Is eplontersen effective for treating heart failure?

Eplontersen for Heart Failure: Current Evidence and Recommendations

Based on the available evidence, eplontersen is not currently recommended for the treatment of heart failure as there is insufficient data supporting its use for this indication.

Current Evidence for Eplontersen in Heart Failure

The only study examining eplontersen in a cardiac context is a 2024 research study that evaluated its effects specifically in patients with hereditary transthyretin amyloidosis (ATTRv) with polyneuropathy and cardiomyopathy 1. This study found:

• Improvement in left ventricular ejection fraction of 4.3% compared to placebo
• Improvement in stroke volume of 10.64 mL compared to placebo
• Stable measures of cardiac structure and function

However, this evidence is:

• Limited to a specific type of cardiomyopathy (transthyretin amyloidosis)
• Not focused on general heart failure populations
• From a single study with notable baseline differences between treatment and control groups
• Currently being further investigated in the ongoing CARDIO-TTRansform trial

Established Heart Failure Treatments

Current guidelines recommend the following evidence-based therapies for heart failure:

First-Line Therapies

• ACE inhibitors and beta-blockers form the cornerstone of heart failure treatment with reduced ejection fraction (Class I, Level of Evidence A) 2
• Beta-blockers are recommended for all patients with reduced ejection fraction 2

Second-Line Therapies

• Mineralocorticoid receptor antagonists (MRAs) such as spironolactone and eplerenone for:

  • Patients with NYHA class III-IV symptoms and LVEF ≤35% 2
  • Patients with mild symptoms (NYHA class II) based on the EMPHASIS-HF trial 3, 4

• Eplerenone specifically has shown:

  • Reduction in mortality and cardiovascular events in post-MI heart failure patients 5, 6
  • Significant benefits starting as early as 26 days after initiation 4
  • Reduction in both death risk and hospitalization risk among patients with mild symptoms 3

• Angiotensin receptor blockers (ARBs) for patients intolerant to ACE inhibitors 2

Clinical Decision-Making Algorithm

For patients with heart failure:

1. Assess ejection fraction and symptom severity

   • For HFrEF: Start with ACE inhibitor and beta-blocker therapy
   • For HFpEF: Limited evidence-based therapies available

2. Add second-line therapy based on clinical status:

   • For NYHA class II-IV with LVEF ≤35%: Add mineralocorticoid receptor antagonist (spironolactone or eplerenone)
   • For post-MI heart failure: Consider eplerenone specifically

3. Consider device therapy when appropriate:

   • ICD for patients with LVEF ≤35% and NYHA Class II-III symptoms 7
   • CRT for patients with LVEF ≤35% and QRS duration ≥150ms with LBBB morphology 7

Important Considerations and Monitoring

• Regular monitoring of renal function and electrolytes is essential, particularly with MRAs due to risk of hyperkalemia 5, 6
• Eplerenone is contraindicated with potent CYP3A4 inhibitors due to increased hyperkalemia risk 6
• Patients with reduced renal function and diabetes are at highest risk for hyperkalemia with MRAs 6

Conclusion

While eplontersen shows promise for cardiac involvement in hereditary transthyretin amyloidosis, there is currently insufficient evidence to recommend it for general heart failure treatment. Clinicians should continue to follow established heart failure treatment guidelines using ACE inhibitors, beta-blockers, and MRAs as the foundation of therapy, with eplerenone being a well-established MRA option for appropriate patients.