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for the Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study With Tolvaptan (EVEREST) Investigators HEART FAILURE (HF) IS A MAjor international public health problem presenting significant medical and economic challenges. In the United States, HF has high prevalence (Ͼ5 million individuals), high incidence (550 000 new cases yearly), increasing hospitalization rates (400 000 in 1979 to Ͼ1 million in 2004), and exorbitant cost (estimated to exceed $33 billion in 2007). 1 A considerable share of the burden of HF is accounted for by the acute HF syndromes (AHFS), defined as conditions with gradual or rapid changes in the signs and symptoms of HF that require urgent therapy. 2 Patients hospi-talized with AHFS have poor overall prognosis. [3][4][5][6][7][8] Congestion characterized by dyspnea, edema, rales, jugular venous dis-See also pp 1319 and 1374.

MD; for the Tolvaptan InvestigatorsBackground-In this study, we evaluated the effects of tolvaptan (OPC-41061), a novel, oral, nonpeptide vasopressin V 2 -receptor antagonist in patients with chronic heart failure (CHF). Methods and Results-This was a double-blind study investigating the effects of three doses of tolvaptan and placebo in patients with CHF. After a run-in period, 254 patients were randomly assigned to placebo (nϭ63) or tolvaptan [30 mg (nϭ64), 45 mg (nϭ64), or 60 mg (nϭ63)] once daily for 25 days. Patients were not fluid-restricted and were maintained on stable doses of furosemide. At day 1, when compared with baseline, a decrease in body weight of Ϫ0.79Ϯ0.99, Ϫ0.96Ϯ0.93, and Ϫ0.84Ϯ0.02 kg was observed in the 30-, 45-, and 60-mg tolvaptan groups, respectively, and a body weight increase of ϩ0.32Ϯ0.46 kg in the placebo group (PϽ0.001 for all treatment groups versus placebo). Although the initial decrease in body weight was maintained during the study, no further reduction was observed beyond the first day. An increase in urine volume was observed with tolvaptan when compared with placebo (3.9Ϯ0.6, 4.2Ϯ0.9, 4.6Ϯ0.4, and 2.3Ϯ0.2 L/24 hours at day 1 for 30-, 45-, and 60-mg tolvaptan groups, and placebo, respectively; PϽ0.001). A decrease in edema and a normalization of serum sodium in patients with hyponatremia were observed in the tolvaptan group but not in the placebo group. No significant changes in heart rate, blood pressure, serum potassium, or renal function were observed. Conclusions-In patients with CHF, tolvaptan was well tolerated; it reduced body weight and edema and normalized serum sodium in the hyponatremic patients.