Safety and Efficacy of Istaroxime 1.0 and 1.5 µg/kg/min for Patients with Pre Cardiogenic Shock

Introduction: Istaroxime was shown in a small study to increase systolic blood pressure (SBP) in patients with pre-cardiogenic shock (CS) due to acute heart failure (AHF). Objectives: In the current analysis we describe the effects of two doses of istaroxime 1.0 (Ista-1) and 1.5 µg/kg/min (Ista-1.5). Methods: The target dose of istaroxime, administered in a double-blind placebo-controlled fashion, was 1.5 µg/kg/min in the first cohort (n=24) and was reduced to 1.0 µg/kg/min in subsequent patients (n =36). Results: Ista-1 was associated with numerically larger effects on SBP area under the curve with a 93.6% relative increase from baseline during the first 6 hours with Ista-1 vs. 39.5% for Ista-1.5, and with a 49.4% and 24.3% relative increase, respectively, at 24 hours. Compared to placebo, Ista-1.5 had more worsening HF events to day 5 and fewer days alive out of hospital (DAOH) through day 30. Ista-1 had no worsening HF events and DAOH to day 30 were significantly increased. Effects on echocardiographic measures were similar although decrease in left ventricular end systolic and diastolic volumes was numerically larger in the Ista-1. Ista-1, but not Ista-1.5, had numerically smaller creatinine increase and larger decrease in natriuretic peptides as compared to placebo. There were 5 serious adverse events in Ista-1.5 (4 of which cardiac) but only 1 in Ista-1. Conclusions: In patients with pre-CS due to AHF, istaroxime 1.0 µg/kg/min induced beneficial effects on SBP, and DAOH. Clinical benefits appear to be reached at doses less than 1.5 ug/kg/min.