Early changes in dyspnea with 24-h istaroxime infusion among patients with acute heart failure.

BACKGROUND: We evaluated the effects of a 24-h istaroxime infusion on changes in self-reported dyspnea among patients with acute heart failure (AHF). METHODS: Patients hospitalized for AHF with ejection fraction ≤40 were randomized to receive a 24-h infusion of placebo or istaroxime at doses of 0.5 (Ista-0.5) or 1.0 μg/kg/min (Ista-1.0). Self-reported dyspnea was assessed by means of a visual analogue scale (VAS). Dyspnea VAS area under the curve (AUC) and changes in VAS dyspnea from baseline through 24 and 48 h were compared between istaroxime- and placebo-treated patients. RESULTS: Among 113 AHF patients (n = 39 placebo, n = 39 Ista-0.5, n = 35 Ista-1.0), a statistically significant difference in dyspnea VAS AUC from baseline through 24 h was observed in the pooled istaroxime arm vs. the placebo arm [win odds 1.44, 95% confidence interval (CI) 1.00 to 2.07; P = 0.048], with similar findings for Ista-0.5 vs. placebo (win odds 1.48, 95% CI 1.01 to 2.18; P = 0.047). Win odds consistently favored istaroxime through 48 h, though significance was not maintained. Results were numerically more pronounced among patients with baseline dyspnea VAS < 80, particularly for Ista-0.5 vs. placebo (win odds 1.71, 95% CI 0.76 to 3.83; P = 0.172). Consistent findings were observed changes in dyspnea VAS through 24 h, with a least square mean difference of 2.6 points (95% CI -1.8 to 7.0) between Ista-1.0 and placebo. CONCLUSIONS: Among patients with AHF, 24-h istaroxime infusion was associated with a significantly higher probability of dyspnea improvement compared with placebo through 24 h, with results being numerically more pronounced among patients with worse dyspnea at baseline.