Global Differences in Heart Failure With Preserved Ejection Fraction: The PARAGON-HF Trial

Jasper Tromp; Brian L Claggett; Jiankang Liu; Alice M Jackson; Pardeep S Jhund; Lars Køber; Jiří Widimský; Sergey A Boytsov; Vijay K Chopra; Inder S Anand; Junbo Ge; Chen-Huan Chen; Aldo P Maggioni; Felipe Martinez; Milton Packer; Marc A Pfeffer; Burkert Pieske; Margaret M Redfield; Jean L Rouleau; Dirk J Van Veldhuisen; Faiez Zannad; Michael R Zile; Adel R Rizkala; Akiko Inubushi-Molessa; Martin P Lefkowitz; Victor C Shi; John J V McMurray; Scott D Solomon; Carolyn S P Lam; PARAGON-HF Investigators

doi:10.1161/CIRCHEARTFAILURE.120.007901

Global Differences in Heart Failure With Preserved Ejection Fraction: The PARAGON-HF Trial

Circ Heart Fail. 2021 Apr;14(4):e007901. doi: 10.1161/CIRCHEARTFAILURE.120.007901. Epub 2021 Apr 19.

Authors

Jasper Tromp^{1

2

3

4}, Brian L Claggett⁵, Jiankang Liu⁵, Alice M Jackson⁶, Pardeep S Jhund⁶, Lars Køber⁷, Jiří Widimský⁸, Sergey A Boytsov⁹, Vijay K Chopra¹⁰, Inder S Anand¹¹, Junbo Ge¹², Chen-Huan Chen¹³, Aldo P Maggioni¹⁴, Felipe Martinez¹⁵, Milton Packer¹⁶, Marc A Pfeffer⁵, Burkert Pieske¹⁷, Margaret M Redfield¹⁸, Jean L Rouleau¹⁹, Dirk J Van Veldhuisen³, Faiez Zannad²⁰, Michael R Zile²¹, Adel R Rizkala²², Akiko Inubushi-Molessa²², Martin P Lefkowitz²², Victor C Shi²², John J V McMurray⁶, Scott D Solomon⁵, Carolyn S P Lam^{1

2

3}; PARAGON-HF Investigators

Affiliations

¹ National Heart Centre Singapore (J.T., C.S.P.L.).
² Duke-NUS Medical School, Singapore (J.T., C.S.P.L.).
³ Department of Cardiology, University Medical Centre Groningen, University of Groningen, the Netherlands (J.T., D.J.V.V., C.S.P.L.).
⁴ Saw Swee Hock School of Public Health, National University of Singapore, Singapore (J.T.).
⁵ Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (B.L.C., J.L., M.A.P., S.D.S.).
⁶ British Heart Foundation Cardiovascular Research Centre, Institute of Cardiovascular and Medical Sciences, University of Glasgow, United Kingdom (A.M.J., P.S.J., J.J.V.M.).
⁷ Department of Cardiology, Heart Centre, Rigshospitalet, Copenhagen University Hospital, Denmark (L.K.).
⁸ First Faculty of Medicine, Charles University Prague, Czech Republic (J.W.).
⁹ National Research Center for Cardiology of the Ministry of Health of the Russian Federation, Moscow (S.B.).
¹⁰ Heart Failure and Research Max Super Specialty Hospital Saket, New Delhi, India (V.C.).
¹¹ Department of Medicine, VA Medical Center and University of Minnesota, Minneapolis (I.S.A.).
¹² Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, China (J.G.).
¹³ Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan, Republic of China (C.-H.C.).
¹⁴ Associazione Nazionale Medici Cardiologi Ospedalieri, Florence, Italy (A.P.M.).
¹⁵ Universidad Nacional of Cordoba, Argentina (F.M.).
¹⁶ Baylor Heart and Vascular Institute, Baylor University Medical Center, Dallas, TX (M.P.).
¹⁷ Department of Internal Medicine, Cardiology Charité, Universitaetsmedizin Berlin, Campus Virchow Klinikum Berlin, Germany (B.P.).
¹⁸ Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN (M.M.R.).
¹⁹ Institut de Cardiologie de Montréal, Université de Montréal, QC, Canada (J.L.R.).
²⁰ Inserm CIC 1433 and Université de Lorraine, Centre Hospitalier Régional Universitaire, Nancy, France (F.Z.).
²¹ Medical University of South Carolina and Ralph H. Johnson Veterans Administration Medical Center, Charleston (M.R.Z.).
²² Novartis Pharmaceuticals Corporation, East Hanover, NJ (A.R.R., A.I.-M., M.P.L., V.C.S.).

PMID: 33866828
DOI: 10.1161/CIRCHEARTFAILURE.120.007901

Abstract

Background: Heart failure with preserved ejection fraction (HFpEF) is a global public health problem with important regional differences. We investigated these differences in the PARAGON-HF trial (Prospective Comparison of Angiotensin Receptor Neprilysin Inhibitor With Angiotensin Receptor Blocker Global Outcomes in HFpEF), the largest and most inclusive global HFpEF trial.

Methods: We studied differences in clinical characteristics, outcomes, and treatment effects of sacubitril/valsartan in 4796 patients with HFpEF from the PARAGON-HF trial, grouped according to geographic region.

Results: Regional differences in patient characteristics and comorbidities were observed: patients from Western Europe were oldest (mean 75±7 years) with the highest prevalence of atrial fibrillation/flutter (36%); Central/Eastern European patients were youngest (mean 71±8 years) with the highest prevalence of coronary artery disease (50%); North American patients had the highest prevalence of obesity (65%) and diabetes (49%); Latin American patients were younger (73±9 years) and had a high prevalence of obesity (53%); and Asia-Pacific patients had a high prevalence of diabetes (44%), despite a low prevalence of obesity (26%). Rates of the primary composite end point of total hospitalizations for HF and death from cardiovascular causes were lower in patients from Central Europe (9 per 100 patient-years) and highest in patients from North America (28 per 100 patient-years), which was primarily driven by a greater number of total hospitalizations for HF. The effect of treatment with sacubitril-valsartan was not modified by region (interaction P>0.05).

Conclusions: Among patients with HFpEF recruited worldwide in PARAGON-HF, there were important regional differences in clinical characteristics and outcomes, which may have implications for the design of future clinical trials. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01920711.

Keywords: atrial fibrillation; coronary artery disease; heart failure; prevalence; risk factors.

Publication types

Randomized Controlled Trial
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Aged
Aminobutyrates / therapeutic use*
Angiotensin Receptor Antagonists / therapeutic use*
Biphenyl Compounds / therapeutic use*
Double-Blind Method
Drug Combinations
Female
Global Health*
Heart Failure / drug therapy*
Heart Failure / mortality*
Heart Failure / physiopathology
Hospitalization / statistics & numerical data
Humans
Male
Neprilysin / therapeutic use*
Quality of Life
Risk Factors
Stroke Volume*
Valsartan / therapeutic use*

Substances

Aminobutyrates
Angiotensin Receptor Antagonists
Biphenyl Compounds
Drug Combinations
Valsartan
Neprilysin
sacubitril and valsartan sodium hydrate drug combination

Associated data

ClinicalTrials.gov/NCT01920711

Abstract

Publication types

MeSH terms

Substances

Associated data

Grants and funding