What is the recommended dose and frequency of Lisinopril (Angiotensin-Converting Enzyme (ACE) inhibitor) for treating hypertension and heart failure?

Lisinopril Dosing Recommendations for Hypertension and Heart Failure

For hypertension, lisinopril should be started at 10 mg once daily and titrated up to 20-40 mg once daily as a single dose. For heart failure, start at 5 mg once daily (or 2.5 mg if hyponatremic) and titrate up to a target dose of 30-35 mg once daily. 1, 2

Dosing for Hypertension

Initial Dosing

• Standard initial dose: 10 mg once daily 1
• With diuretics: 5 mg once daily 1
• With renal impairment (CrCl ≤30 mL/min): 5 mg once daily 1
• With severe renal impairment (CrCl <10 mL/min): 2.5 mg once daily 1

Maintenance Dosing

• Usual range: 20-40 mg once daily 1
• Maximum dose: Up to 80 mg has been used but with minimal additional benefit 1
• Titration: Adjust according to blood pressure response, typically doubling the dose at 2-week intervals 2

Dosing for Heart Failure

Initial Dosing

• Standard initial dose: 5 mg once daily 1, 2
• With hyponatremia (serum sodium <130 mEq/L): 2.5 mg once daily 1
• With renal impairment (CrCl ≤30 mL/min): 2.5 mg once daily 1

Maintenance Dosing

• Target dose: 30-35 mg once daily 2
• Maximum dose: 40 mg once daily 1
• Titration: Double dose at intervals of not less than 2 weeks 2

Dosing Algorithm

1. Assess baseline renal function and electrolytes

   • If CrCl >30 mL/min: Use standard initial doses
   • If CrCl 10-30 mL/min: Use half of standard initial doses
   • If CrCl <10 mL/min: Start with 2.5 mg once daily

2. Begin treatment

   • For hypertension: Start with 10 mg once daily (or adjusted dose per renal function)
   • For heart failure: Start with 5 mg once daily (or 2.5 mg if hyponatremic)

3. Monitor and titrate

   • Check blood pressure, renal function, and electrolytes 1-2 weeks after each dose increase
   • Double the dose every 2 weeks if tolerated until target dose or blood pressure goal is reached
   • For heart failure, aim for the target dose of 30-35 mg daily or highest tolerated dose

Important Considerations

Evidence for Higher Doses

• The ATLAS study demonstrated that higher doses of lisinopril (32.5-35 mg daily) were more effective than lower doses (2.5-5 mg daily) in reducing hospitalizations for heart failure (24% reduction) and the combined endpoint of death or hospitalization (12% reduction) 3, 4

Monitoring

• Monitor blood chemistry (urea, creatinine, potassium) and blood pressure regularly 2
• An increase in creatinine of up to 50% above baseline is acceptable 2
• Potassium levels up to 6.0 mmol/L may be acceptable 2

Common Pitfalls and Management

1. Hypotension:

   • Asymptomatic low blood pressure usually doesn't require dose adjustment 2
   • For symptomatic hypotension, consider reducing diuretic dose if no signs of congestion 2

2. Cough:

   • ACE inhibitor-induced cough rarely requires discontinuation 2
   • If troublesome, consider switching to an angiotensin receptor blocker 2

3. Worsening renal function:

   • Some increase in BUN, creatinine, and potassium is expected 2
   • If excessive rises occur, consider stopping concomitant nephrotoxic drugs (NSAIDs) 2
   • Consider reducing diuretic dose if no signs of congestion 2

Remember that some ACE inhibitor is better than no ACE inhibitor, so aim for the target dose but settle for the highest tolerated dose if necessary 2.