"Heart failure is a major international public health problem presenting significant medical and economic challenges. In the United States, HF has high prevalence (greater than 5 million individuals), high incidence (550,000 new cases yearly), increasing hospitalization rates (400,000 in 1979 to greater than 1 million in 2004), and exorbitant cost (estimated to exceed $33 billion in 2007). 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. Patients hospitalized with AHFS have poor overall prognosis," the authors write. Given the negative results in terms of efficacy and safety of drugs tested so far in this setting, "an unmet need exists for more effective and safe strategies to treat AHFS."
Mihai Gheorghiade, M.D., of Northwestern University, Feinberg School of Medicine, Chicago, and colleagues with the EVEREST trial from sites in North America, Europe and South America, evaluated whether treatment of heart failure with tolvaptan, in addition to standard therapy including diuretics, would result in clinical improvements during the inpatient period. Two trials were conducted during the inpatient period of EVEREST. A total of 2,048 (trial A) and 2,085 (trial B) patients hospitalized with heart failure and congestion were studied. Patients received either tolvaptan (30 mg/d) or matching placebo, within 48 hours of admission.
Analysis of the primary outcome (combined changes in clinical status and body weight) showed significantly greater improvement in the tolvaptan groups than in the placebo groups. Average body weight reduction was greater with tolvaptan on day 1 and day 7 or discharge, whereas improvements in global clinical status were not different between groups. In both trials, more patients in the tolvaptan groups reported an improvement in dyspnea when compared with the placebo groups. Edema at day 7 or discharge improved significantly with tolvaptan in trial B but did not reach significance in trial A. Serious adverse event frequencies were similar between groups, without excess in kidney failure or hypotension (abnormally low blood pressure).
"These 2 trials demonstrate in a reproducible manner that tolvaptan, when added to standard therapy including diuretics, improves many, though not all, of the signs and symptoms of HF, as assessed by both patients and physicians, and reduces body weight throughout hospitalization. These positive effects were achieved without adversely affecting heart rate, blood pressure, or serum electrolytes," the authors write. -JAMA and Archives Journals
