Effects of canagliflozin versus finerenone on cardiorenal outcomes: exploratory post hoc analyses from FIDELIO-DKD compared to reported CREDENCE results.

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  • Additional Information
    • Source:
      Publisher: Oxford University Press Country of Publication: England NLM ID: 8706402 Publication Model: Print Cited Medium: Internet ISSN: 1460-2385 (Electronic) Linking ISSN: 09310509 NLM ISO Abbreviation: Nephrol Dial Transplant Subsets: MEDLINE
    • Publication Information:
      Publication: Oxford : Oxford University Press
      Original Publication: [Berlin ; New York, NY] : Springer International, [c1986-
    • Subject Terms:
      Cardiovascular Diseases*/drug therapy ; Cardiovascular Diseases*/etiology ; Cardiovascular Diseases*/prevention & control ; Diabetes Mellitus, Type 2*/complications ; Diabetes Mellitus, Type 2*/drug therapy ; Diabetic Nephropathies* ; Heart Failure*/drug therapy ; Renal Insufficiency, Chronic*/chemically induced ; Renal Insufficiency, Chronic*/complications ; Renal Insufficiency, Chronic*/drug therapy ; Sodium-Glucose Transporter 2 Inhibitors*/therapeutic use; Canagliflozin/therapeutic use ; Humans ; Naphthyridines
    • Abstract:
      Background: The nonsteroidal mineralocorticoid receptor antagonist finerenone and the sodium-glucose cotransporter-2 inhibitor (SGLT-2i) canagliflozin reduce cardiorenal risk in albuminuric patients with chronic kidney disease (CKD) and type 2 diabetes (T2D). At first glance, the results of Finerenone in Reducing Kidney Failure and Disease Progression in Diabetic Kidney Disease (FIDELIO-DKD) (ClinicalTrials.gov, NCT02540993) and Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE) appear disparate. In FIDELIO-DKD, the primary endpoint had an 18% [95% confidence interval (CI) 7-27] relative risk reduction; in CREDENCE, the primary endpoint had a 30% (95% CI 18-41) relative risk reduction. Unlike CREDENCE, the FIDELIO-DKD trial included patients with high albuminuria but excluded patients with symptomatic heart failure with reduced ejection fraction. The primary endpoint in the FIDELIO-DKD trial was kidney specific and included a sustained decline in the estimated glomerular filtration rate (eGFR) of ≥40% from baseline. In contrast, the primary endpoint in the CREDENCE trial included a sustained decline in eGFR of ≥57% from baseline and cardiovascular (CV) death. This post hoc exploratory analysis investigated how differences in trial design-inclusion/exclusion criteria and definition of primary outcomes-influenced observed treatment effects.
      Methods: Patients from FIDELIO-DKD who met the CKD inclusion criteria of the CREDENCE study (urine albumin: creatinine ratio >300-5000 mg/g and an eGFR of 30-<90 mL/min/1.73 m2 at screening) were included in this analysis. The primary endpoint was a cardiorenal composite (CV death, kidney failure, eGFR decrease of ≥57% sustained for ≥4 weeks or renal death). Patients with symptomatic heart failure with reduced ejection fraction were excluded from FIDELIO-DKD. Therefore, in a sensitivity analysis, we further adjusted for the baseline prevalence of heart failure.
      Results: Of 4619/5674 (81.4%) patients who met the subgroup inclusion criteria, 49.6% were treated with finerenone and 50.4% received placebo. The rate of the cardiorenal composite endpoint was 43.9/1000 patient-years with finerenone compared with 59.5/1000 patient-years with placebo. The relative risk was significantly reduced by 26% with finerenone versus placebo [hazard ratio (HR) 0.74 (95% CI 0.63-0.87)]. In CREDENCE, the rate of the cardiorenal composite endpoint was 43.2/1000 patient-years with canagliflozin compared with 61.2/1000 patient-years with placebo; a 30% risk reduction was observed with canagliflozin [HR 0.70 (95% CI 0.59-0.82)].
      Conclusions: This analysis highlights the pitfalls of direct comparisons between trials. When key differences in trial design are considered, FIDELIO-DKD and CREDENCE demonstrate cardiorenal benefits of a similar magnitude.
      (© The Author(s) 2021. Published by Oxford University Press on behalf of the ERA.)
    • Comments:
      Comment in: Nephrol Dial Transplant. 2022 Feb 25;:. (PMID: 35212745)
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    • Contributed Indexing:
      Keywords: CREDENCE; FIDELIO-DKD; canagliflozin; cardiorenal; finerenone
    • Molecular Sequence:
      ClinicalTrials.gov NCT02540993
    • Accession Number:
      0 (Naphthyridines)
      0 (Sodium-Glucose Transporter 2 Inhibitors)
      0 (finerenone)
      0SAC974Z85 (Canagliflozin)
    • Publication Date:
      Date Created: 20211201 Date Completed: 20220624 Latest Revision: 20220721
    • Publication Date:
      20221213
    • Accession Number:
      PMC9217637
    • Accession Number:
      10.1093/ndt/gfab336
    • Accession Number:
      34850173