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

Abstract

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.

• Authors: Søren L Kristensen, Lars Køber, Pardeep S Jhund, Scott D Solomon, John Kjekshus, Robert S McKelvie, Michael R Zile, Christopher B Granger, John Wikstrand, Michel Komajda, Peter E Carson, Marc A Pfeffer, Karl Swedberg, Hans Wedel, Salim Yusuf, John J V McMurray
• Journal: Circulation (Circulation) Vol. 131 Issue 1 Pg. 43-53 (Jan 06 2015) ISSN: 1524-4539 [Electronic] United States
• PMID: 25406306 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © 2014 American Heart Association, Inc.

Chemical References

• Angiotensin II Type 1 Receptor Blockers
• Benzimidazoles
• Biphenyl Compounds
• Fluorobenzenes
• Hydroxymethylglutaryl-CoA Reductase Inhibitors
• Pyrimidines
• Sulfonamides
• Tetrazoles
• Rosuvastatin Calcium
• Irbesartan
• candesartan

Topics

• Aged
• Aged, 80 and over
• Angiotensin II Type 1 Receptor Blockers (therapeutic use)
• Benzimidazoles (therapeutic use)
• Biphenyl Compounds (therapeutic use)
• Canada (epidemiology)
• Europe (epidemiology)
• Female
• Fluorobenzenes (therapeutic use)
• Geography
• Heart Failure (drug therapy, epidemiology, physiopathology)
• Hospitalization (statistics & numerical data)
• Humans
• Hydroxymethylglutaryl-CoA Reductase Inhibitors (therapeutic use)
• Irbesartan
• Male
• Middle Aged
• Pyrimidines (therapeutic use)
• Risk Factors
• Rosuvastatin Calcium
• Russia (epidemiology)
• Stroke Volume (physiology)
• Sulfonamides (therapeutic use)
• Tetrazoles (therapeutic use)
• Treatment Outcome
• United States (epidemiology)