First non-adrenergic drug to show benefit on BP in pre-cardiogenic shock

In a pilot study, istaroxime significantly increased the systolic blood pressure (SBP) of patients with pre-cardiogenic shock. The agent was well-tolerated and was not associated with worsening arrhythmias or renal function. These results encourage further investigation of this non-adrenergic agent.

“Istaroxime was designed to improve both systolic contraction and diastolic relaxation,” clarified Prof. Marco Metra (University of Brescia, Italy) [1]. The current randomised, double-blind, placebo-controlled pilot study, named SEISMiC (NCT04325035) included 60 patients with Society for Cardiovascular Angiography and Interventions (SCAI) stage B cardiogenic shock and assessed the efficacy and safety of 24-hour infusion of istaroxime in this population. The primary endpoint was the change in the Area Under Curve (AUC) for SBP over 6 hours.

Patients on istaroxime had a significantly larger increase in SBP AUC over 6 hours compared to placebo (44.6mmHg/hr vs 28.1; P=0.017). After withdrawal from istaroxime, the SBP of patients who had received this agent returned to the level of placebo-receivers. The investigators did not observe differences in heart rate alterations between patients in the experimental arm and those in the placebo arm nor was there any evidence of an adverse effect of istaroxime on renal function. Furthermore, echocardiographic parameters displayed a benefit of istaroxime over placebo: Cardiac Index change from baseline 0.16 vs -0.057, P=0.016; left ventricle end-diastolic volume: -6.51 ml vs 5.64 ml, P=0.034; left atrium area -1.82 cm² vs 0.04 cm², P=0.008).

In total, 6 serious adverse events (AEs) were reported per study group. Adverse drug reactions occurred in 52% of the patients, mostly being gastrointestinal complaints (31%) or infusion site pain (14%). Notably, serious AEs occurred only in patients receiving 1.5 μg/kg/min, but not in patients receiving 1.0 μg/kg/min, while the haemodynamic effects of istaroxime were similar.

“This study supports the continuance of the development of istaroxime as a potential treatment for both acute heart failure and cardiogenic shock,” concluded Prof. Metra.

1. 
   
   1. Metra M, et al. A multicenter, randomized, double-blind, placebo-controlled, parallel-group study on the safety and efficacy of istaroxime for pre-cardiogenic shock (SEISMiC). LBT 2, Heart Failure 2022, 21–24 May, Madrid, Spain.

 

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Posted on 24 May, 202213 June, 2022