What is the target dose of lisinopril (Angiotensin-Converting Enzyme inhibitor) in systolic heart failure?

Target Dose of Lisinopril in Systolic Heart Failure

The target dose of lisinopril in systolic heart failure is 30-35 mg once daily, with titration starting from a low dose of 2.5-5.0 mg once daily and increasing gradually to reach the target or maximum tolerated dose. 1

Dosing Strategy

Initial Dosing

• Start with a low dose of 2.5-5.0 mg once daily 2, 1
• For patients with hyponatremia (serum sodium < 130 mEq/L), start with 2.5 mg once daily 3
• For patients with renal impairment (creatinine clearance ≤ 30 mL/min), start with 2.5 mg once daily 3

Titration Process

• Double the dose at intervals of not less than 2 weeks 2, 1
• Continue up-titration until reaching the target dose of 30-35 mg once daily or highest tolerated dose 1
• Monitor blood pressure, renal function, and electrolytes during titration 1

Evidence Supporting Target Dose

The target dose of 30-35 mg is based on clinical guidelines and evidence showing that higher doses of ACE inhibitors provide greater clinical benefits in heart failure:

• The European Society of Cardiology recommends lisinopril target dose of 30-35 mg once daily in systolic heart failure 2, 1
• The ATLAS study demonstrated that high doses of lisinopril (32.5-35 mg daily) were more effective than low doses (2.5-5.0 mg daily) in reducing:
  • Risk of death or hospitalization by 12% (p=0.002) 4
  • Hospitalizations for heart failure by 24% (p=0.002) 4
  • All-cause mortality by 8% (though not statistically significant, p=0.128) 4

Monitoring and Adjustments

Parameters to Monitor

• Blood pressure (watch for symptomatic hypotension)
• Renal function (creatinine, BUN)
• Electrolytes (particularly potassium)
• Body weight and signs of congestion

When to Adjust Dosing

• If symptomatic hypotension occurs: Consider temporary dose reduction
• If creatinine increases >50% from baseline or exceeds 3 mg/dL (266 μmol/L): Consider dose reduction 1
• If hyperkalemia develops (K+ >5.0 mmol/L): Consider dose reduction 2

Special Considerations

• Patients on hemodialysis or with creatinine clearance <10 mL/min should start with 2.5 mg once daily 3
• Asymptomatic low blood pressure usually does not require dose adjustment 2
• Some ACE inhibitor is better than no ACE inhibitor, so maintain the highest tolerated dose even if target cannot be reached 2, 1
• Avoid potassium-sparing diuretics during initiation of therapy 1
• Diuretic dose may need adjustment to minimize hypovolemia that could contribute to hypotension 3

Common Pitfalls to Avoid

1. Underdosing: Many clinicians maintain patients on suboptimal doses. The evidence clearly shows better outcomes with higher doses.
2. Too rapid titration: Always wait at least 2 weeks between dose increases to allow for stabilization.
3. Discontinuing therapy due to mild, asymptomatic hypotension: This rarely requires intervention.
4. Failing to monitor renal function and electrolytes: Regular monitoring is essential, especially during dose adjustments.
5. Stopping therapy due to minor increases in creatinine: Small increases are expected and acceptable.

Remember that the benefits of reaching target doses include improved survival, reduced hospitalizations, and better quality of life for patients with systolic heart failure.