ACE Inhibitors Used in Clinical Practice
Eight ACE inhibitors are recommended for clinical use in heart failure and hypertension, with six having the strongest evidence base for cardiovascular outcomes. 1
Evidence-Based ACE Inhibitors with Proven Mortality Benefit
The following six ACE inhibitors have demonstrated morbidity and mortality reduction in large-scale clinical trials and should be preferentially selected: 1
- Captopril – Initial dose 6.25 mg three times daily, maximum 50 mg three times daily 1
- Enalapril – Initial dose 2.5 mg twice daily, maximum 10–20 mg twice daily 1
- Lisinopril – Initial dose 2.5–5 mg once daily, maximum 20–40 mg once daily 1
- Perindopril – Initial dose 2 mg once daily, maximum 8–16 mg once daily 1
- Ramipril – Initial dose 1.25–2.5 mg once daily, maximum 10 mg once daily 1
- Trandolapril – Initial dose 1 mg once daily, maximum 4 mg once daily 1
Additional ACE Inhibitors with Clinical Use
Two other ACE inhibitors are approved and used in practice, though they lack the extensive outcomes data of the six agents above: 1
- Fosinopril – Initial dose 5–10 mg once daily, maximum 40 mg once daily 1
- Quinapril – Initial dose 5 mg twice daily, maximum 20 mg twice daily 1
Additional ACE Inhibitors Identified in Research
Several other ACE inhibitors have been studied or are available in certain markets, though they are not prominently featured in major U.S. guidelines: 2, 3, 4, 5, 6
- Benazepril 2, 3, 4
- Cilazapril 3, 4
- Delapril 3
- Imidapril 3, 6
- Moexipril 3
- Pentopril 3
- Spirapril 3
- Temocapril 3, 6
- Zofenopril 6
Key Clinical Considerations
All ACE inhibitors share the same mechanism of action—blocking conversion of angiotensin I to angiotensin II—and produce comparable effects on symptoms and survival when dosed appropriately. 1 The available data suggest no clinically meaningful differences among ACE inhibitors in their effects on symptoms or mortality in heart failure. 1
Structural Classification
ACE inhibitors can be grouped by their zinc-binding ligand: 6
- Sulfhydryl-containing (e.g., captopril) 5, 6
- Carboxyl-containing (e.g., enalapril, lisinopril, ramipril, perindopril, trandolapril, quinapril, benazepril, cilazapril) 3, 6
- Phosphinic acid-containing (e.g., fosinopril) 6
Pharmacokinetic Differences
- Captopril has rapid onset and short duration, requiring three-times-daily dosing 4, 5
- Enalapril requires hepatic conversion to the active metabolite enalaprilat, resulting in delayed onset 7, 4, 5
- Lisinopril is active without metabolic conversion but has slow, incomplete absorption 4, 5
- Fosinopril has dual excretion (renal and hepatic), which may be advantageous in renal impairment 8, 3, 6
Common Pitfall
Preference should be given to the six ACE inhibitors with proven mortality benefit (captopril, enalapril, lisinopril, perindopril, ramipril, trandolapril) because these trials clearly defined effective doses for modifying disease progression. 1 This information is generally lacking for ACE inhibitors not tested in large-scale outcomes studies. 1