Tolvaptan a potentially useful agent for treating HF patients: EVEREST

Adding the oral vasopressin antagonist tolvaptan to standard IV therapy in patients hospitalized with acute decompensated heart failure led to small but significant improvements in some symptoms and clinical signs, but did not result in improvement or reduction in survival nor in the combined end point of cardiovascular mortality or HF hospitalization.The findings of the study were presented at ACC07 by Dr Marvin Konstam (Tufts-New England Medical Center, Boston, MA) in his formal presentation of the Efficacy of Vasopressin Antagonism in Heart Failure Trial (EVEREST). The results were also published online in the Journal of the American Medical Association.An event-driven, randomized, double-blind, placebo-controlled study, the outcome trial comprised 4133 patients within two short-term clinical status studies, who were hospitalized with heart failure, randomized at 359 North American, South American, and European sites, and followed up during long-term treatment.Within 48 hours of admission, patients were randomly assigned to receive oral tolvaptan, 30 mg once per day (n = 2072), or placebo (n = 2061) for a minimum of 60 days, in addition to standard therapy.During a median follow-up of 9.9 months, 537 patients (25.9%) in the tolvaptan group and 543 (26.3%) in the placebo group died (hazard ratio, 0.98; 95% confidence interval [CI], 0.87-1.11; P = .68). The composite of cardiovascular death or hospitalization for heart failure occurred in 871 tolvaptan group patients (42.0%) and 829 placebo group patients (40.2%; hazard ratio, 1.04; 95% CI, 0.95-1.14; P = .55). Secondary end points of cardiovascular mortality, cardiovascular death or hospitalization, and worsening heart failure were also not different. Tolvaptan significantly improved secondary end points of day 1 patient-assessed dyspnea, day 1 body weight, and day 7 edema. In patients with hyponatremia, serum sodium levels significantly increased. The Kansas City Cardiomyopathy Questionnaire overall summary score was not improved at outpatient week 1, but body weight and serum sodium effects persisted long after discharge. Tolvaptan caused increased thirst and dry mouth, but frequencies of major adverse events were similar in the two groups.Tolvaptan initiation within 48 hours of hospitalization for worsening HF in patients manifesting signs and symptoms of volume overload, with long-term continuation of therapy, resulted in neither improvement nor reduction in survival nor in the combined end point of cardiovascular mortality or HF hospitalization, the researchers conclude."The significant benefits on dyspnea, edema, body weight, and serum sodium, coupled with the neutral survival effect, preservation of renal function, and the overall safety profile, define tolvaptan as a potentially useful agent for treating patients with an exacerbation of heart failure", they add."Future investigation is warranted to further define the role of arginine vasopressin receptor blockade in a variety of clinical settings and in patient populations that might be particularly receptive to its clinical benefits," they write. Reference...