What is the comparative strength of Trandalopril (trandolapril) vs Lisinopril as angiotensin-converting enzyme (ACE) inhibitors?

Comparative Strength of Trandolapril vs Lisinopril as ACE Inhibitors

Trandolapril is more potent than lisinopril on a milligram-per-milligram basis, with 4 mg of trandolapril being equivalent to approximately 20-35 mg of lisinopril for clinical outcomes in cardiovascular disease. 1

Pharmacological Comparison

Potency and Dosing

• Trandolapril has higher potency with a target dose of 4 mg daily compared to lisinopril's target dose of 30-35 mg daily 1
• The dosing ratio suggests trandolapril is approximately 7-8 times more potent per milligram than lisinopril
• Starting doses reflect this potency difference: trandolapril 1 mg vs. lisinopril 2.5-5 mg 1

Pharmacokinetic Properties

• Trandolapril:

  • Prodrug converted to active metabolite trandolaprilat 2
  • Lower bioavailability (11%) compared to lisinopril 3
  • Longer half-life (approximately 75 hours for trandolaprilat) 4
  • Higher lipophilicity, allowing better tissue penetration 5
  • Dual elimination pathway (renal and hepatic) 3

• Lisinopril:

  • Not a prodrug; active in its administered form 6
  • Higher bioavailability (approximately 25%) 6
  • Shorter half-life compared to trandolaprilat 6
  • Exclusively eliminated through kidneys 6, 3

Clinical Efficacy

Blood Pressure Control

• Trandolapril provides effective 24-hour blood pressure control with a trough/peak ratio consistently ≥50% 2, 5
• Lisinopril's antihypertensive effect begins within 2 hours, peaks around 6 hours, and lasts for 24 hours 6
• Both are effective once-daily agents for hypertension management 1

Cardiovascular Outcomes

• Trandolapril demonstrated a 7% absolute reduction in mortality in the TRACE trial for patients with left ventricular dysfunction after myocardial infarction 1, 2
• Lisinopril showed dose-dependent mortality benefits in heart failure in the ATLAS trial, with high doses (32.5-35 mg) being superior to low doses (2.5-5 mg) 1
• In the ALLHAT study, lisinopril was associated with higher rates of stroke (RR 1.15) and combined cardiovascular disease (RR 1.10) compared to chlorthalidone 1

Clinical Considerations

Patient-Specific Factors

• Renal impairment:

  • Trandolapril may be preferred in patients with renal dysfunction due to its dual elimination pathway 3
  • Lisinopril requires significant dose adjustment in renal impairment (creatinine clearance ≤30 ml/min) 3

• Hepatic impairment:

  • Lisinopril may be preferred in patients with liver disease due to its renal elimination 3

Common Side Effects

• Both medications share similar side effect profiles typical of ACE inhibitors:
  • Cough (most common)
  • Dizziness
  • Hypotension
  • Hyperkalemia
  • Renal dysfunction 1

Practical Prescribing Guidelines

Dose Equivalence

When switching between these medications, consider the following approximate equivalence:

• Trandolapril 1 mg ≈ Lisinopril 7-8 mg
• Trandolapril 2 mg ≈ Lisinopril 15-16 mg
• Trandolapril 4 mg ≈ Lisinopril 30-35 mg

Monitoring

• For both medications:
  • Check renal function and electrolytes 1-2 weeks after initiation and after each dose increase 7
  • Monitor blood pressure regularly
  • Assess for common side effects, particularly cough and dizziness

Conclusion

While both trandolapril and lisinopril are effective ACE inhibitors, trandolapril offers higher potency on a milligram-per-milligram basis, longer duration of action, and potential advantages in patients with renal impairment due to its dual elimination pathway. The choice between these agents should consider the patient's renal function, comorbidities, and dosing convenience.