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Entresto: added value in heart failure?


The combined sacubitril/valsartan molecule (Entresto®) has been authorised in Europe since 2015 for the treatment of symptomatic heart failure with reduced ejection fraction. Since Entresto is considerably more expensive than the generically available agents used in heart failure, treatment with Entresto should offer significant advantages over existing agents. As regards the authorised indication (chronic symptomatic heart failure with reduced ejection fraction), this has been investigated in one large randomised study with an actively treated control group. Entresto led to a convincing statistically significant and clinically relevant reduction of cardiovascular mortality or hospitalization due to heart failure (composite endpoint). However, critical questions about the quality of the study design have remained unanswered.


  • At a maximum dosage of 200 mg daily, Entresto is superior to enalapril at a maximum dosage of 10 mg twice daily to treat chronic symptomatic heart failure with reduced ejection fraction.
  • The available scientific evidence for the intended patient population has relevant shortcomings, limiting the applicability of Entresto.
  • One of the main points of criticism is that the control group in the authorisation study was not treated at the maximum dosage of enalapril recommended in the guidelines, 20 mg twice daily.
  • Treatment with Entresto should be reserved for patients who remain symptomatic despite receiving the optimal standard treatment titrated to the recommended maximum dosage. 

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Authors

  • Sander van den Bogert, dr, pharmacist