What the near Future Holds for Sacubitril/Valsartan: A Summary of Major Ongoing Studies.

Hisham A Badreldin,Taif Almutairi,Awatif Hafiz,Nasser Aldosari,Lama Alnashwan,Nada Yousif,Ohoud Aljuhani,Omar Alshaya,Khalid Alsulaiman

doi:10.3390/jcdd9020054

Abstract

Early research on neprilysin inhibition showed that sacubitril/valsartan, a combination of the valsartan and the neprilysin inhibitor sacubitril, was superior to enalapril in patients with heart failure with reduced ejection fraction (HFrEF) in the PARADIGM-HF study in 2014. Therefore, for patients with HFrEF, worldwide recommendations have been reformed to include sacubitril/valsartan. In addition, sacubitril/valsartan has been investigated in other cardiovascular disease states, such as patients with heart failure and preserved ejection fraction (HFpEF) and following myocardial infarction (MI) events. In February 2021, the FDA expanded the indication use of sacubitril/valsartan to include the HFpEF patient population based on the results of the PARAGON-HF trial. However, randomized clinical trials post-MI did not show promising results. Sacubitril/valsartan is currently being investigated in many other cardiovascular and non-cardiovascular conditions. This review aims to shed light and summarize the ongoing sacubitril/valsartan registered studies on the United States National Library of Medicine clinical trials registry.

Highlights

Several pharmacotherapeutic agents emerged over the past few years, and they were able to reshape the modality with which we manage patients with heart failure (HF)
This study found that sacubitril/valsartan had better outcomes, such as a higher reduction in the N-terminal pro-brain natriuretic peptide (NT-proBNP) concentration than enalapril therapy [3]
After the publication of the PARAGON-HF trial, the question remains if long-term use of sacubitril/valsartan has any prognostic benefits in preventing acute coronary syndrome in heart failure and preserved ejection fraction (HFpEF) patients

Summary

Introduction

Several pharmacotherapeutic agents emerged over the past few years, and they were able to reshape the modality with which we manage patients with heart failure (HF). The PARADIGM-HF study showed that sacubitril/valsartan was significantly more effective in reducing the risk of death from CV causes compared to enalapril [2]. On 1 September 2019, the PARAGON-HF trial concluded that in patients with HF and an ejection fraction of 45% or higher, the addition of sacubitril/valsartan did not result in significantly decreased rates of total hospitalizations for HF or death from CV causes [4]. After the publication of the PARAGON-HF trial, the question remains if long-term use of sacubitril/valsartan has any prognostic benefits in preventing acute coronary syndrome in HFpEF patients. This question deserves further investigation, especially as a sub-analysis of the PARAGON-HF trial showed beneficial effects in female patients and those with an LVEF between 45% and

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