What are the pros and cons of perindopril (Angiotensin-Converting Enzyme (ACE) inhibitor) vs. lisinopril (ACE inhibitor) in treating hypertension?

Perindopril vs. Lisinopril: Comparative Analysis for Hypertension Management

Perindopril is generally superior to lisinopril for hypertension management due to its better cardiovascular outcomes, particularly in patients with diabetes and stable coronary artery disease, and its more favorable pharmacokinetic profile allowing for better 24-hour blood pressure control.

Pharmacological Differences

Duration of Action and Dosing

• Perindopril:

  • Longer-acting with trough/peak ratios >50%, providing consistent 24-hour blood pressure control 1
  • Once-daily dosing at 4-8mg 2, 3
  • Prodrug converted to active perindoprilat 4

• Lisinopril:

  • Shorter duration of action with less consistent 24-hour coverage
  • Peak effect at 6 hours with diminished effect at 24 hours 5
  • Once-daily dosing at higher doses (20mg+) needed for consistent 24-hour effect 5
  • Not metabolized, excreted unchanged in urine 6

Clinical Efficacy

• Blood Pressure Control:
  • Both effectively lower blood pressure
  • Perindopril shows better arterial compliance and vascular effects 1
  • Lisinopril shows less effectiveness in Black patients compared to non-Black patients 5

Cardiovascular Outcomes

Evidence from Major Trials

• Perindopril:

  • ADVANCE trial demonstrated significant reduction in mortality and major cardiovascular events in patients with diabetes when combined with indapamide 7, 8
  • EUROPA trial showed reduced cardiovascular events in patients with stable coronary artery disease 8, 2
  • Improves arterial compliance and reduces left ventricular mass index 1

• Lisinopril:

  • ALLHAT trial showed no special advantage over chlorthalidone for most cardiovascular outcomes in diabetic patients 7
  • Less effective than chlorthalidone in reducing cardiovascular endpoints in Black patients 7

Special Populations

Diabetes

• Perindopril:

  • Significantly reduced mortality and major cardiovascular events in diabetic patients (ADVANCE trial) 7, 8
  • Lower incidence of hospital admissions due to diabetes compared to lisinopril (7.2% vs 9.6%) 9

• Lisinopril:

  • Higher risk of diabetes-related admissions (adjusted hazard ratio 1.146 to 1.231) 9

Renal Outcomes

• Perindopril:

  • Lower incidence of hospital admissions due to renal diseases (2.3% vs 3.1%) 9
  • Preserves renal function better than lisinopril

• Lisinopril:

  • Higher risk of renal disease admissions (adjusted hazard ratio 1.304 to 1.378) 9
  • Requires significant dose adjustment in renal impairment 6

Coronary Artery Disease

• Perindopril:

  • FDA-approved indication for stable coronary artery disease 2
  • Reduces risk of cardiovascular mortality and non-fatal myocardial infarction 2, 3

• Lisinopril:

  • No specific indication for coronary artery disease in FDA labeling 5

Side Effects and Tolerability

Common Side Effects

• Both share typical ACE inhibitor side effects:
  • Dry cough
  • Hypotension
  • Hyperkalemia
  • Angioedema (higher risk in Black patients) 2

Specific Considerations

• Perindopril:

  • Well-tolerated with similar adverse event profile to other ACE inhibitors 1, 4
  • May require electrolyte monitoring when combined with indapamide 8

• Lisinopril:

  • Can cause significant hyperkalemia in approximately 15% of patients 5
  • More prone to symptomatic hypotension in volume-depleted patients 5

Combination Therapy

With Diuretics

• Perindopril:

  • Particularly effective when combined with indapamide (thiazide-like diuretic) 8
  • Fixed-dose combinations available, improving adherence 8

• Lisinopril:

  • Effective when combined with hydrochlorothiazide 5
  • Combination leads to mean decrease in serum potassium 5

Clinical Decision Algorithm

1. First-line choice:

   • For most patients with hypertension: Perindopril (better 24-hour coverage, vascular effects)
   • For patients with stable coronary artery disease: Perindopril (specific indication)
   • For patients with diabetes: Perindopril (better outcomes in ADVANCE trial)

2. Consider lisinopril when:

   • Cost is the primary concern (generic lisinopril may be less expensive)
   • Patient has previously tolerated lisinopril well
   • Simplified renal dosing is needed (excreted unchanged)

3. Dosing considerations:

   • Start perindopril at 4mg daily, titrate to 8mg if needed
   • Start lisinopril at 10mg daily, may require 20mg+ for consistent 24-hour control

4. Monitoring:

   • Both require monitoring of renal function and potassium levels
   • More vigilant monitoring needed with lisinopril in renal impairment

Key Takeaways

1. Perindopril offers better 24-hour blood pressure control with once-daily dosing
2. Perindopril has stronger evidence for cardiovascular protection, especially in diabetes and coronary artery disease
3. Perindopril shows better outcomes for renal protection compared to lisinopril
4. Both medications share similar side effect profiles typical of ACE inhibitors
5. Perindopril works particularly well in combination with indapamide