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Risk of Acute Kidney Injury Among Older Adults With Heart Failure and With Reduced Ejection Fraction Treated With Angiotensin-Neprilysin Inhibitor vs Renin-Angiotensin System Inhibitor in Routine Clinical Care

  • Author Footnotes
    ⁎ Contributed equally as co-first authors.
    ANKEET S. Bhatt
    Footnotes
    ⁎ Contributed equally as co-first authors.
    Affiliations
    Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
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  • Author Footnotes
    ⁎ Contributed equally as co-first authors.
    MUTHIAH Vaduganathan
    Footnotes
    ⁎ Contributed equally as co-first authors.
    Affiliations
    Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
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  • MIN Zhuo
    Affiliations
    Division of Renal Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts

    Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
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  • EDOUARD L. Fu
    Affiliations
    Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
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  • SCOTT D. Solomon
    Affiliations
    Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
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  • Author Footnotes
    ⁎ Contributed equally as co-first authors.
    RISHI J. Desai
    Correspondence
    Reprint requests: Rishi J Desai, PhD, Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, 1620 Tremont Street, Suite 3030-R, Boston, MA 02120. Tel: + 1: 617 278 0932; Fax: + 1 617 232 8602.
    Footnotes
    ⁎ Contributed equally as co-first authors.
    Affiliations
    Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
    Search for articles by this author
  • Author Footnotes
    ⁎ Contributed equally as co-first authors.
Published:September 30, 2022DOI:https://doi.org/10.1016/j.cardfail.2022.09.004

      ABSTRACT

      Background

      The acute hemodynamic effects of sacubitril/valsartan, an angiotensin receptor neprilysin inhibitor (ARNI), may result in early changes in kidney function, raising concerns about acute kidney injury (AKI), particularly in those who are naïve to renin-angiotensin system inhibitors (RASis).

      Methods

      We conducted a cohort study using U.S. Medicare fee-for-service claims data (2014–2017). Patients with HFrEF ≥ 65 years newly initiating ARNI or RASi, with no prior use of either drug class, were included. The primary outcome was hospitalization due to AKI as the primary discharge diagnosis, and the secondary outcome included AKI as a primary or secondary discharge diagnosis. AKI risks were described under an as-treated follow-up approach, with censoring on treatment discontinuation, switch, insurance disenrollment, death, or administrative censoring as well as an intent-to-treat approach. Propensity-score–based fine-stratification weighting was used to account for potential confounding by 81 pre-exposure characteristics. Cumulative incidence functions were used to report absolute risks, and Cox proportional hazards models were used to provide hazard ratios (HR) and 95% confidence intervals (CI).

      Results

      We included 27,166 patients with a mean (SD) age of 73 (7.3) years, and 4155 (15.3%) were initiating ARNI. After propensity score weighting, the 180-day cumulative incidence was 2.7% (2.4%–3.1%) among RASi initiators and 2.7% (2.2%–3.5%) among ARNI initiators for the primary outcome, and it was 6.5% (6.0%–7.1%) and 6.1% (5.2%–7.1%), respectively, for the secondary outcome under as-treated follow-up. HR (95% CI) comparing ARNI with RASi were 0.91 (95% CI: 0.72–1.16) for the primary outcome and 0.92 (95% CI: 0.79–1.08) for the secondary outcome. Similar results were observed in the intent-to-treat analysis.

      Conclusions

      Among a large cohort of U.S. Medicare beneficiaries with HFrEF, ARNI treatment was not associated with higher rates of AKI than RASi treatment. These results provide reassurance for providers considering ARNI initiation in older patients who are RASi-naïve.

      Graphical Abstract

      Key Words

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