Insights into foundational therapies for heart failure with reduced ejection fraction

In this review, we discuss what is meant by "foundational" therapy for patients with heart failure and reduced ejection fraction (HFrEF) and the evidence supporting the use of the five agents that comprise this group of drugs i.e., sacubitril/valsartan, a beta-blocker, an aldosterone or mineralocorticoid receptor antagonist (MRA) and a sodium-glucose cotransporter 2 (SGLT2) inhibitor. We review the conventional approach to sequencing these therapies in HFrEF and proposed new rapid sequencing strategies. We review a recent modelling study suggesting the optimal sequence of treatment includes a sodium-glucose cotransporter 2 inhibition and an MRA as the first two therapies. Finally, we review the important opportunity offered by hospitalization for worsening heart failure to initiate and optimize foundational therapies in patients at high risk of early adverse outcomes.