Rationale and design of the multicenter, randomized, double-blind, placebo-controlled study to evaluate the efficacy of vasopressin antagonism in heart failure: Outcome study with Tolvaptan (EVEREST)

Mihai Gheorghiade, Cesare Orlandi, John C. Burnett, David Demets, Liliana Grinfeld, Aldo Maggioni, Karl Swedberg, James E. Udelson, Faiez Zannad, Christopher Zimmer, Marvin A. Konstam*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

155 Scopus citations

Abstract

Background: Hospitalizations for worsening heart failure due to fluid overload (congestion) are common. Agents that treat congestion without causing electrolyte abnormalities or worsening renal function are needed. Tolvaptan is an oral vasopressin (V2) antagonist that decreases body weight and increases urine volume without inducing renal dysfunction or hypokalemia. The Efficacy of Vasopressin antagonism in Heart Failure Outcome Study with Tolvaptan (EVEREST) trial is evaluating mortality, morbidity, and patient-assessed global clinical status in patients treated with tolvaptan compared with standard care. Methods and Results: Patients are eligible for inclusion if they have a reduced left ventricular ejection fraction and are hospitalized for worsening heart failure with evidence of systemic congestion. Patients are randomized 1:1 to tolvaptan 30 mg/day or matching placebo for a minimum of 60 days. Time to all-cause mortality and time to cardiovascular mortality or heart failure hospitalization are the coprimary end points. Patient-assessed global clinical status and quality of life are also evaluated. EVEREST will be continued until 1065 deaths occur. As of April 18, 2005, 2260 patients have been enrolled. Conclusion: Tolvaptan has been shown to reduce body weight in patients with worsening heart failure without inducing renal dysfunction or causing hypokalemia. The results of EVEREST will determine whether these effects translate into improved clinical outcomes.

Original languageEnglish (US)
Pages (from-to)260-269
Number of pages10
JournalJournal of Cardiac Failure
Volume11
Issue number4
DOIs
StatePublished - May 1 2005

Keywords

  • Clinical trials
  • Heart failure
  • Morbidity
  • Mortality
  • Vasopressin

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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