Low Dose ACE Inhibitor Recommendations
Low dose ACE inhibitor therapy should be initiated at specific doses based on the medication selected, with captopril starting at 6.25 mg three times daily, enalapril at 2.5 mg twice daily, and lisinopril at 2.5-5 mg once daily. 1, 2
Recommended Initial Low Doses by Medication
- For lisinopril, the recommended low dose for heart failure is 5 mg once daily, with an even lower dose of 2.5 mg once daily for patients with hyponatremia (serum sodium <130 mEq/L) 2
- For patients with hypertension taking diuretics, the recommended starting dose of lisinopril is 5 mg once daily 2
- For heart failure patients, captopril should be initiated at 6.25 mg three times daily, enalapril at 2.5 mg twice daily, and ramipril at 1.25-2.5 mg once daily 1
- For post-myocardial infarction patients with low systolic blood pressure (≤120 mmHg and >100 mmHg), lisinopril should be initiated at 2.5 mg 2
Titration and Target Doses
- Treatment with an ACE inhibitor should be initiated at low doses, followed by gradual increments if lower doses have been well tolerated 3
- Clinicians should attempt to use doses that have been shown to reduce the risk of cardiovascular events in clinical trials, with target doses for lisinopril being 20-40 mg daily for hypertension and up to 40 mg daily for heart failure 3, 2
- The American College of Cardiology considers 50% of the target dose to be the minimum effective dose for clinical benefit 3, 4
- Higher doses of ACE inhibitors were better than low doses in reducing the risk of hospitalization, but showed similar effects on symptoms and mortality 3, 5
Monitoring and Safety Considerations
- Renal function and serum potassium should be assessed within 1-2 weeks of initiation of therapy and periodically thereafter, especially in patients with preexisting hypotension, hyponatremia, diabetes mellitus, or azotemia 3
- For patients with creatinine clearance ≥10 mL/min and ≤30 mL/min, reduce the initial dose of lisinopril to half of the usual recommended dose 2
- For patients on hemodialysis or with creatinine clearance <10 mL/min, the recommended initial dose of lisinopril is 2.5 mg once daily 2
- In the ATLAS study, more than 90% of patients were successfully titrated to their assigned target doses, demonstrating that most patients with heart failure can tolerate ACE inhibitor therapy 6, 5
Special Populations
- For elderly patients or those with low blood pressure, starting with lower doses and potentially using split dosing may improve tolerability 4
- In patients with heart failure, ensure appropriate diuretic dosing before and during ACE inhibitor treatment, as fluid retention can blunt therapeutic effects and fluid depletion can potentiate adverse effects 3
- For patients who cannot tolerate once-daily target doses, splitting into twice-daily administration of lower doses is a reasonable approach to achieve the total daily target dose 4
Common Pitfalls and Caveats
- ACE inhibitors are commonly prescribed in clinical practice at much lower doses than those shown to reduce morbidity and mortality in clinical trials 3, 7
- Abrupt withdrawal of ACE inhibitor treatment can lead to clinical deterioration and should be avoided in the absence of life-threatening complications 3, 1
- Nonsteroidal anti-inflammatory drugs can block the favorable effects and enhance the adverse effects of ACE inhibitors and should be avoided 3
- For patients with heart failure, clinicians should not delay the institution of beta-blockers because of a failure to reach target ACE inhibitor doses 3