Effects of tolvaptan on dyspnoea relief from the EVEREST trials

Peter S. Pang, Marvin A. Konstam, Holly B. Krasa, Karl Swedberg, Faiez Zannad, John E.A. Blair, Christopher Zimmer, John R. Teerlink, Aldo P. Maggioni, John C. Burnett, Liliana Grinfeld, John Ouyang, James E. Udelson, Mihai Gheorghiade

Research output: Contribution to journalArticlepeer-review

59 Scopus citations


AimsTo describe the effects of tolvaptan therapy on dyspnoea relief based on timing of delivery, influence of concomitant therapies, and baseline patient and clinical characteristics. Also, the influence of clinical trial design on dyspnoea measurement, from the Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study with Tolvaptan (EVEREST) trials.Methods and resultsPost hoc analysis was performed based on the endpoint of patient-assessed dyspnoea. Changes from baseline at inpatient Day 1 were compared between treatment groups by the van Elteren test. Pre-determined subgroup analyses were also performed. Tolvaptan's effects are greatest within 12 h after first dose with an additional, but modest dyspnoea improvement benefit irrespective of time after admission. Overall, patients continue to report dyspnoea improvement up to 60 h after admission. The window of enrolment, up to 48 h after admission, combined with measurement on 'Day 1' led to a wide range over when dyspnoea was assessed.ConclusionPost hoc analysis suggests that tolvaptan modestly improves dyspnoea compared with standard therapy alone, regardless if given early or relatively late after hospitalization, and also across major pre-specified subgroups, despite ongoing background therapy aimed at relieving signs and symptoms. Significant variability around when dyspnoea was assessed, in addition to the persistence of dyspnoea despite ongoing background therapy, may influence how future clinical trials assess dyspnoea in acute heart failure syndromes.

Original languageEnglish (US)
Pages (from-to)2233-2240
Number of pages8
JournalEuropean heart journal
Issue number18
StatePublished - Sep 2009


  • Acute heart failure syndromes
  • Clinical trials
  • Dyspnoea
  • Heart failure
  • Vasopressin antagonists

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine


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