title: Effects of tolvaptan on physician-assessed symptoms and signs in patients hospitalized with acute heart failure syndromes: analysis from the efficacy of vasopressin antagonism in heart failure outcome study with tolvaptan (EVEREST) trials.
abstract: BACKGROUND
  A rapid and sustained relief of heart failure (HF) symptoms and signs is an important goal of management in patients hospitalized for acute HF syndromes (AHFS). To date, no novel therapy in AHFS have been shown to improve signs and symptoms throughout hospitalization. This study explores the clinical effects of tolvaptan, a vasopressin-2-receptor antagonist, in addition to standard medical therapies on physician-assessed signs and symptoms in hospitalized AHFS patients.
  
  
  METHODS
  The EVEREST trial randomized 4,133 patients admitted with worsening HF and reduced ejection fraction (≤ 40%) within 48 hours after hospital admission. On each inpatient day, investigators assessed dyspnea, orthopnea, fatigue, jugular venous distension (JVD), rales, and pedal edema by predefined ordinal scales. Responder analyses were performed for each sign and symptom, with significant clinical response defined as a change in one point on the measurement scale.
  
  
  RESULTS
  Post hoc analysis demonstrated greater likelihood of clinical improvement in physician-assessed dyspnea, edema, orthopnea, and JVD among tolvaptan-treated subjects (P < .05) as early as inpatient day 1. This difference was observed throughout hospitalization only for JVD and orthopnea through day 3.
  
  
  CONCLUSIONS
  The addition of tolvaptan to standard therapy for AHFS improves physician-assessed signs and symptoms during hospitalization without serious adverse short- or long-term effects.
authors.affiliation: Department of Emergency Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
authors.forename: Peter S
authors.initials: PS
authors.lastname: Pang
authors.forename: Mihai
authors.initials: M
authors.lastname: Gheorghiade
authors.forename: Jamil
authors.initials: J
authors.lastname: Dihu
authors.forename: Karl
authors.initials: K
authors.lastname: Swedberg
authors.forename: Sadiya
authors.initials: S
authors.lastname: Khan
authors.forename: Aldo P
authors.initials: AP
authors.lastname: Maggioni
authors.forename: Liliana
authors.initials: L
authors.lastname: Grinfeld
authors.forename: Faiez
authors.initials: F
authors.lastname: Zannad
authors.forename: John C
authors.initials: JC
authors.lastname: Burnett
authors.forename: John
authors.initials: J
authors.lastname: Ouyang
authors.forename: James E
authors.initials: JE
authors.lastname: Udelson
authors.forename: Marvin A
authors.initials: MA
authors.lastname: Konstam
mesh_terms: D000368:Aged; D065092:Antidiuretic Hormone Receptor Antagonists; D001552:Benzazepines / Q000627:therapeutic use*; D005260:Female; D006333:Heart Failure / Q000175:diagnosis / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D000077602:Tolvaptan
chemical_list: D065092:Antidiuretic Hormone Receptor Antagonists; D001552:Benzazepines; D000077602:Tolvaptan