Kidney and cardiovascular effects of canagliflozin according to age and sex: a post hoc analysis of the CREDENCE randomized clinical trial

Yi, T.W.; Smyth, B.; Tanna, G.L. di; Arnott, C.; Cardoza, K.; Kang, A.; ... ; CREDENCE Trial Investigators (2023)

Article / Letter to editor

Rationale & Objective: It is unclear whether the effect of canagliflozin on adverse kidney and cardiovascular events in those with diabetic kid-ney disease varies by age and sex. We assessed the effects of canagliflozin among age group categories and between sexes in the Canagli-flozin and Renal Endpoints in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE) study.Study Design: Secondary analysis of a random-ized controlled trial. Setting & Participants: Participants in the CREDENCE trial. Intervention: Participants were randomly assigned to receive canagliflozin 100 mg/d or placebo.Outcomes: Primary composite outcome of kid-ney failure, doubling of serum creatinine con-centration, or death due to kidney or cardiovascular disease. Prespecified secondary and safety outcomes were also analyzed. Out-comes were evaluated by age at baseline (<60, 60-69, and >_70 years) and sex in the intention-to-treat population using Cox regression models.Results: The mean age of the cohort was 63.0 & PLUSMN; 9.2 years, and 34% were female. Older age and female sex were independently associ-ated with a lower risk of the composite of adverse kidney outcomes. There was no evidence that the effect of canagliflozin on the primary outcome (acomposite 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 [0.4 8-0.82], and 0.89 [0.61-1.29] for ages <60, 60-69, and >_70 years, respectively; P = 0.3 for interaction) or sexes (HRs, 0.71 [95% CI, 0.5 4-0.95] and 0.69 [0.56-0.8 4] in women and men, respectively; P = 0.8 for interaction). No differences in safety outcomes by age group or sex were observed.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.

• All authors: Yi, T.W.; Smyth, B.; Tanna, G.L. di; Arnott, C.; Cardoza, K.; Kang, A.; Pollock, C.; Agarwal, R.; Bakris, G.; Charytan, D.M.; Zeeuw, D. de; Heerspink, H.J.L.; Neal, B.; Wheeler, D.C.; Cannon, C.P.; Zhang, H.; Zinman, B.; Perkovic, V.; Levin, A.; Mahaffey, K.W.; Jardine, M.; CREDENCE Trial Investigators
• Date: 2023-06-21
• Journal: American Journal of Kidney Diseases
• Volume: 82
• Issue: 1
• Pages: 84 - 96.e1
• DOI: doi:10.1053/j.ajkd.2022.12.015
• Link: https://www.sciencedirect.com/science/article/pii/S0272638623005371?via%...