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

  • Hung-Yu Chang
    Affiliations
    Heart Center, Cheng Hsin General Hospital, Taipei, Taiwan

    Faculty of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
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  • Chun-Cheng Lin
    Affiliations
    Department of Electrical Engineering, National Chin-Yi University of Technology, Taichung, Taiwan
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  • Chieh-Ju Chao
    Affiliations
    Department of Cardiovascular Diseases, Mayo Clinic Rochester, Rochester, Minnesota, USA
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  • Yi-Cheng Lin
    Affiliations
    Department of Pharmacy, Taipei Medical University Hospital, Taipei, Taiwan

    School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei, Taiwan
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  • Yao-Chang Wang
    Affiliations
    Heart Center, Cheng Hsin General Hospital, Taipei, Taiwan

    Institute of Emergency and Critical Care Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
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  • Chia-Te Liao
    Affiliations
    Division of Cardiology, Chi-Mei Medical Center, Tainan, Taiwan
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  • Jin-Long Huang
    Affiliations
    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
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  • Ying-Hsiang Lee
    Affiliations
    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
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  • Chun-Yao Huang
    Affiliations
    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
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  • Li-Nien Chien
    Affiliations
    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
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  • Chien-Yi Hsu
    Correspondence
    Correspondence: Address to Chien-Yi Hsu, MD, PhD, Division of Cardiology and Cardiovascular Research Center, Department of Internal Medicine, Taipei Medical University Hospital, No. 252, Wuxing St., 110 Xinyi, Taipei, Taiwan.
    Affiliations
    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
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Published:September 12, 2022DOI:https://doi.org/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.

      Abbreviations and Acronyms:

      ARNI (angiotensin receptor-neprilysin inhibitor), CKD (chronic renal disease), eGFR (estimated glomerular filtration rate), HF (heart failure), HFrEF (heart failure with reduced ejection fraction), LVEF (left ventricular ejection fraction)
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