What is the best Angiotensin-Converting Enzyme (ACE) inhibitor?

Selecting the Best ACE Inhibitor

There is no single "best" ACE inhibitor for all patients, as the choice should be based on specific comorbidities, with lisinopril, ramipril, and enalapril being the most evidence-supported options for cardiovascular outcomes. 1, 2

First-Line ACE Inhibitors Based on Guidelines

ACE inhibitors are among the first-line agents for hypertension along with thiazide diuretics, calcium channel blockers (CCBs), and angiotensin receptor blockers (ARBs) according to the 2017 ACC/AHA guidelines 1. When selecting an ACE inhibitor, consider:

• Evidence base: Lisinopril, ramipril, and enalapril have the most robust clinical trial data
• Dosing convenience: Once-daily options (lisinopril, ramipril, perindopril, fosinopril, trandolapril) improve adherence
• Pharmacokinetics: Trandolapril, ramipril, and fosinopril have trough-to-peak ratios >50%, providing better 24-hour coverage 3

ACE Inhibitor Selection Algorithm

1. For heart failure patients:

   • Captopril, enalapril, lisinopril, ramipril, fosinopril, perindopril, quinapril, or trandolapril (all have shown mortality benefit) 1, 2
   • Dosing ranges from initial low doses to target doses shown in clinical trials 2

2. For post-myocardial infarction:

   • Ramipril (reduced mortality by 27% in post-MI patients) 2
   • Lisinopril (GISSI-3 trial showed reduced mortality) 4
   • Trandolapril (18-27% all-cause mortality reduction) 3

3. For diabetic nephropathy:

   • Lisinopril (shown to prevent development of nephropathy) 4, 3
   • Captopril (delays progression of diabetic nephropathy) 3

4. For Black patients:

   • Consider thiazide diuretics or CCBs as first-line instead, as ACE inhibitors are less effective in this population 1
   • If ACE inhibitor needed, ARBs may be better tolerated (less cough and angioedema) 1

Specific ACE Inhibitor Characteristics

ACE Inhibitor	Key Advantages	Initial Dose	Maximum Dose
Lisinopril	Linear dose-response curve, no hepatic activation needed, once-daily dosing	2.5-5 mg once daily	20-40 mg once daily
Ramipril	Good trough-to-peak ratio, strong post-MI data	1.25-2.5 mg once daily	10 mg once daily
Enalapril	Extensive clinical trial data	2.5 mg twice daily	10-20 mg twice daily
Trandolapril	Excellent trough-to-peak ratio, post-MI benefits	1 mg once daily	4 mg once daily
Fosinopril	Good trough-to-peak ratio, dual elimination (renal/hepatic)	5-10 mg once daily	40 mg once daily

Important Considerations and Caveats

• Adverse effects: Monitor for cough (up to 20% of patients), angioedema (<1%, more common in Black patients), hyperkalemia, and renal dysfunction 2, 5
• Underdosing: Many clinicians underdose ACE inhibitors; aim for target doses shown in clinical trials 2
• Renal function: Dose adjustment needed for most ACE inhibitors in renal impairment, except fosinopril (dual elimination pathway) 3, 6
• Bioavailability: Lisinopril is the only ACE inhibitor that doesn't require hepatic activation, though its bioavailability is only about 25% 6

ACE inhibitors as a class have similar efficacy when used at appropriate doses. The choice between them should be guided by specific patient factors including comorbidities, dosing convenience, and side effect profile rather than assuming one is universally superior to others.