What is the difference in duration of action between losartan (Angiotensin II Receptor Antagonist) and enalapril (Angiotensin-Converting Enzyme Inhibitor)?

Losartan vs Enalapril: Duration of Action Comparison

Losartan has a shorter duration of action compared to enalapril, with losartan requiring once or twice daily dosing due to its 6-9 hour half-life (for its active metabolite), while enalapril provides more consistent 24-hour coverage with once or twice daily dosing.

Pharmacokinetic Differences

Losartan

• Half-life:
  • Parent compound: 1-2 hours
  • Active metabolite (E-3174): 6-9 hours 1
• Dosing frequency:
  • Typically once daily, but may require twice daily dosing in some patients 2
  • Initial dose: 25-50 mg once daily
  • Maximum dose: 50-100 mg daily 3, 2
• Duration of action:
  • Shorter than enalapril due to the half-life of its active metabolite
  • May not provide full 24-hour coverage at lower doses 1

Enalapril

• Half-life:
  • Longer effective duration due to its active metabolite enalaprilat
  • Provides more consistent 24-hour coverage
• Dosing frequency:
  • Initial dose: 2.5 mg twice daily
  • Maximum dose: 10-20 mg twice daily 3
• Duration of action:
  • More consistent 24-hour coverage, especially when dosed twice daily

Clinical Implications of Duration Differences

Blood Pressure Control

• Morning surge coverage:
  • Enalapril may provide better coverage of early morning blood pressure surge due to its longer duration of action
  • Losartan at lower doses may not provide complete 24-hour coverage, potentially requiring twice-daily dosing 2, 1

Medication Adherence

• Single daily dosing improves adherence
• Both medications can be dosed once daily, but:
  • Losartan may require twice-daily dosing for optimal 24-hour coverage in some patients
  • Enalapril is often prescribed twice daily for optimal effect 3

Efficacy Considerations

Left Ventricular Hypertrophy Regression

• Losartan demonstrated superior left ventricular mass reduction (21.7 g/m²) compared to atenolol (17.7 g/m²) in the LIFE trial 3
• ACE inhibitors like enalapril were shown to be the most effective agents for LVH regression in a meta-analysis, leading to a 13.3% reduction in left ventricular mass compared to 9.3% for calcium channel blockers 3

Proteinuria Reduction

• Both medications are effective in reducing proteinuria
• In children with Alport syndrome, losartan maintained proteinuria reduction while enalapril produced further proteinuria reduction over a 3-year period 4

Side Effect Profile Differences

Cough

• ACE inhibitors like enalapril commonly cause dry cough (up to 20% of patients)
• Losartan and other ARBs rarely cause cough, making them suitable alternatives for patients who develop cough on ACE inhibitors 3

Angioedema

• Both can cause angioedema, but it's more common with ACE inhibitors like enalapril
• ARBs like losartan may still cause angioedema in patients who previously experienced it with ACE inhibitors 3

Practical Prescribing Considerations

When to Choose Losartan

• Patients who experienced ACE inhibitor-induced cough
• Patients requiring once-daily dosing who tolerate ARBs well
• Patients with left ventricular hypertrophy (based on LIFE trial data) 3

When to Choose Enalapril

• Patients requiring more consistent 24-hour blood pressure control
• Patients who have tolerated ACE inhibitors well in the past
• Patients with heart failure (extensive evidence base)

Important Monitoring Considerations

• For both medications:
  • Monitor renal function before and periodically during treatment
  • Monitor blood pressure within 1-2 weeks after initiation or dose changes
  • Both are contraindicated in pregnancy 2

When switching between these medications, consider the differences in duration of action and adjust dosing frequency accordingly to maintain consistent blood pressure control throughout the 24-hour period.