Kidney and Cardiovascular Effects of Canagliflozin According to Age and Sex : A Post Hoc Analysis of the CREDENCE Randomized Clinical Trial
Copyright © 2023 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved..
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 (<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±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<60, 60-69, and≥70 years, respectively; P=0.3for interaction) or sexes (HRs, 0.71 [95% CI, 0.54-0.95] and 0.69 [0.56-0.84] in women and men, respectively; P=0.8for 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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:82 |
|---|---|
| Enthalten in: |
American journal of kidney diseases : the official journal of the National Kidney Foundation - 82(2023), 1 vom: 01. Juli, Seite 84-96.e1 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Yi, Tae Won [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 26.06.2023 Date Revised 16.11.2023 published: Print-Electronic ClinicalTrials.gov: NCT02065791 Citation Status MEDLINE |
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| doi: |
10.1053/j.ajkd.2022.12.015 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM353951587 |
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| 100 | 1 | |a Yi, Tae Won |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Kidney and Cardiovascular Effects of Canagliflozin According to Age and Sex |b A Post Hoc Analysis of the CREDENCE Randomized Clinical Trial |
| 264 | 1 | |c 2023 | |
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| 500 | |a Date Completed 26.06.2023 | ||
| 500 | |a Date Revised 16.11.2023 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a ClinicalTrials.gov: NCT02065791 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2023 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved. | ||
| 520 | |a 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 | ||
| 520 | |a STUDY DESIGN: Secondary analysis of a randomized controlled trial | ||
| 520 | |a SETTING & PARTICIPANTS: Participants in the CREDENCE trial | ||
| 520 | |a INTERVENTION: Participants were randomly assigned to receive canagliflozin 100mg/d or placebo | ||
| 520 | |a 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 (<60, 60-69, and≥70 years) and sex in the intention-to-treat population using Cox regression models | ||
| 520 | |a 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<60, 60-69, and≥70 years, respectively; P=0.3for interaction) or sexes (HRs, 0.71 [95% CI, 0.54-0.95] and 0.69 [0.56-0.84] in women and men, respectively; P=0.8for interaction). No differences in safety outcomes by age group or sex were observed | ||
| 520 | |a LIMITATIONS: This was a post hoc analysis with multiple comparisons | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a TRIAL REGISTRATION: The original CREDENCE trial was registered at ClinicalTrials.gov with study number NCT02065791 | ||
| 650 | 4 | |a Randomized Controlled Trial | |
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Diabetic kidney disease | |
| 650 | 4 | |a age | |
| 650 | 4 | |a canagliflozin | |
| 650 | 4 | |a cardiovascular outcomes | |
| 650 | 4 | |a chronic kidney disease | |
| 650 | 4 | |a diabetes | |
| 650 | 4 | |a kidney outcomes | |
| 650 | 4 | |a sex | |
| 650 | 4 | |a sodium/glucose cotransporter 2 inhibitors | |
| 650 | 7 | |a Canagliflozin |2 NLM | |
| 650 | 7 | |a 0SAC974Z85 |2 NLM | |
| 650 | 7 | |a Sodium-Glucose Transporter 2 Inhibitors |2 NLM | |
| 650 | 7 | |a Creatinine |2 NLM | |
| 650 | 7 | |a AYI8EX34EU |2 NLM | |
| 700 | 1 | |a Smyth, Brendan |e verfasserin |4 aut | |
| 700 | 1 | |a Di Tanna, Gian Luca |e verfasserin |4 aut | |
| 700 | 1 | |a Arnott, Clare |e verfasserin |4 aut | |
| 700 | 1 | |a Cardoza, Kathryn |e verfasserin |4 aut | |
| 700 | 1 | |a Kang, Amy |e verfasserin |4 aut | |
| 700 | 1 | |a Pollock, Carol |e verfasserin |4 aut | |
| 700 | 1 | |a Agarwal, Rajiv |e verfasserin |4 aut | |
| 700 | 1 | |a Bakris, George |e verfasserin |4 aut | |
| 700 | 1 | |a Charytan, David M |e verfasserin |4 aut | |
| 700 | 1 | |a de Zeeuw, Dick |e verfasserin |4 aut | |
| 700 | 1 | |a Heerspink, Hiddo J L |e verfasserin |4 aut | |
| 700 | 1 | |a Neal, Bruce |e verfasserin |4 aut | |
| 700 | 1 | |a Wheeler, David C |e verfasserin |4 aut | |
| 700 | 1 | |a Cannon, Christopher P |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Hong |e verfasserin |4 aut | |
| 700 | 1 | |a Zinman, Bernard |e verfasserin |4 aut | |
| 700 | 1 | |a Perkovic, Vlado |e verfasserin |4 aut | |
| 700 | 1 | |a Levin, Adeera |e verfasserin |4 aut | |
| 700 | 1 | |a Mahaffey, Kenneth W |e verfasserin |4 aut | |
| 700 | 1 | |a Jardine, Meg |e verfasserin |4 aut | |
| 700 | 0 | |a CREDENCE Trial Investigators |e verfasserin |4 aut | |
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| 700 | 1 | |a Mahaffey, Kenneth W |e investigator |4 oth | |
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| 700 | 1 | |a Bakris, George |e investigator |4 oth | |
| 700 | 1 | |a Brenner, Barry M |e investigator |4 oth | |
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| 700 | 1 | |a Charytan, David M |e investigator |4 oth | |
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| 700 | 1 | |a Greene, Tom |e investigator |4 oth | |
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| 700 | 1 | |a Heerspink, Hiddo J L |e investigator |4 oth | |
| 700 | 1 | |a Levin, Adeera |e investigator |4 oth | |
| 700 | 1 | |a Meininger, Gary |e investigator |4 oth | |
| 700 | 1 | |a Neal, Bruce |e investigator |4 oth | |
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