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Heart Failure Population with Therapeutic Response to Sacubitril/Valsartan, Spironolactone and Candesartan: FDA

Charu Gandotra1, Jennifer Clark2, Ququan Liu2

  • 1Office of New Drugs, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, MD, USA. charu.gandotra@fda.hhs.gov.

Therapeutic Innovation & Regulatory Science
|October 26, 2021
PubMed

Insights

Sacubitril/valsartan effectively treats chronic heart failure across a spectrum of ejection fractions, not just reduced ejection fraction. Clinical judgment is key for optimal patient selection beyond strict LVEF cutoffs.

Area of Science:

  • Cardiology
  • Pharmacology
  • Clinical Trials

Background:

  • Sacubitril/valsartan is approved for heart failure with reduced ejection fraction (HFrEF) based on the PARADIGM-HF trial.
  • The PARAGON-HF trial investigated its efficacy in heart failure with preserved ejection fraction (HFpEF).

Purpose of the Study:

  • To evaluate the rationale for a revised indication of sacubitril/valsartan.
  • To emphasize the need for a nuanced approach to heart failure classification beyond traditional LVEF cutoffs.

Main Methods:

  • Analysis of the PARADIGM-HF and PARAGON-HF trial data.
  • Evaluation of sacubitril/valsartan efficacy across a continuous spectrum of left ventricular ejection fraction (LVEF).

Main Results:

  • PARAGON-HF did not meet its primary endpoint for HFpEF.
  • Analysis showed sacubitril/valsartan efficacy in patients with mildly reduced LVEF, similar to HFrEF patients.
  • A broader indication was established, recommending clinical judgment for treatment decisions.

Conclusions:

  • Sacubitril/valsartan benefits extend to patients with LVEF below normal, not strictly defined by HFpEF criteria.
  • The product label does not specifically refer to HFpEF, highlighting the importance of continuous LVEF assessment.

Keywords:
Heart failureHeart failure with preserved ejection fractionHeart failure with reduced ejection fractionLeft ventricular ejection fractionSacubitril/valsartan

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