AIMS: 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. METHODS AND RESULTS: The PROTECT trial investigated 2033 patients with acute HF and renal dysfunctionhospitalized at 173 sites in 17 countries with randomization torolofylline 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.
RCT Entities:
AIMS: 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. METHODS AND 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.
Authors: Seth W Glickman; John G McHutchison; Eric D Peterson; Charles B Cairns; Robert A Harrington; Robert M Califf; Kevin A Schulman Journal: N Engl J Med Date: 2009-02-19 Impact factor: 91.245
Authors: Robb D Kociol; Li Liang; Adrian F Hernandez; Lesley H Curtis; Paul A Heidenreich; Clyde W Yancy; Gregg C Fonarow; Eric D Peterson Journal: Am Heart J Date: 2013-04-06 Impact factor: 4.749
Authors: Christopher M O'Connor; Mona Fiuzat; Karl Swedberg; Michael Caron; Bruce Koch; Peter E Carson; Wendy Gattis-Stough; Gordon W Davis; Michael R Bristow Journal: J Am Coll Cardiol Date: 2011-08-23 Impact factor: 24.094
Authors: R M Califf; K F Adams; W J McKenna; M Gheorghiade; B F Uretsky; S E McNulty; H Darius; K Schulman; F Zannad; E Handberg-Thurmond; F E Harrell; W Wheeler; J Soler-Soler; K Swedberg Journal: Am Heart J Date: 1997-07 Impact factor: 4.749
Authors: Mihai Gheorghiade; Kanan Patel; Gerasimos Filippatos; Stefan D Anker; Dirk J van Veldhuisen; John G F Cleland; Marco Metra; Inmaculada B Aban; Stephen J Greene; Kirkwood F Adams; John J V McMurray; Ali Ahmed Journal: Eur J Heart Fail Date: 2013-01-25 Impact factor: 15.534
Authors: M Komajda; F Follath; K Swedberg; J Cleland; J C Aguilar; A Cohen-Solal; R Dietz; A Gavazzi; W H Van Gilst; R Hobbs; J Korewicki; H C Madeira; V S Moiseyev; I Preda; J Widimsky; N Freemantle; J Eastaugh; J Mason Journal: Eur Heart J Date: 2003-03 Impact factor: 29.983
Authors: J G F Cleland; K Swedberg; F Follath; M Komajda; A Cohen-Solal; J C Aguilar; R Dietz; A Gavazzi; R Hobbs; J Korewicki; H C Madeira; V S Moiseyev; I Preda; W H van Gilst; J Widimsky; N Freemantle; Joanne Eastaugh; J Mason Journal: Eur Heart J Date: 2003-03 Impact factor: 29.983
Authors: Jacob P Kelly; Robert J Mentz; Vic Hasselblad; Justin A Ezekowitz; Paul W Armstrong; Faiez Zannad; G Michael Felker; Robert M Califf; Christopher M O'Connor; Adrian F Hernandez Journal: Am Heart J Date: 2015-04-15 Impact factor: 4.749
Authors: Robert J Mentz; Lothar Roessig; Barry H Greenberg; Naoki Sato; Kaori Shinagawa; Daniel Yeo; Bernard W K Kwok; Eugenio B Reyes; Henry Krum; Burkert Pieske; Stephen J Greene; Andrew P Ambrosy; Jacob P Kelly; Faiez Zannad; Bertram Pitt; Carolyn S P Lam Journal: JACC Heart Fail Date: 2016-06 Impact factor: 12.035
Authors: Stephen J Greene; Adrian F Hernandez; Jie-Lena Sun; Javed Butler; Paul W Armstrong; Justin A Ezekowitz; Faiez Zannad; João Pedro Ferreira; Adrian Coles; Marco Metra; Adriaan A Voors; Robert M Califf; Christopher M O'Connor; Robert J Mentz Journal: Circ Cardiovasc Qual Outcomes Date: 2018-10
Authors: Robert J Mentz; Eric J Velazquez; Marco Metra; Colleen McKendry; Karen Chiswell; Mona Fiuzat; Michael M Givertz; Adriaan A Voors; John R Teerlink; Christopher M O'Connor Journal: Future Cardiol Date: 2015-09-25
Authors: Robert J Mentz; Vic Hasselblad; Adam D DeVore; Marco Metra; Adriaan A Voors; Paul W Armstrong; Justin A Ezekowitz; W H Wilson Tang; Phillip J Schulte; Kevin J Anstrom; Adrian F Hernandez; Eric J Velazquez; Christopher M O'Connor Journal: Am J Cardiol Date: 2015-11-18 Impact factor: 2.778