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

For heart failure with reduced ejection fraction, start lisinopril at 2.5-5 mg once daily and titrate to a target dose of 20-40 mg once daily, with higher doses (32.5-35 mg daily) demonstrating superior mortality reduction compared to lower doses (2.5-5 mg daily). 1, 2

Heart Failure Dosing

Target the highest tolerated dose, as mortality benefit is dose-dependent:

• Starting dose: 5 mg once daily in stable patients; reduce to 2.5 mg once daily if hyponatremia (serum sodium <130 mEq/L) is present 3
• Target dose: 20-40 mg once daily, with the ATLAS trial demonstrating that high-dose lisinopril (32.5-35 mg daily) reduced mortality significantly more than low-dose (2.5-5 mg daily) 1, 2
• Minimum effective dose: Achieve at least 50% of target dose (≥10 mg daily) for optimal clinical benefit 2
• Titration schedule: Increase dose at intervals of not less than 2 weeks, monitoring blood pressure, renal function, and potassium at each adjustment 2

The European Society of Cardiology emphasizes that 30-35 mg once daily provides a 12% lower risk of death or hospitalization and 24% fewer heart failure hospitalizations compared to lower doses. 2

Hypertension Dosing

• Starting dose: 10 mg once daily in most patients 3, 4
• With concurrent diuretic use: Start at 5 mg once daily 3
• Dose range: 10-40 mg once daily, with most patients responding to 20-40 mg daily 3, 5, 4
• Pediatric patients (≥6 years): Start at 0.07 mg/kg once daily (maximum 5 mg), titrate to maximum 0.61 mg/kg (up to 40 mg) once daily 3

Acute Myocardial Infarction Dosing

Initiate within 24 hours of symptom onset in hemodynamically stable patients:

• Standard regimen: 5 mg on day 1,5 mg at 24 hours, 10 mg at 48 hours, then 10 mg once daily for at least 6 weeks 3
• Low systolic BP (100-120 mmHg): Start at 2.5 mg 3
• Hypotension management: If systolic BP ≤100 mmHg, maintain at 5 mg daily with temporary reductions to 2.5 mg as needed; discontinue if systolic BP <90 mmHg for >1 hour 3

Renal Impairment Adjustments

Dose reduction is mandatory in moderate to severe renal dysfunction:

• CrCl >30 mL/min: No adjustment needed 3
• CrCl 10-30 mL/min: Reduce initial dose by 50% (hypertension: 5 mg; heart failure: 2.5 mg; post-MI: 2.5 mg), titrate to maximum 40 mg daily 3, 6
• CrCl <10 mL/min or hemodialysis: Start at 2.5 mg once daily 3

Studies demonstrate that lisinopril maintains efficacy in renal impairment without worsening GFR when dosed appropriately, with median effective doses of 10 mg daily in patients with baseline GFR as low as 10-60 mL/min. 6, 7

Monitoring Requirements

Close surveillance during initiation and titration is essential:

• Blood chemistry: Monitor urea, creatinine, and potassium before initiation and after each dose adjustment 2
• Acceptable creatinine increase: Up to 50% above baseline is acceptable during initiation or uptitration 2
• Hypotension management: Asymptomatic hypotension does not require dose reduction; if symptomatic, reduce diuretic dose before lowering lisinopril 2
• Potassium monitoring: Particularly important when combined with potassium-sparing diuretics, aldosterone antagonists, or supplements 2

Elderly Patients

• Dosing: Same as general population (2.5-40 mg daily), though lower doses may be needed due to age-related renal decline 8, 4
• Efficacy: 68-89% of elderly patients achieve blood pressure control with lisinopril 8
• Post-MI benefit: Elderly patients show similar mortality reduction to younger patients, with a notable 25.5% reduction in risk of low ejection fraction 8

Critical Safety Considerations

Angioedema is a life-threatening reaction requiring permanent discontinuation of all ACE inhibitors. 2

• First-dose hypotension: Most common in volume-depleted patients or those on diuretics; ensure adequate hydration before initiation 3
• Cough: Occurs in up to 20% of patients but rarely requires discontinuation 2
• Combination therapy caution: Avoid combining with ARBs in acute settings (post-MI) due to increased adverse effects without added benefit, though combination may be beneficial in stable chronic heart failure 1

Concomitant Diuretic Use

When adding lisinopril to existing diuretic therapy, temporary diuretic dose reduction may prevent excessive hypotension:

• Diuretic dose may need adjustment to minimize hypovolemia and hypotension 3
• The appearance of hypotension after initial dosing does not preclude careful subsequent titration 3
• Lisinopril attenuates thiazide-induced hypokalemia 5