Istaroxime: A Novel Therapeutic Agent for Acute Heart Failure

Acute decompensated heart failure (ADHF) is a multifactorial process that is associated with high morbidity and mortality. Treatment with inotropes can rapidly improve hemodynamic status; however, their use has been associated with increased mortality and incidence of arrhythmias. Istaroxime is a first-in-class intravenous agent currently undergoing clinical trials for acute heart failure. It has the unique mechanism of action of both Na+/K+ ATPase inhibition and sarcoplasmic/endoplasmic reticulum Ca2+ ATPase 2a stimulation. Notably, its action on sarcoplasmic/endoplasmic reticulum Ca2+ ATPase 2a improves calcium handling, which is known to be abnormal in heart failure. Clinical trials have shown that istaroxime has beneficial hemodynamic effects; in particular, its ability to increase systolic blood pressure without causing significant increases in heart rate or clinically significant arrhythmias differentiates it from inotropes currently utilized for ADHF treatment, such as milrinone. While initial studies are encouraging, additional trials are needed to assess outcomes and to compare their performance to standard inotropes in patients hospitalized with ADHF. This article will review the relevant preclinical and clinical trials for istaroxime, as well as the relevant pharmacology.