Efficacy and Safety of the Vasopressin V1A/V2-Receptor Antagonist Conivaptan in Acute Decompensated Heart Failure: A Dose-Ranging Pilot Study

Background: Hospitalization for acute decompensated heart failure (ADHF) involves substantial morbidity and mortality. Current management strategies have major limitations, and there has been little progress in the development of newer therapies. Arginine vasopressin-receptor antagonists may have promise in the treatment of ADHF in view of their ability to facilitate diuresis. This pilot study was designed to evaluate the efficacy and safety of intravenous conivaptan, a dual arginine vasopressin V_1A/V₂-receptor antagonist, in treating ADHF. Methods and Results: In a double-blind, multicenter trial, 170 patients hospitalized for worsening heart failure and given standard therapy were randomly assigned to treatment with conivaptan (20-mg loading dose followed by 2 successive 24-hour continuous infusions of 40, 80, or 120 mg/d) or placebo. The conivaptan and placebo groups did not differ significantly in patient or clinician assessments of global and respiratory status at 48 hours. There was no evidence of worsening heart failure in any group. Conivaptan at each dosage increased urine output significantly more than placebo at 24 hours (P ≤ .02), with the difference averaging 1.0 to 1.5 L. Decreases in mean body weight with conivaptan 40 and 80 mg/d (∼ 1-2 kg) paralleled the increases in urine output but did not reach statistical significance. Conivaptan was well tolerated and not associated with clinically important changes in vital signs, electrolyte disturbances, or cardiac rhythm. The most common adverse events were infusion-site reactions. Conclusion: When added to standard therapy for ADHF, conivaptan safely improves urine output. Further study of this compound in ADHF may be warranted, especially in view of the limitations of current treatment for this syndrome.