Effects of Oral Tolvaptan in Patients Hospitalized for Worsening Heart Failure: The EVEREST Outcome Trial

• Published in: JAMA : the journal of the American Medical Association 2007-03, Vol.297 (12), p.1319-1331
• Main Authors: Konstam, Marvin A, Gheorghiade, Mihai, Burnett, John C, Grinfeld, Liliana, Maggioni, Aldo P, Swedberg, Karl, Udelson, James E, Zannad, Faiez, Cook, Thomas, Ouyang, John, Zimmer, Christopher, Orlandi, Cesare, Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study With Tolvaptan (EVEREST) Investigators, for the
• Format: Article
• Language: English
• Subjects: Administration; Administration, Oral; Aged; Antagonist drugs; Antidiuretic Hormone Receptor Antagonists; Benzazepines - therapeutic use; Biological and medical sciences; Blood Urea Nitrogen; Body Weight - drug effects; Cardiac and Cardiovascular Systems; Cardiology. Vascular system; Cardiovascular Agents - therapeutic use; Clinical outcomes; Clinical trials; Congestive/blood/drug therapy/mortality; Creatinine - blood; Double-Blind Method; Drug therapy; Female; General aspects; Heart; Heart Failure; Heart Failure - blood; Heart Failure - drug therapy; Heart Failure - mortality; Heart failure, cardiogenic pulmonary edema, cardiac enlargement; Hospitalization; Humans; Kaplan-Meier Estimate; Kaplan-Meiers Estimate; Kardiologi; Male; Medical sciences; Middle Aged; Mortality; Oral; Quality of Life; Receptors; Sodium - blood; Vasopressin/antagonists & inhibitors
• ISSN: 0098-7484; 1538-3598; 1538-3598
• DOI: 10.1001/jama.297.12.1319

CONTEXT Vasopressin mediates fluid retention in heart failure. Tolvaptan, a vasopressin V2 receptor blocker, shows promise for management of heart failure. OBJECTIVE To investigate the effects of tolvaptan initiated in patients hospitalized with heart failure. DESIGN, SETTING, AND PARTICIPANTS The Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study With Tolvaptan (EVEREST), an event-driven, randomized, double-blind, placebo-controlled study. The outcome trial comprised 4133 patients within 2 short-term clinical status studies, who were hospitalized with heart failure, randomized at 359 North American, South American, and European sites between October 7, 2003, and February 3, 2006, and followed up during long-term treatment. INTERVENTION 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. MAIN OUTCOME MEASURES Dual primary end points were all-cause mortality (superiority and noninferiority) and cardiovascular death or hospitalization for heart failure (superiority only). Secondary end points included changes in dyspnea, body weight, and edema. RESULTS 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 upper confidence limit for the mortality difference was within the prespecified noninferiority margin of 1.25 (P