Abstract 15858: The Aquaretic Effect of Lixivaptan in Patients With Heart Failure and Volume Overload
Introduction: Lixivaptan is a selective, orally active V2 receptor antagonist with potent aquaretic effect.
Hypothesis: Patients with heart failure (HF) and volume overload will benefit from the aquaretic action of lixivaptan.
Methods: A phase 2, multicenter, randomized, double-blind, placebo-controlled study of 100mg oral lixivaptan in outpatients with heart failure and volume overload on standard treatment that includes diuretics for a minimum of 30 days. Documentation of volume overload required the presence of at least one of the following: Dyspnea, rales, edema, elevated jugular venous pressure, congestion on chest x-ray or elevated BNP ≥ 150 pg/ml or NT pro-BNP ≥ 450 pg/ml within 48 hr of randomization. The primary endpoint was the mean change in body weight from baseline to day 1. Several secondary endpoints were also assessed. Patients were randomly assigned (2:1) to lixivaptan (n=111) or placebo (n=59). The 8 week study period was completed by 88 (79%) and 43 (73%) of lixivaptan and placebo patients, respectively. Baseline characteristics are shown in table. Mean change in body weight from baseline to day 1was a loss of 0.38±0.08kg with lixivaptan and a gain of 0.13±0.11kg (P=<0.001) in the placebo group. The difference from placebo in patients with LVEF<40% (n=96) was -0.52kg (P=0.07) and in patients with left ventricular ejection fraction (LVEF) ≥40% (n=74) -0.55kg (P=0.08). Of the secondary endpoints, by week 2, dyspnea improved in 42% of lixivaptan and 24% of placebo patients, (P=0.027) and orthopnea in 26% of lixivaptan and 13% of placebo patients (P=0.013).
Conclusion: Lixivaptan 100mg significantly reduced body weight from baseline to day 1 in outpatients with heart failure and volume overload to a similar extent in patients with preserved or reduced LVEF. Its potential use in the treatment of HF should be further explored.
- © 2011 by American Heart Association, Inc.