Is losartan (angiotensin II receptor antagonist) effective for treating cardiomyopathy?

Losartan for Cardiomyopathy: Efficacy and Clinical Applications

Losartan is beneficial for certain types of cardiomyopathy, particularly in patients with heart failure due to left ventricular systolic dysfunction, but has not shown benefit in hypertrophic cardiomyopathy. 1

Efficacy in Different Types of Cardiomyopathy

Ischemic Cardiomyopathy/Heart Failure with Reduced Ejection Fraction

• Losartan is effective for patients with heart failure due to left ventricular systolic dysfunction (LVEF ≤40%) who are intolerant to ACE inhibitors 2
• Higher doses of losartan (150 mg daily) are more effective than lower doses (50 mg daily):
  • 10% relative risk reduction in death or heart failure hospitalization 3
  • Significant reduction in heart failure hospitalizations (HR 0.87, p=0.025) 3
• Losartan improves heart rate variability and heart rate turbulence in patients with ischemic cardiomyopathy, even when added to beta-blocker and ACE inhibitor therapy 4

Hypertrophic Cardiomyopathy

• The INHERIT trial specifically tested losartan in hypertrophic cardiomyopathy and found no significant difference in left ventricular mass between losartan and placebo after 12 months of treatment 1
• This challenges the view that angiotensin II receptor blockers reduce cardiac hypertrophy in hypertrophic cardiomyopathy 1

Dosing Considerations

• Initial dose: 50 mg once daily for heart failure 5
• Target dose: 150 mg daily for maximum clinical benefit 5, 3
• Titration: Increase no more frequently than every 2 weeks 5
• The HEAAL trial demonstrated that higher doses (150 mg) provide greater clinical benefit than lower doses (50 mg) 2, 3

Clinical Recommendations Based on Guidelines

When to Use Losartan

1. First-line alternative to ACE inhibitors in patients with heart failure and reduced ejection fraction who cannot tolerate ACE inhibitors 2
2. Add-on therapy to standard heart failure treatment in selected cases 2
3. Post-myocardial infarction with left ventricular dysfunction 2

When NOT to Use Losartan

1. Hypertrophic cardiomyopathy - evidence shows no benefit in reducing left ventricular mass 1
2. First-line therapy when ACE inhibitors are tolerated - ACE inhibitors have more robust evidence and are generally preferred 2

Monitoring and Safety Considerations

• Monitor renal function and potassium levels, especially in patients with:
  • Chronic kidney disease
  • Bilateral renal artery stenosis
  • Concomitant potassium-sparing diuretics 5, 6
• Common adverse effects include:
  • Renal impairment
  • Hypotension
  • Hyperkalemia 3
• Better tolerated than ACE inhibitors with lower incidence of cough 2
• Safe to use in patients with left ventricular outflow obstruction 1

Combination Therapy

• Avoid combining losartan with ACE inhibitors in most cases:
  • VALIANT trial showed no additional benefit of combination therapy over monotherapy 2
  • Increased risk of adverse effects with combination therapy 2
• Consider combining with:
  • Beta-blockers
  • Diuretics
  • Mineralocorticoid receptor antagonists (e.g., spironolactone) 5

Clinical Pearls

• Losartan is particularly useful in patients who develop cough with ACE inhibitors
• Higher doses (150 mg) provide greater clinical benefit than lower doses (50 mg)
• No dosage adjustment required in elderly patients or those with mild-to-moderate renal dysfunction 7
• Risk of first-dose hypotension is low compared to ACE inhibitors 7

In summary, losartan is an effective treatment for cardiomyopathy associated with heart failure and reduced ejection fraction, particularly when ACE inhibitors cannot be tolerated, but it has not shown benefit in hypertrophic cardiomyopathy.