Randomized double‐blind clinical studies of ularitide and other vasoactive substances in acute decompensated heart failure: a systematic review and meta‐analysis

AIMS: Acute decompensated heart failure (ADHF) has a poor prognosis and limited treatment options. No direct comparisons between ularitide—a synthetic natriuretic peptide being evaluated in ADHF—and other vasoactive substances are available. The aim of this meta‐analysis was to determine haemodynamic effect sizes from randomized double‐blind trials in ADHF. METHODS AND RESULTS: Eligible studies enrolled patients with ADHF requiring hospitalization and haemodynamic monitoring. Patients received 24–48 h of infusion with a vasoactive substance or comparator. Primary outcome measure was pulmonary artery wedge pressure (PAWP). Treatment effects were quantified as changes from baseline using mean differences between study drug and comparator. Results were analysed using random‐effects (primary analysis) and fixed‐effects meta‐analyses. Twelve randomized, double‐blind studies were identified with data after 3, 6, and 24 h of treatment (n = 622, 644, and 644, respectively). At 6 h, significant PAWP benefits for ularitide over placebo were seen (Hedges' g effect size, −0.979; P < 0.0001). On meta‐analysis, treatment difference between ularitide and pooled other agents was statistically significant (−0.501; P = 0.0303). Effect sizes were numerically higher with ularitide than other treatments at 3 and 24 h. After 6 h, a significant difference in effect size between ularitide and all other treatments was observed for right atrial pressure (Hedges' g, −0.797 for ularitide and −0.304 for other treatments; P = 0.0274). CONCLUSIONS: After 6 h, ularitide demonstrated high effect sizes for PAWP and right atrial pressure. Improvements in these parameters were greater with ularitide vs. pooled data for other vasoactive drugs.