Introduction: Heart failure (HF) is characterized by maladaptive neurohormonal activation of the cardiovascular and renal systems resulting in circulatory inadequacy and frequent acute exacerbations. The increasing burden of HF prompted investigation of underlying pathophysiological mechanisms and the design of pharmacotherapeutics that would target these pathways.

Areas covered: A MEDLINE search for relevant original investigations and review articles of newer hormonal drugs for HF since the year 2005 till October 2017 provided us with necessary literature. Major trials and relevant clinical investigations were discussed.

Expert commentary: A multitude of hormonal pathways central to HF were identified, including the natriuretic peptide system and neurohormones such as relaxin, arginine vasopressin, and endothelin. However, drugs targeting these novel pathways (aliskiren, tolvaptan, ularitide, serelaxin, bosentan, macitentan) failed to show mortality benefit. This emphasizes a tremendous unmet need in the pharmacotherapy for HF, especially for the subtypes of acute HF and HF with preserved ejection fraction. Sacubitril/valsartan demonstrated substantial mortality benefit in chronic systolic HF population and is endorsed by international HF guidelines. If proven to be efficacious in larger outcome trials, finerenone can be a valuable addition baseline HF therapy. More basic, translational, and phenotype specific clinical research is warranted to improve HF pharmacotherapy.