Kidney and Cardiovascular Effects of Canagliflozin According to Age and Sex: A Post Hoc Analysis of the CREDENCE Randomized Clinical Trial.
Publication/Presentation Date
7-1-2023
Abstract
RATIONALE & OBJECTIVE: It is unclear whether the effect of canagliflozin on adverse kidney and cardiovascular events in those with diabetic kidney disease varies by age and sex. We assessed the effects of canagliflozin among age group categories and between sexes in the Canagliflozin and Renal Endpoints in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE) study.
STUDY DESIGN: Secondary analysis of a randomized controlled trial.
SETTING & PARTICIPANTS: Participants in the CREDENCE trial.
INTERVENTION: Participants were randomly assigned to receive canagliflozin 100mg/d or placebo.
OUTCOMES: Primary composite outcome of kidney failure, doubling of serum creatinine concentration, or death due to kidney or cardiovascular disease. Prespecified secondary and safety outcomes were also analyzed. Outcomes were evaluated by age at baseline (
RESULTS: The mean age of the cohort was 63.0±9.2 years, and 34% were female. Older age and female sex were independently associated with a lower risk of the composite of adverse kidney outcomes. There was no evidence that the effect of canagliflozin on the primary outcome (a composite of kidney failure, a doubling of serum creatinine concentration, or death from kidney or cardiovascular causes) differed between age groups (HRs, 0.67 [95% CI, 0.52-0.87], 0.63 [0.48-0.82], and 0.89 [0.61-1.29] for ages
LIMITATIONS: This was a post hoc analysis with multiple comparisons.
CONCLUSIONS: Canagliflozin consistently reduced the relative risk of kidney events in people with diabetic kidney disease in both sexes and across age subgroups. As a result of greater background risk, the absolute reduction in adverse kidney outcomes was greater in younger participants.
FUNDING: This post hoc analysis of the CREDENCE trial was not funded. The CREDENCE study was sponsored by Janssen Research and Development and was conducted collaboratively by the sponsor, an academic-led steering committee, and an academic research organization, George Clinical.
TRIAL REGISTRATION: The original CREDENCE trial was registered at ClinicalTrials.gov with study number NCT02065791.
Volume
82
Issue
1
First Page
84
Last Page
96
ISSN
1523-6838
Published In/Presented At
Yi, T. W., Smyth, B., Di Tanna, G. L., Arnott, C., Cardoza, K., Kang, A., Pollock, C., Agarwal, R., Bakris, G., Charytan, D. M., de Zeeuw, D., Heerspink, H. J. L., Neal, B., Wheeler, D. C., Cannon, C. P., Zhang, H., Zinman, B., Perkovic, V., Levin, A., Mahaffey, K. W., … CREDENCE Trial Investigators (2023). Kidney and Cardiovascular Effects of Canagliflozin According to Age and Sex: A Post Hoc Analysis of the CREDENCE Randomized Clinical Trial. American journal of kidney diseases : the official journal of the National Kidney Foundation, 82(1), 84–96.e1. https://doi.org/10.1053/j.ajkd.2022.12.015
Disciplines
Medicine and Health Sciences
PubMedID
36889425
Department(s)
Department of Medicine
Document Type
Article