Safety and Efficacy Intravenous Istaroxime up to 60 hours for Patients with Pre-Cardiogenic Shock

Background and aims: A drug that improves blood pressure (BP) and cardiac output (CO) while reducing pulmonary wedge pressure safely is needed for patients with cardiogenic shock (CS) due to acute heart failure (AHF). Methods: In a randomized, double-blind, placebo-controlled trial, istaroxime 0.5 to 1.5 µg/kg/min for 24 - 60 hours was administered to 48 patients, and placebo to 42 patients, with pre-CS due to AHF under hemodynamic monitoring. Echocardiographic, and Holter monitoring were done in both parts. Results: Patients randomized to istaroxime had a greater increase in SBP during the first 6 hours (primary endpoint), ls-mean (SE) 62.0 (6.59) mmHg*hour vs 36.4 (7.11) in the placebo arm (LS mean difference of 25.6 mmHg*hour, 95% CI 7.2-44.0 mmHg*h, p= 0.007). In patients administered istaroxime for at least 48 hours SBP increase persisted for 60 hours. Istaroxime led to a greater increase in CO (0.66 L/min, p=0.017) and decrease in wedge pressure (3.8 mmHg, p=0.0017). Relative to average baselines of 3.6 L/min for CO and 22.5 mmHg, this translates into improvements of 18.3% and 16.9%. respectively. Echocardiographic assessments showed improvements in E/A, TAPSE, and LA volume at 24 hours. There were improvements in eGFR at 24-72 hours and NYHA class to 72 hours. NT-proBNP increased more in istaroxime-treated patients. Heart rate decreased more in the first 24 hours in istaroxime-treated patients. No significant malignant arrythmias were detected in patients treated with istaroxime on Holter monitoring. Conclusions: In this small study, istaroxime doses of up to 1.0 µg/kg/min for up to 60 hours were associated with improvements in SBP, CO and reduction in wedge pressure and heart rate without increase in arrythmias.