Continental differences in clinical characteristics, management, and outcomes in patients hospitalized with worsening heart failure results from the EVEREST (Efficacy of Vasopressin Antagonism in Heart Failure: Outcome Study with Tolvaptan) program.
OBJECTIVE
Our aim was to examine continental and regional differences in baseline characteristics and post-discharge clinical outcomes in the EVEREST (Efficacy of Vasopressin Antagonism in Heart Failure: Outcome Study with Tolvaptan) trial.


BACKGROUND
Continental and regional differences in clinical trials of acute heart failure syndromes (AHFS) have not been well studied.


METHODS
We analyzed data from the EVEREST trial, which randomized 4,133 patients hospitalized for worsening (HF) and left ventricular ejection fraction < or =40% to oral tolvaptan, a vasopressin antagonist, or placebo and followed for a median of 9.9 months. Baseline characteristics, mortality, and outcomes were analyzed across North America (n = 1,251), South America (n = 688), Western Europe (564 patients), and Eastern Europe (n = 1,619).


RESULTS
There were major differences between the 4 groups in the severity, etiology, and management of HF. Unadjusted 1-year mortality and cardiovascular mortality/HF hospitalization were 30.4% and 52.5% in North America, 27.2% and 41.6% in South America, 27.1% and 47.3% in Western Europe, and 20.5% and 35.3% in Eastern Europe. After adjustment, South American patients had the highest overall mortality (hazard ratio: 1.42, 95% confidence interval: 1.15 to 1.76), while Eastern European patients had the lowest cardiovascular death and HF hospitalization rate (hazard ratio: 0.84, 95% confidence interval: 0.73 to 0.97), compared with patients in North America.


CONCLUSIONS
Major continental and regional differences in HF severity, etiology, and management exist among AHFS patients, resulting in varied post-discharge outcomes, despite pre-defined selection criteria. These differences should be taken into account when planning global trials in AHFS. (Efficacy of Vasopressin Antagonism in Heart Failure: Outcome Study with Tolvaptan [EVEREST]; NCT00071331).
Blair
John E A
JE
Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611, USA.
Zannad
Faiez
F
Konstam
Marvin A
MA
Cook
Thomas
T
Traver
Brian
B
Burnett
John C
JC
Grinfeld
Liliana
L
Krasa
Holly
H
Maggioni
Aldo P
AP
Orlandi
Cesare
C
Swedberg
Karl
K
Udelson
James E
JE
Zimmer
Christopher
C
Gheorghiade
Mihai
M
D000368:Aged; D000369:Aged, 80 and over; D001552:Benzazepines / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D006333:Heart Failure / Q000188:drug therapy* / Q000208:ethnology / Q000401:mortality / Q000601:surgery; D006760:Hospitalization; D006801:Humans; D038622:Internationality; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009204:Myocardial Revascularization; D010138:Pacemaker, Artificial / Q000706:statistics & numerical data; D011446:Prospective Studies; D000077602:Tolvaptan; D014667:Vasopressins / Q000037:antagonists & inhibitors*
D001552:Benzazepines; D014667:Vasopressins; D000077602:Tolvaptan