function is the primary factor requiring dose modification: 2

• CrCl >30 mL/min: No adjustment needed; full 40 mg maximum dose allowed 2
• CrCl 10-30 mL/min: Start at half the usual dose (5 mg for hypertension, 2.5 mg for heart failure); maximum still 40 mg daily with careful titration 2
• CrCl <10 mL/min or hemodialysis: Start at 2.5 mg once daily; titrate cautiously to maximum 40 mg 2
• Lisinopril accumulates in severe renal failure, though this does not cause excessive antihypertensive effects 4

Titration Protocol

Follow this stepwise approach to reach maximum dose: 1

1. Start with low dose (see above by indication) 1
2. Double the dose at minimum 2-week intervals 1
3. Monitor blood pressure, serum creatinine, and potassium within 1-2 weeks of each dose change 1
4. Continue titration until target/maximum dose reached or limiting adverse effects occur 1

Monitoring Requirements at Maximum Dose

Essential parameters to monitor: 1

• Creatinine increase up to 50% above baseline is acceptable and does not require dose reduction 1
• Potassium >5.5 mmol/L: Requires intervention; avoid potassium supplements and potassium-sparing diuretics 1
• Symptomatic hypotension: Consider reducing diuretic dose before lowering lisinopril 1
• Asymptomatic hypotension does not require dose adjustment 1

Important Caveats

Contraindications to maximum dosing: 1

• Systolic BP <80 mmHg or symptomatic hypotension 1
• Serum creatinine >3 mg/dL (>221 μmol/L) requires specialist consultation 1
• Bilateral renal artery stenosis 1
• Baseline potassium >5.5 mmol/L 1
• Pregnancy (all ACE inhibitors are contraindicated) 1
• History of angioedema with ACE inhibitors 1

Clinical pearls: 1, 3

• Some ACE inhibitor is better than no ACE inhibitor—use the highest tolerated dose even if target cannot be reached 1
• In heart failure, aim for at least 50% of target dose (≥10 mg daily) for clinical benefit 5
• Higher doses provide superior outcomes in heart failure but require careful monitoring for hypotension and renal function 3
• Cough occurs in up to 20% of patients but rarely requires discontinuation 5