The effect of Pecavaptan in patients with heart failure with reduced versus preserved ejection fraction - a post hoc analysis of the AVANTI trial
G H D Voordes, D Ceelen, K Damman, L Cosic, S R Goldsmith, D Burkhoff, F Gustafsson, R Frost, K Duarte, L Monzo, N Girerd, J M Ter Maaten, F Zannad, J E Udelson, A A VoorsAbstract
Introduction
Pecavaptan, a dual V1a/V2 vasopressin receptor antagonist showed modest short term effects on weight, peripheral edema and dyspnea, without impacting change in serum creatinine and weight at 30 day in heart failure (HF). In this post-hoc analysis we explore the effects of pecavaptan in HF-patients with reduced (HFrEF), -mildly reduced (HFmrEF) and preserved ejection fraction (HFpEF).
Methods
AVANTI was a double-blind, randomized, placebo-controlled trial in patients with acute HF, who received either standard of care (SoC) + placebo or SoC + pecavaptan for 30 days. HFrEF was defined as LVEF ≤40%, a LVEF >40% was classified as HFmrEF/HFpEF. Linear mixed models with estimated marginal means and multivariate regression were used to examine the effect of HF-type on changes in weight and creatinine.
Results
A total of 293 patients with HFrEF and 186 patients with HFmrEF/HFpEF were included. After 7 days, pecavaptan caused modest placebo-adjusted reduction in weight in HFrEF(-0.83, 95% CI -1.41 to -0.26 kg, p = 0.004), but not in HFmrEF/HFpEF (0.03, 95% CI 0.74 to -0.81 kg, p = 0.934; interaction p = 0.087). The placebo-adjusted creatinine to weight loss response to pecavaptan at day 7 was greater in HFrEF compared to HFmrEF/HFpEF (β = -1.15, p = 0.002, interaction p = 0.008).
Conclusion
Pecavaptan treatment resulted in significant weight reduction in HFrEF but not HFmrEF/HFpEF. Pecavaptan induced significant weight loss with limited serum creatinine change compared to placebo, but only in HFrEF.For image description, please refer to the figure legend and surrounding text.For image description, please refer to the figure legend and surrounding text.