Evaluating sacubitril/valsartan as a treatment option for heart failure with reduced ejection fraction and preserved ejection fraction

ABSTRACT

Introduction

Sacubitril/valsartan is the first-in-class angiotensin-receptor neprilysin inhibitor approved in 2015 for the treatment of heart failure with reduced ejection fraction (HFrEF). On 16 February 2021, the Food and Drug Administration acknowledged that “Benefits are most clearly evident in patients with left ventricular ejection fraction below normal,” thus potentially extending the use in subjects with heart failure and preserved ejection fraction (HFpEF).

Areas covered

The authors outline the regulatory history, pharmacokinetics, pharmacodynamics, and risk-benefit profile of sacubitril/valsartan in HFrEF and HFpEF. A critical cross-trial comparison is presented, including sodium-glucose cotransporter 2 inhibitors (SGLT2i), together with an insight into the latest European Society of Cardiology guidelines, where the new category of heart failure with mildly reduced ejection fraction is introduced.

Expert opinion

Sacubitril/valsartan is a foundation of the pharmacological armamentarium in HFrEF to counteract the neuro-hormonal changes and reverse cardiac remodeling, together with beta-blockers, SGLT2i and mineralocorticoid receptor antagonists. The optimal sequence algorithm is an evolving issue, and the authors provide the reader with their personal perspective. A multidisciplinary management is encouraged to minimize the therapeutic inertia and manage tolerability issues, thus supporting adherence. Pragmatic trials, pharmacovigilance, and high-quality real-world evidence are crucial toward personalized safe prescribing of sacubitril/valsartan.

KEYWORDS:

• Sacubitril/valsartan
• heart failure with reduced ejection fraction
• heart failure with preserved ejection fraction
• heart failure with mildly reduced ejection fraction
• European society of cardiology
• pharmacovigilance
• real-world evidence

Drug summary box

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Declaration of Interest

E Raschi reports personal feed for consultancy from Novartis, outside the submitted work. I Diemberger reports speaker fees from Daiichi Sankyo, Boehringer Ingelheim, Pfizer, and Bayer, outside the submitted work. L Potena reports personal fees from Novartis, Biotest, AstraZeneca, Abbott and Sandoz, outside the submitted work. The authors report no other conflicts of interest relevant to this work. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This manuscript was not funded.