Effect of low-dose administration of carperitide for acute heart failure: the LASCAR-AHF trial

AIMS: The effects of low-dose carperitide on long-term clinical outcomes of patients with acute heart failure (AHF) have not yet been fully elucidated. This study aimed to evaluate the effects of low-dose intravenous carperitide on the long-term clinical outcomes of patients with AHF. METHODS AND RESULTS: In this multicentre, open-label, randomized controlled trial, 247 patients with AHF received low-dose carperitide intravenously with standard treatment or matching standard treatment for 72 h from November 2014 to March 2021 across nine sites in Japan. The primary endpoint was a composite of all-cause death and heart failure hospitalization within 2 years. The primary endpoint was observed in 36 of 122 patients (29.5%) and 35 of 125 patients (28.0%) in the carperitide group and standard treatment groups, respectively [hazard ratio 1.26; 95% confidence interval (CI) 0.78-2.06, P = 0.827]. No significant differences were observed in the secondary endpoints, including cumulative urine volume at 72 h; change in the degree of dyspnoea over 72 h; and changes in brain natriuretic peptide, cystatin C, renin, aldosterone, and catecholamine levels at 72 h post-randomization between the groups. A greater decrease in the estimated glomerular filtration rate was observed in the carperitide group compared with the standard treatment group (inter-group difference -3.9 mL/min/1.73 m2; 95% CI -7.0 to -0.8). CONCLUSION: In patients with AHF, low-dose carperitide did not reduce long-term mortality or hospitalization events when combined with standard treatment. Because patient enrolment was terminated prematurely, the study was underpowered and inconclusive.