International differences in clinical characteristics, management, and outcomes in acute heart failure patients: better short-term outcomes in patients enrolled in Eastern Europe and Russia in the PROTECT trial.
OBJECTIVE
The implications of geographical variation are unknown following adjustment for hospital length of stay (LOS) in heart failure (HF) trials that included patients whether or not they had systolic dysfunction. We investigated regional differences in an international acute HF trial.


RESULTS
The PROTECT trial investigated 2033 patients with acute HF and renal dysfunction hospitalized at 173 sites in 17 countries with randomization to rolofylline or placebo. We grouped enrolling countries into six regions. Baseline characteristics, in-hospital management, and outcomes were explored by region. The primary study outcome was 60-day mortality or cardiovascular/renal hospitalization. Secondary outcomes included 180-day mortality. Of 2033 patients, 33% were from Eastern Europe, 19% from Western Europe, 16% from Israel, 15% from North America, 14% from Russia, and 3% from Argentina. Marked differences in baseline characteristics, HF phenotype, in-hospital diuretic and vasodilator strategies, and LOS were observed by region. LOS was shortest in North America and Israel (median 5 days) and longest in Russia (median 15 days). Regional event rates varied significantly. Following multivariable adjustment, region was an independent predictor of the risk of mortality/hospitalization at 60 days, with the lowest risk in Russia (hazard ratio 0.39, 95% confidence interval 0.23-0.64 vs. Western Europe) due to lower rehospitalization; mortality differences were attenuated by 180 days.


CONCLUSIONS
In an international HF trial, there were differences in baseline characteristics, treatments, LOS, and rehospitalization amongst regions, but little difference in longer term mortality. Rehospitalization differences exist independent of LOS. This analysis may help inform future trial design and should be externally validated.
Duke University, Durham, NC, USA.
Robert J
RJ
Mentz
Gad
G
Cotter
John G F
JG
Cleland
Susanna R
SR
Stevens
Karen
K
Chiswell
Beth A
BA
Davison
John R
JR
Teerlink
Marco
M
Metra
Adriaan A
AA
Voors
Liliana
L
Grinfeld
Mikhail
M
Ruda
Viacheslav
V
Mareev
Chaim
C
Lotan
Daniel M
DM
Bloomfield
Mona
M
Fiuzat
Michael M
MM
Givertz
Piotr
P
Ponikowski
Barry M
BM
Massie
Christopher M
CM
O'Connor
D000208:Acute Disease; D058916:Adenosine A1 Receptor Antagonists / Q000627:therapeutic use; D000368:Aged; D000369:Aged, 80 and over; D004232:Diuretics / Q000009:adverse effects / Q000627:therapeutic use*; D005061:Europe, Eastern; D005260:Female; D005843:Geography; D006333:Heart Failure / Q000188:drug therapy* / Q000401:mortality; D006760:Hospitalization / Q000706:statistics & numerical data*; D006801:Humans; D038622:Internationality; D007902:Length of Stay / Q000706:statistics & numerical data*; D008297:Male; D008875:Middle Aged; D011788:Quality of Life; D012426:Russia; D014970:Xanthines / Q000009:adverse effects / Q000627:therapeutic use*
D058916:Adenosine A1 Receptor Antagonists; D004232:Diuretics; D014970:Xanthines; C073525:rolofylline
Acute heart failure; Global variation; Length of stay; Outcomes; Regional differences; Trial