Effects of tolvaptan on dyspnoea relief from the EVEREST trials.
OBJECTIVE
To 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.


RESULTS
Post 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.


CONCLUSIONS
Post 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.
Pang
Peter S
PS
Department of Emergency Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
Konstam
Marvin A
MA
Krasa
Holly B
HB
Swedberg
Karl
K
Zannad
Faiez
F
Blair
John E A
JE
Zimmer
Christopher
C
Teerlink
John R
JR
Maggioni
Aldo P
AP
Burnett
John C
JC
Grinfeld
Liliana
L
Ouyang
John
J
Udelson
James E
JE
Gheorghiade
Mihai
M
D000368:Aged; D001552:Benzazepines / Q000008:administration & dosage*; D004311:Double-Blind Method; D004417:Dyspnea / Q000188:drug therapy*; D005260:Female; D006801:Humans; D008297:Male; D001261:Pulmonary Atelectasis / Q000209:etiology; D019141:Respiratory System Agents / Q000008:administration & dosage*; D000077602:Tolvaptan; D016896:Treatment Outcome
D001552:Benzazepines; D019141:Respiratory System Agents; D000077602:Tolvaptan