Safety and efficacy intravenous istaroxime up to 60 hours for patients with pre-cardiogenic shock.

Abstract

Background and aims: A drug that improves blood pressure 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 systolic blood pressure (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 for wedge pressure, 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 arrhythmias 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 reductions in wedge pressure and heart rate without increases in arrhythmias.