Istaroxime for Patients with Acute Heart Failure: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Abstract

Istaroxime, an intravenous inotropic agent with a dual mechanism—increasing both cardiomyocyte contractility and relaxation—is a novel treatment for acute heart failure (AHF), the leading cause of morbidity and mortality in heart failure. We conducted a systematic review and meta-analysis that synthesized randomized controlled trials (RCTs), which were retrieved by systematically searching PubMed, Web of Science, SCOPUS, and Cochrane until 24 April 2023. We used a fixed-effect or random-effect model—according to heterogeneity—to pool dichotomous data using the risk ratio (RR) and continuous data using the mean difference (MD), with a 95% confidence interval (CI). We included three RCTs with a total of 300 patients. Istaroxime was significantly associated with an increased left ventricular ejection fraction (mL) (MD: 1.06, 95% CI: 0.29, 1.82; p = 0.007), stroke volume index (MD: 3.04, 95% CI: 2.41, 3.67; p = 0.00001), and cardiac index (L/min/m2) (MD: 0.18, 95% CI: 0.11, 025; p = 0.00001). Also, istaroxime was significantly associated with a decreased E/A ratio (MD: −0.39, 95% CI: −0.58, −0.19; p = 0.0001) and pulmonary artery systolic pressure (mmHg) (MD: 2.30, 95% CI: 3.20, 1.40; p = 0.00001). Istaroxime was significantly associated with increased systolic blood pressure (mmHg) (MD: 5.32, 95% CI: 2.28, 8.37; p = 0.0006) and decreased heart rate (bpm) (MD: −3.05, 95% CI: −5.27, −0.82; p = 0.007). Since istaroxime improved hemodynamic and echocardiographic parameters, it constitutes a promising strategy for AHF management. However, the current literature is limited to a small number of RCTs, warranting further large-scale phase III trials before clinical endorsement.

Soluble guanylate cyclase stimulators for heart failure: a network meta-analysis and subgroup analyses of reduced and preserved ejection fraction

“…sGC stimulators work by increasing the levels of cyclic guanosine monophosphate in the body, leading to vasodilation and improved blood flow. This mechanism of action differs from traditional HF drugs, such as angiotensin-converting enzyme inhibitors (ACEIs), istaroxime, and beta-blockers (BBs), which target different pathways in the body [ 4 , 5 ].…”