What is the recommended dosage and treatment plan for Lisinopril (angiotensin-converting enzyme inhibitor) in patients with hypertension and heart failure?

Lisinopril Dosage and Treatment Plan for Hypertension and Heart Failure

For patients with both hypertension and heart failure, lisinopril should be initiated at 2.5-5 mg once daily for heart failure (with diuretics) and titrated to a target dose of 20-40 mg daily, with careful monitoring of blood pressure, renal function, and electrolytes. 1, 2

Initial Dosing Strategy

For Heart Failure:

• Starting dose: 5 mg once daily (when used with diuretics and usually digitalis) 1
• Lower starting dose: 2.5 mg once daily for patients with hyponatremia (serum sodium <130 mEq/L) 1
• Titration: Increase gradually to target dose based on tolerance

For Hypertension:

• Starting dose: 10 mg once daily 1
• Starting dose with diuretics: 5 mg once daily 1
• Titration: Adjust according to blood pressure response

Target Dosing

• Heart failure target: Up to 40 mg once daily 1, 2
• Hypertension target: 20-40 mg once daily (doses up to 80 mg have been used but provide limited additional benefit) 1
• Evidence-based target from ATLAS trial: 32.5-35 mg daily (high dose) showed significantly better outcomes than low dose (2.5-5 mg daily) 2, 3

Dose Adjustment for Renal Impairment

• Normal renal function (CrCl >30 mL/min): No dose adjustment required 1
• Moderate impairment (CrCl 10-30 mL/min): Start with half the usual dose (2.5 mg for heart failure) 1, 4
• Severe impairment (CrCl <10 mL/min) or hemodialysis: Initial dose 2.5 mg once daily 1

Titration Protocol

1. Start with low dose (as specified above)
2. Check serum potassium and creatinine after 5-7 days and titrate accordingly 2
3. Recheck every 5-7 days until potassium values are stable 2
4. Double dose at not less than 2-week intervals 2
5. Monitor blood pressure, renal function, and electrolytes 1-2 weeks after each dose increment, at 3 months, and subsequently every 6 months 2

Practical Considerations

When Initiating Therapy:

• Consider reducing or withholding diuretics for 24 hours before starting lisinopril 2
• May be advisable to start treatment in the evening when supine to minimize potential hypotension 2
• When initiated in the morning, supervision for several hours with blood pressure monitoring is advisable in high-risk patients 2

Concomitant Medications:

• Diuretics: May need dose adjustment to minimize hypovolemia 1
• Avoid: NSAIDs, COX-2 inhibitors, and potassium-sparing diuretics during initiation 2, 5

Management of Common Issues

Hypotension:

• If hypotension occurs after initial dose, it does not preclude subsequent careful dose titration 1
• For symptomatic hypotension, consider reducing diuretic dose if no signs of congestion 2

Worsening Renal Function:

• An increase in creatinine up to 50% above baseline or to 3 mg/dL (whichever is greater) is acceptable 2
• If greater rises in creatinine persist despite adjusting concomitant medications, reduce lisinopril dose or discontinue 2

Cough:

• ACE inhibitor-induced cough rarely requires treatment discontinuation 2
• If troublesome cough develops and is proven to be due to ACE inhibition, consider substituting an ARB 2

Clinical Benefits and Evidence

• The ATLAS study demonstrated that high doses of lisinopril (32.5-35 mg daily) were more effective than low doses (2.5-5 mg daily) with: 3

  • 8% lower risk of all-cause mortality
  • 12% lower risk of death or hospitalization
  • 24% fewer hospitalizations for heart failure

• Despite higher incidence of some adverse events with high doses, the frequency of treatment discontinuations was the same in high and low dose groups 6

Common Pitfalls to Avoid

1. Underdosing: Many physicians maintain patients on suboptimal doses. Target doses should be achieved when possible, as higher doses provide greater clinical benefits 2, 3

2. Permanent dose reduction: In clinical trials, 40% of patients who required temporary dose reduction were subsequently restored to target doses, whereas in clinical practice, most dose reductions become permanent 2

3. Excessive fear of adverse effects: The most dramatic decreases in blood pressure occur with the initial dose, while subsequent changes with each dosing increment are comparatively modest 2

4. Failure to manage electrolyte imbalances: Regular monitoring of potassium and renal function is essential, especially when combining with diuretics or other medications 2

5. Abrupt discontinuation of therapy: This should be avoided as it can lead to clinical deterioration 5