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