What are the most effective Angiotensin-Converting Enzyme (ACE) inhibitors and Angiotensin Receptor Blockers (ARBs) in terms of efficacy and side effect profile?

ACE Inhibitors vs ARBs: Efficacy and Side Effect Profile Comparison

ACE inhibitors and ARBs are both effective for cardiovascular conditions, but ARBs have a superior side effect profile with similar efficacy, making them preferable when tolerability is a concern. 1

Efficacy Comparison

ACE Inhibitors

• All available ACE inhibitors have similar effects on symptoms and survival in heart failure with reduced ejection fraction (HFrEF) 1
• ACE inhibitors are considered first-line therapy for:
  • Heart failure with reduced ejection fraction 1
  • Post-myocardial infarction patients 1
  • Patients with diabetic nephropathy 1
• Most effective agents based on evidence:
  • Enalapril: Extensively studied in heart failure trials and considered a benchmark agent 1, 2
  • Captopril: Well-established efficacy in post-MI settings 1, 3
  • Lisinopril: Commonly used due to once-daily dosing advantage 1

ARBs

• ARBs produce similar hemodynamic, neurohormonal, and clinical effects to ACE inhibitors 1
• ARBs are recommended as alternatives when ACE inhibitors are not tolerated 1
• Most effective agents based on evidence:
  • Valsartan: Proven efficacy in heart failure and post-MI settings 1, 3
  • Candesartan: Demonstrated benefits in heart failure, including those with preserved ejection fraction 1
  • Losartan: Well-studied in hypertension 1

Side Effect Profile Comparison

ACE Inhibitors

• Common side effects include:
  • Cough (occurs in up to 20% of patients) due to kininase inhibition 1, 4
  • Angioedema (occurs in <1% of patients, more frequent in blacks and women) 1
  • Hypotension, especially in patients with volume depletion 1, 2
  • Hyperkalemia 2, 4
  • Renal dysfunction, particularly in patients with pre-existing renal insufficiency 1, 2

ARBs

• ARBs have a more favorable side effect profile compared to ACE inhibitors 3, 5, 6
• Side effects include:
  • Significantly lower incidence of cough compared to ACE inhibitors 1, 3, 6
  • Much lower risk of angioedema 1, 6
  • Similar risks of hypotension, renal dysfunction, and hyperkalemia as ACE inhibitors 3, 6
  • Overall discontinuation rates similar to placebo 6

Clinical Decision Algorithm

1. For initial therapy in most cardiovascular conditions:

   • Start with an ACE inhibitor (preferably enalapril, lisinopril, or ramipril) due to more robust mortality data 1, 7
   • Begin at low doses and titrate upward to target doses shown effective in clinical trials 1

2. Switch to ARB if patient develops:

   • Persistent dry cough (most common reason for switching) 1, 4, 6
   • Angioedema (absolute indication to switch) 1, 6
   • Other intolerable side effects despite dose adjustment 1

3. Consider ARB as initial therapy when:

   • Patient has history of ACE inhibitor-induced cough or angioedema 1, 6
   • Patient is at higher risk for ACE inhibitor side effects (e.g., black patients have higher angioedema risk) 1

4. For specific conditions:

   • Heart failure: Consider ARNI (sacubitril/valsartan) over both ACE inhibitors and ARBs 1
   • Hypertension in black patients: ARBs may be better tolerated than ACE inhibitors 1
   • Diabetic nephropathy: Both ACE inhibitors and ARBs are effective 1

Important Clinical Pearls

• ARBs should not be initiated within 36 hours of discontinuing an ACE inhibitor due to risk of overlapping effects 1
• Combination therapy with both ACE inhibitor and ARB is generally not recommended due to increased adverse effects without significant additional benefit 1, 8
• Monitor renal function, potassium, and blood pressure closely when initiating either class of medication 1, 3
• Both drug classes should be used with caution in patients with renal insufficiency, elevated serum potassium, or low systemic blood pressure 1
• The incidence of cough with ACE inhibitors may be overestimated in clinical practice 4
• ARBs have similar efficacy to ACE inhibitors but with better tolerability, making them an excellent alternative when ACE inhibitors cannot be used 5, 6