Angiotensin Receptor Neprilysin Inhibitors in HFrEF: Is This the First Disease Modifying Therapy Drug Class Leading to a Substantial Reduction in Diuretic Need?

Despite significant advances in disease modifying therapy in heart failure (HF), diuretics have remained the cornerstone of volume management in all HF phenotypes. Diuretics, alongside their definite acute haemodynamic and symptomatic benefits, also possess many possible deleterious side effects. Moreover, questions remain regarding the prognostic impact of chronic diuretic use. To date, few data exist pertaining to diuretic reduction as a result of individual traditional guideline directed medical therapy in HF with reduced ejection fraction (HFrEF). However, diuretic reduction has been demonstrated with sacubitril/valsartan (angiotensin receptor-neprilysin inhibitor [ARNi]) from the PARADIGM study, as well as, post-marketing reports from our own group and others. Whether the ARNi compound represents the dawn of a new era, where effective therapies will have a more noticeable reduction on diuretic need, remains to be seen. The emergence of sodium glucose transport 2 inhibitors and guanylate cyclase stimulators may further exemplify this issue and potentially extend this benefit to HF patients outside of the HFrEF phenotype. In conclusion, emerging new therapies in HFrEF could reduce the reliance on diuretics in the management of this phenotype of HF. These developments further highlight the clinical importance to continually assess an individual's diuretic requirements through careful volume assessment.