Real-World Experience of Angiotensin Receptor-Neprilysin Inhibition in Reduced Ejection Fraction Heart Failure Patients With Advanced Kidney Disease

Hung-Yu Chang; Chun-Cheng Lin; Chieh-Ju Chao; Yi-Cheng Lin; Yao-Chang Wang; Chia-Te Liao; Jin-Long Huang; Ying-Hsiang Lee; Chun-Yao Huang; Li-Nien Chien; Chien-Yi Hsu

doi:10.1016/j.mayocp.2022.06.007

Real-World Experience of Angiotensin Receptor-Neprilysin Inhibition in Reduced Ejection Fraction Heart Failure Patients With Advanced Kidney Disease

Mayo Clin Proc. 2023 Jan;98(1):88-99. doi: 10.1016/j.mayocp.2022.06.007. Epub 2022 Sep 13.

Authors

Hung-Yu Chang¹, Chun-Cheng Lin², Chieh-Ju Chao³, Yi-Cheng Lin⁴, Yao-Chang Wang⁵, Chia-Te Liao⁶, Jin-Long Huang⁷, Ying-Hsiang Lee⁸, Chun-Yao Huang⁹, Li-Nien Chien¹⁰, Chien-Yi Hsu¹¹

Affiliations

¹ Heart Center, Cheng Hsin General Hospital, Taipei, Taiwan; Faculty of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.
² Department of Electrical Engineering, National Chin-Yi University of Technology, Taichung, Taiwan.
³ Department of Cardiovascular Diseases, Mayo Clinic Rochester, Rochester, Minnesota, USA.
⁴ Department of Pharmacy, Taipei Medical University Hospital, Taipei, Taiwan; School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei, Taiwan.
⁵ Heart Center, Cheng Hsin General Hospital, Taipei, Taiwan; Institute of Emergency and Critical Care Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.
⁶ Division of Cardiology, Chi-Mei Medical Center, Tainan, Taiwan.
⁷ Faculty of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan; Cardiovascular Center, Department of Internal Medicine and Medical Education, Taichung Veterans General Hospital, Taichung, Taiwan; Post-Baccalaureate Medicine of National Chung Hsing University, Taichung, Taiwan.
⁸ Department of Medicine, MacKay Medical College, New Taipei, Taiwan; Department of Artificial Intelligence and Medical Application, MacKay Junior College of Medicine, Nursing, and Management, Taipei, Taiwan; Cardiovascular Center, MacKay Memorial Hospital, Taipei, Taiwan.
⁹ Division of Cardiology and Cardiovascular Research Center, Department of Internal Medicine, Taipei Medical University Hospital, Taipei, Taiwan; Division of Cardiology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; Taipei Heart Institute, Taipei Medical University, Taipei, Taiwan.
¹⁰ Graduate Institution of Data Science, College of Management, Taipei Medical University, Taipei, Taiwan; School of Health Care Administration, College of Management, Taipei Medical University, Taipei, Taiwan; Health Data Analytics and Statistics Center, Office of Data Science, Taipei Medical University, Taipei, Taiwan.
¹¹ Division of Cardiology and Cardiovascular Research Center, Department of Internal Medicine, Taipei Medical University Hospital, Taipei, Taiwan; Division of Cardiology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; Taipei Heart Institute, Taipei Medical University, Taipei, Taiwan. Electronic address: chienyihsu@tmu.edu.tw.

PMID: 36109207
DOI: 10.1016/j.mayocp.2022.06.007

Abstract

Objective: To investigate the effectiveness and safety of angiotensin receptor-neprilysin inhibitors (ARNIs) in real-world patients with heart failure with reduced ejection fraction (HFrEF) and advanced chronic kidney disease (estimated glomerular filtration rate [eGFR] < 30 mL/min per 1.73 m²), which have been excluded from the landmark trials.

Patients and methods: This study examined 3281 patients pooled from two multicenter HFrEF cohorts, and 661 patients with baseline eGFR less than 30 mL/min per 1.73 m² were further analyzed (the Taiwan Society of Cardiology - Heart Failure with reduced Ejection Fraction (TSOC-HFrEF) registry: May 1, 2013 to October 31, 2014, and the Treatment with Angiotensin Receptor neprilysin inhibitor fOr Taiwan Heart Failure patients (TAROT-HF) study: March 1, 2017, to December 31, 2018). Propensity score matching was performed to adjust for confounders. At 1-year follow-up, all-cause mortality, total heart failure hospitalizations, renal function, and left ventricular ejection fraction (LVEF) were used as the endpoints.

Results: After propensity score matching, 510 patients (age, 69.8±13.9 years; male, 61.0%; mean LVEF, 29.8±7.3%; mean eGFR, 19.8±9.0 mL/min per 1.73 m²) were included in the final analysis, including 278 patients receiving ARNI treatment (ARNI group) and 232 patients not on ARNI treatment (non-ARNI group). Baseline characteristics were comparable between the two groups. At 1 year, eGFR and LVEF measurements were significantly higher in the ARNI group than in the non-ARNI group (25.0±17.1 mL/min per 1.73 m² vs 21.4±17.5 mL/min per 1.73 m²; P=.04; and 40.1±12.9% vs. 33.1±10.8%, P<.001, respectively). The ARNI group had significantly lower risks of 1-year all-cause mortality (19.4 vs 30.9 per 100-person year; P=.02), and total HF rehospitalizations (70.0 vs 110.4 per 100-person year; P=.01) than non-ARNI users.

Conclusion: Our results show the effectiveness of ARNIs in HFrEF patients with advanced chronic kidney disease in a real-world setting.

Publication types

Multicenter Study
Research Support, Non-U.S. Gov't

MeSH terms

Aged
Aged, 80 and over
Angiotensin Receptor Antagonists / therapeutic use
Angiotensins
Drug Combinations
Female
Heart Failure* / drug therapy
Humans
Kidney / physiology
Male
Middle Aged
Neprilysin
Receptors, Angiotensin
Renal Insufficiency, Chronic* / complications
Renal Insufficiency, Chronic* / drug therapy
Stroke Volume / physiology
Treatment Outcome
Valsartan
Ventricular Function, Left

Substances

Angiotensin Receptor Antagonists
Angiotensins
Drug Combinations
Neprilysin
Receptors, Angiotensin
Valsartan