Rationale and study design for a multicenter, randomized, double-blind, placebo-controlled study of the effects of tolvaptan on the acute and chronic outcomes of patients hospitalized with worsening congestive heart failure

The identification of novel approaches for the treatment of volume overload in patients with heart failure is urgently needed. The current standard of care for this population involves the administration of loop diuretics. It is well documented that high doses of these agents increase the activity of the renin-angiotensin system; in addition, the use of loop diuretics in the setting of heart failure may increase the risk of arrhythmic death caused by electrolyte depletion, and decrease the patient's tolerability of life-saving therapies such as ACE inhibitors. The introduction of the mechanism of V₂ antagonism holds promise for the treatment of exacerbations of chronic heart failure and provides a rational approach to therapy in the acute setting of this disease. This treatment approach, however, must be supported by data from controlled clinical trials that demonstrate the safety of V₂ antagonism as a therapeutic measure and its association with improvements in clinical outcomes. In this regard, the ACTIV in CHF trial makes an important contribution to heart failure research, and its findings will offer insight into the future role of vasopressin antagonism in the treatment of heart failure.