What is the appropriate dosing of lisinopril for a patient with hypertension or heart failure, considering factors such as renal impairment, elderly age, and concomitant medications?

Lisinopril Dosing

Hypertension

For hypertension, start lisinopril at 10 mg once daily and titrate up to 40 mg once daily based on blood pressure response. 1

• Initial dose: 10 mg once daily is the standard starting dose for most patients with hypertension 1
• Dose adjustment: Titrate upward based on blood pressure response, with a maximum dose of 40 mg once daily 1
• Combination therapy: If blood pressure remains uncontrolled on lisinopril alone, add a low-dose diuretic (e.g., hydrochlorothiazide 12.5 mg), which may then allow reduction of the lisinopril dose 1
• Patients already on diuretics: Start at 5 mg once daily to minimize risk of symptomatic hypotension 1

Heart Failure

For heart failure with reduced ejection fraction, start at 5 mg once daily (or 2.5 mg if hyponatremic) and titrate to a target dose of 20-40 mg once daily, aiming for at least 10 mg daily for optimal mortality benefit. 2, 1

Starting Doses

• Standard starting dose: 5 mg once daily when used with diuretics and digitalis 1
• Hyponatremia (sodium <130 mEq/L): Start at 2.5 mg once daily 1
• Target dose: The American College of Cardiology recommends 20-40 mg once daily, with higher doses demonstrating superior mortality reduction 2
• Minimum effective dose: At least 50% of target dose (10 mg daily) should be achieved for optimal clinical benefit 2

Titration Strategy

• Increase doses at intervals of not less than 2 weeks 2
• Aim for the highest tolerated dose, as mortality benefit is dose-dependent; high-dose lisinopril (32.5-35 mg daily) reduced death or hospitalization by 12% and heart failure hospitalizations by 24% compared to lower doses 2
• Maximum dose: 40 mg once daily 1

Monitoring During Titration

• Check blood pressure, serum creatinine, and potassium within 5-7 days after initiation or dose increases 2
• Continue monitoring at 3 months, then every 6 months during maintenance therapy 2
• Acceptable creatinine increase: Up to 50% above baseline is acceptable when initiating or uptitrating therapy 2
• Asymptomatic hypotension does not require dose reduction; if symptomatic hypotension occurs, consider reducing diuretic dose before lowering lisinopril 2

Acute Myocardial Infarction

For hemodynamically stable patients within 24 hours of acute MI, give 5 mg orally 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 blood pressure (≤120 mmHg and >100 mmHg): Start at 2.5 mg during the first 3 days 1
• Hypotension (systolic BP ≤100 mmHg): Use a maintenance dose of 5 mg daily with temporary reductions to 2.5 mg if needed 1
• Prolonged hypotension (systolic BP <90 mmHg for >1 hour): Withdraw lisinopril 1

Renal Impairment Adjustments

Dose adjustments are required for creatinine clearance ≤30 mL/min to prevent drug accumulation. 1

• CrCl >30 mL/min: No dose adjustment required 1
• CrCl 10-30 mL/min: Reduce initial dose to half the usual recommended dose:
  • Hypertension: 5 mg initially 1
  • Heart failure: 2.5 mg initially 1
  • Acute MI: 2.5 mg initially 1
  • Titrate as tolerated to maximum of 40 mg daily 1
• Hemodialysis or CrCl <10 mL/min: Start at 2.5 mg once daily 1
• Renal function monitoring: Studies in patients with impaired renal function (GFR ≤60 mL/min) showed that lisinopril effectively controlled blood pressure with median doses of 10 mg daily without worsening renal function 3, 4

Pediatric Dosing (Age ≥6 years)

For children with GFR >30 mL/min/1.73m², start at 0.07 mg/kg once daily (up to 5 mg total) and titrate to maximum of 0.61 mg/kg (up to 40 mg) once daily. 1

• Not recommended: In children <6 years or with GFR <30 mL/min/1.73m² 1

Elderly Patients

Elderly patients respond well to lisinopril at the same dosage ranges as younger adults (2.5-40 mg/day), though lower starting doses may be prudent given higher rates of renal impairment. 5

• Dosages of 2.5-40 mg/day are effective in elderly patients, with 68-89% achieving blood pressure control 5
• Age-related differences in antihypertensive efficacy are not clinically significant 5
• Consider lower starting doses if significant renal impairment is present 5

Common Pitfalls and Monitoring

Adverse Effects to Monitor

• Symptomatic hypotension: Most common with initial doses, particularly in volume-depleted patients or those on diuretics 2
• Hyperkalemia: Monitor potassium levels, especially when combined with potassium-sparing diuretics or supplements 2
• ACE inhibitor cough: Occurs in up to 20% of patients but rarely requires discontinuation 2
• Angioedema: A potentially life-threatening reaction warranting permanent discontinuation of all ACE inhibitors 2

Key Monitoring Parameters

• Blood pressure and clinical symptoms during initiation and dose adjustments 2
• Serum creatinine, urea, and potassium within 5-7 days of initiation or dose changes 2
• Diuretic dose may need adjustment to minimize hypovolemia and hypotension 1