Abstract 2732: A Dose-Ranging Pilot Study of Conivaptan in Acute Decompensated Heart Failure
Background: Arginine vasopressin (AVP) plays a key role in water balance and vascular tone, especially under conditions of cardiovascular stress. AVP is inappropriately elevated in patients with acute or chronic heart failure (HF). Acute decompensated HF (ADHF) is characterized primarily by congestion, relief for which conventional diuretics alone are often ineffective. Conivaptan (CNV), a novel AVP V1A- and V2-receptor antagonist, would be expected to produce clinical improvement in ADHF.
Methods: In this multicenter, randomized, double-blind, pilot study, patients hospitalized for ADHF with pulmonary congestion received a CNV 20-mg or placebo (PBO) IV loading dose, followed by CNV 40, 80, or 120 mg/d or PBO by continuous infusion for 2 d. Initiation or change in the infusion rate of diuretics (which were otherwise permitted), vasodilators, or positive inotropes was not allowed during the study. Efficacy variables included area-under-the-curve (AUC) change from baseline in patient-assessed severity of respiratory symptoms using a visual analog scale (VAS), AUC for total urine output, and change from baseline in body weight.
Results: Among 162 treated patients, 63% were men, 65% were white, mean age was 63.5 years, 91% had chronic NYHA class III/IV HF, and the mean left ventricular ejection fraction was 29.5%. CNV significantly increased total urine output vs PBO, and decreased body weight, but did not improve respiratory VAS scores (Table⇓). CNV was well tolerated; most adverse events (AEs) were mild or moderate in severity and related to infusion-site reactions. AEs led to discontinuation of 5 patients given CNV 120 mg/d, 4 given CNV 80 mg/d, and 1 patient in each of the other groups.
Conclusions: CNV increased urine output and decreased body weight; clinical status was not improved according to the VAS. Given the key roles of fluid removal and weight loss in predicting better outcomes in ADHF, results from this pilot study support a formal outcomes study of CNV in ADHF.