Efficacy and Safety of Dapagliflozin in Patients With Chronic Kidney Disease Across the Spectrum of Frailty.

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  • Additional Information
    • Source:
      Publisher: published on behalf of the Gerontological Society of America by Oxford University Press Country of Publication: United States NLM ID: 9502837 Publication Model: Print Cited Medium: Internet ISSN: 1758-535X (Electronic) Linking ISSN: 10795006 NLM ISO Abbreviation: J Gerontol A Biol Sci Med Sci Subsets: MEDLINE
    • Publication Information:
      Publication: Washington, DC : published on behalf of the Gerontological Society of America by Oxford University Press
      Original Publication: Washington, DC : Gerontological Society of America, c1995-
    • Subject Terms:
      Diabetes Mellitus, Type 2*/complications ; Diabetes Mellitus, Type 2*/drug therapy ; Frailty*/complications ; Diabetic Nephropathies*/complications ; Diabetic Nephropathies*/drug therapy ; Renal Insufficiency, Chronic*/complications ; Renal Insufficiency, Chronic*/drug therapy ; Kidney Failure, Chronic*/complications ; Benzhydryl Compounds* ; Glucosides*; Humans
    • Abstract:
      Background: A sizeable proportion of patients with chronic kidney disease (CKD) are reported to be frail. Here we examined the safety and efficacy of dapagliflozin in patients with CKD by frailty level.
      Methods: Adults with CKD, with/without type 2 diabetes, with an estimated glomerular filtration rate (eGFR) of 25-75 mL/min/1.73 m2, and urinary albumin-to-creatinine ratio 200-5 000 mg/g were randomized to dapagliflozin (10 mg/day) or placebo. The primary endpoint was a composite of sustained ≥50% eGFR decline, end-stage kidney disease (ESKD), or death from kidney or cardiovascular (CV) causes.
      Results: Frailty index (FI), assessed by Rockwood cumulative deficit approach, was calculable in 4 303/4 304 (99.9%) patients: 1 162 (27.0%) in not-to-mildly frail (FI ≤0.210), 1 642 (38.2%) in moderately frail (FI 0.211-0.310), and 1 499 (34.8%) in severely frail categories (FI >0.311). Dapagliflozin reduced the risk of the primary composite endpoint across all FI categories (hazard ratios [95% confidence interval {CI}]: 0.50 [0.33-0.76], 0.62 [0.45-0.85], and 0.64 [0.49--0.83], respectively; p-interaction = 0.67). Results were similar for secondary outcomes including kidney composite outcome (sustained ≥50% eGFR decline, ESKD or death from kidney cause; p-interaction = 0.44), CV endpoint (heart failure hospitalization or CV death; p-interaction = 0.63), and all-cause mortality (p-interaction p = .42). Results were consistent when using FI as a continuous variable. Occurrence of serious adverse events was numerically lower in patients receiving dapagliflozin versus placebo in all FI categories (16.9% vs 20.1%, 26.3% vs 30.7%, and 42.9% vs 47.8%, in not-to-mildly, moderately, and severely frail categories, respectively).
      Conclusions: The relative benefit of dapagliflozin for all outcomes was consistent across all frailty categories, with no difference in associated safety.
      (© The Author(s) 2023. Published by Oxford University Press on behalf of The Gerontological Society of America.)
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    • Grant Information:
      AstraZeneca
    • Contributed Indexing:
      Keywords: Cardiovascular disease; Diabetes; SGLT-2 inhibitors
    • Accession Number:
      1ULL0QJ8UC (dapagliflozin)
      0 (Benzhydryl Compounds)
      0 (Glucosides)
    • Publication Date:
      Date Created: 20230801 Date Completed: 20240126 Latest Revision: 20240130
    • Publication Date:
      20240130
    • Accession Number:
      PMC10809037
    • Accession Number:
      10.1093/gerona/glad181
    • Accession Number:
      37527836