International geographic variation in event rates in trials of heart failure with preserved and reduced ejection fraction.


Journal Article

BACKGROUND: International geographic differences in outcomes may exist for clinical trials of heart failure and reduced ejection fraction (HF-REF), but there are few data for those with preserved ejection fraction (HF-PEF). METHODS AND RESULTS: We analyzed outcomes by international geographic region in the Irbesartan in Heart Failure with Preserved systolic function trial (I-Preserve), the Candesartan in Heart failure Assessment of Reduction in Mortality and morbidity (CHARM)-Preserved trial, the CHARM-Alternative and CHARM-Added HF-REF trials, and the Controlled Rosuvastatin Multinational Trial in HF-REF (CORONA). Crude rates of heart failure hospitalization varied by geographic region, and more so for HF-PEF than for HF-REF. Rates in patients with HF-PEF were highest in the United States/Canada (HF hospitalization rate 7.6 per 100 patient-years in I-Preserve; 8.8 in CHARM-Preserved), intermediate in Western Europe (4.8/100 and 4.7/100), and lowest in Eastern Europe/Russia (3.3/100 and 2.8/100). The difference between the United States/Canada versus Eastern Europe/Russia persisted after adjustment for key prognostic variables: adjusted hazard ratios 1.34 (95% confidence interval, 1.01-1.74; P=0.04) in I-Preserve and 1.85 (95% confidence interval, 1.17-2.91; P=0.01) in CHARM-Preserved. In HF-REF, rates of HF hospitalization were slightly lower in Western Europe compared with other regions. For both HF-REF and HF-PEF, there were few regional differences in rates of all-cause or cardiovascular mortality. CONCLUSIONS: The differences in event rates observed suggest there is international geographic variation in 1 or more of the definition and diagnosis of HF-PEF, the risk profile of patients enrolled, and the threshold for hospitalization, which has implications for the conduct of future global trials.

Full Text

Duke Authors

Cited Authors

  • Kristensen, SL; Køber, L; Jhund, PS; Solomon, SD; Kjekshus, J; McKelvie, RS; Zile, MR; Granger, CB; Wikstrand, J; Komajda, M; Carson, PE; Pfeffer, MA; Swedberg, K; Wedel, H; Yusuf, S; McMurray, JJV

Published Date

  • January 6, 2015

Published In

Volume / Issue

  • 131 / 1

Start / End Page

  • 43 - 53

PubMed ID

  • 25406306

Pubmed Central ID

  • 25406306

Electronic International Standard Serial Number (EISSN)

  • 1524-4539

Digital Object Identifier (DOI)

  • 10.1161/CIRCULATIONAHA.114.012284


  • eng

Conference Location

  • United States