What is the recommended frequency for increasing the dose of lisinopril (angiotensin-converting enzyme inhibitor) in a patient with uncontrolled hypertension or heart failure?

Lisinopril Dose Titration Frequency

Increase lisinopril every 2 weeks when titrating to target dose, monitoring blood pressure, renal function, and potassium 1-2 weeks after each dose increment. 1, 2, 3

Titration Protocol

Standard Titration Interval

• Titrate at intervals of not less than 2 weeks based on blood pressure response and tolerability 1, 2, 3, 4
• Some patients may require slower titration, but 2 weeks is the minimum recommended interval 5

Target Doses by Indication

For Heart Failure:

• Start at 2.5-5 mg once daily 5, 2, 4
• Target dose is 30-35 mg once daily (not the commonly used lower doses) 1, 2, 3
• The ATLAS trial definitively showed that high-dose lisinopril (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) 2, 3, 6
• Aim for at least 50% of target dose (minimum 15-17.5 mg daily) if full target cannot be achieved 3

For Hypertension:

• Start at 10 mg once daily 1
• Target dose is 20-40 mg once daily 1, 4

Post-Myocardial Infarction:

• Day 1: 5 mg, Day 2: 5 mg, Day 3: 10 mg, then 10 mg daily ongoing 2, 4

Mandatory Monitoring Schedule

Check the following at each titration:

• Blood pressure, serum creatinine, and potassium at baseline 5, 2
• Recheck 5-7 days after starting therapy 5, 2
• Monitor 1-2 weeks after each dose increment 5, 1, 2
• Recheck every 5-7 days during titration until potassium stabilizes 5, 2
• Once stable: check at 3 months, then every 6 months 5, 1, 2

Acceptable Changes During Titration

Creatinine elevation:

• Up to 50% increase above baseline OR up to 3 mg/dL (whichever is greater) is acceptable 1, 2, 3
• If creatinine rises beyond this threshold, stop titration and consider dose reduction 5

Hypotension management:

• Asymptomatic hypotension does not require dose reduction 3
• If symptomatic hypotension occurs, reduce diuretic dose first before lowering lisinopril 3
• Initial hypotension does not preclude continued careful titration 4

Critical Pitfalls to Avoid

Undertitration is the most common error:

• Many clinicians stop at 5-10 mg daily for heart failure, missing the proven mortality benefit of higher doses 2
• The evidence clearly demonstrates that 30-35 mg daily is superior to 2.5-5 mg daily 2, 3, 6

Medication interactions:

• Avoid NSAIDs and COX-2 inhibitors—they reduce ACE inhibitor efficacy and worsen renal function 2
• Avoid potassium-sparing diuretics during initiation unless needed for persistent hypokalemia 5, 2

Premature discontinuation:

• Despite higher adverse event rates with high-dose lisinopril, discontinuation rates were identical to low-dose groups in ATLAS 6
• Most adverse effects (hypotension, worsening renal function) can be managed by adjusting concomitant medications rather than stopping lisinopril 6

Renal Impairment Adjustments

• No adjustment needed if creatinine clearance >30 mL/min 4
• If CrCl 10-30 mL/min: start at half the usual dose (2.5 mg for heart failure, 5 mg for hypertension) 4
• If CrCl <10 mL/min or on hemodialysis: start at 2.5 mg once daily 4