Acute hemodynamic effects of conivaptan, a dual V1A and V2 vasopressin receptor antagonist, in patients with advanced heart failure

Background-Arginine vasopressin may contribute to abnormalities in hemodynamics and fluid balance in heart failure through its actions on V-1A (vascular and myocardial effects) and V-2 receptors (renal effects). Inhibiting the action of vasopressin may be beneficial in patients with heart failure. Methods and Results-A total of 142 patients with symptomatic heart failure (New York Heart Association class III and IV) were randomized to double-blind, short-term treatment with conivaptan, a dual V-1a/V-2 vasopressin receptor antagonist, at a single intravenous dose (10, 20, or 40 in mg) or placebo, Compared with placebo, conivaptan at 20 and 40 mg significantly reduced pulmonary capillary wedge pressure (-2.6 +/-0.7, -5.4 +/-0.7, and -4.6 +/-0.7 mm Hg for placebo and 20 and 40 mg groups, respectively; P <0.05) and right atrial pressure (-2.0 +/-0.4, -3.7 +/-0.4, and -3.5 +/-0.4 mm Hg for placebo and 20 and 40 mg groups, respectively; P <0.05) during the 3- to 6-hour interval after intravenous administration. Conivaptan significantly increased urine output in a dose-dependent manner (-11 +/- 17, 68 +/- 17, 152 +/- 19, and 176 +/- 18 mL/hour for placebo and 10, 20, and 40 mg groups, respectively; P <0.001) during the first 4 hours after the dose. Changes in cardiac index, systemic and pulmonary vascular resistance, blood pressure, and heart rate did not significantly differ from placebo. Conclusions-In patients with advanced heart failure, vasopressin receptor antagonism with conivaptan resulted in favorable changes in hemodynamics and urine output without affecting blood pressure or heart rate. These data suggest that vasopressin is functionally significant in advanced heart failure and that further investigations are warranted to examine the effects of conivaptan on symptom relief and natural history in such patients.