Kidney and Cardiovascular Effects of Canagliflozin According to Age and Sex: A Post Hoc Analysis of the CREDENCE Randomized Clinical Trial

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 E...

Full description

Saved in:

Bibliographic Details
Published in:	American journal of kidney diseases Vol. 82; no. 1; pp. 84 - 96.e1
Main Authors:	Zhang, Hong, Heerspink, Hiddo J.L., Neal, Bruce, Pollock, Carol, Charytan, David M., Berli, Mario Alberto, Coloma, Gabriela Cecilia, Colombo, Hugo, Gelersztein, Elizabeth, Krynski, Fernando, Sessa, Horacio, Valdez, Maria, Droste, Carolyn, Nicholls, Kathy, Proietto, Joseph, Turatti, Luiz Alberto Andreotti, Borges, João Lindolfo Cunha, Vêncio, Sérgio Alberto Cunha, d’Avila, Domingos, Sabbag, Ângela Regina Nazario, Shinkov, Alexander, Temelkova, Margarita, Montenegro, María Alicia Fernández, Gajardo, Victor Saavedra, Chen, Qinkai, Gan, Shenglian, Kong, Yaozhong, Wang, Guixia, Alexandra Terront Lozano, Monica, Haase, Franklin Paul, Ramirez Roca, Luis Alberto, Csiky, Botond, Kiss, Krisztian, Zsom, Marianna, Abraham, Oomman, Peringat, Jayameena, Sreedhar, Reddy, Ceriello, Antonio, Piatti, Piermarco, Sasso, Ferdinando Carlo, Sakakibara, Terue, Takai, Masahiko, Kozloviene, Dalia, Abdul Ghani, Rohana, Kadir, Khalid Abdul, Ng, Kee Sing, Cruz, Juan Baas, Wong, Alfredo Chew, Escalante, Tonatiu Diaz, Baron, Paul Frenk, Luna Ceballos, Rosa Isela, Vera, Gregorio Obrador, Castellanos, Ricardo Orozco, Pattzi, Hiromi Rodriguez, Chavez, Eloisa Tellez, Noonan, Paul, Watson, Edward, Young, Simon, Yap, Yvette Ethel, Kaminska, Anna, Dobronravov, Vladimir, Samoylova, Yulia, Vorobyev, Sergey, Prozesky, Hans, Seeber, Mary, Park, Sun-Hee, Torres, Manuel Muñoz, Vera, Merce Perez, Gonzalez, Alfonso Soto, Sheu, Wayne H-H, Golovchenko, Oleksandr, Kazmirchuk, Anatoliy, Komisarenko, Iuliia, Korzh, Oleksii, Tryshchuk, Nadiya, English, Patrick, Jackson, Alan, Philip, Sam, Turner, Wayne, Abdallah, Joseph, Barnhill, Peggy, Barranco, Elizabeth, El-Shahawy, Mohamed, Galphin, Claude, Gorson, David, Gulati, Rakesh, Hartman, Israel, Hon, George, Khitan, Zeid, Kim, Sun, Maheshwari, Hiralal, Nassar, Tareq, Nossuli, A. Kaldun, Pettis, Karlton, Phillips, Andrea, Sekkarie, Mohamed, Surampudi, Prasanth, Sussman, Sherry, Varghese, Freemu, Welsh, Jean
Format:	Journal Article
Language:	English
Published:	United States Elsevier Inc 01-07-2023
Subjects:	age canagliflozin cardiovascular outcomes chronic kidney disease diabetes Diabetic kidney disease kidney outcomes sex sodium/glucose cotransporter 2 inhibitors sodium/glucose cotransporter 2 inhibitors kidney outcomes chronic kidney disease cardiovascular outcomes canagliflozin sex diabetes age Diabetic kidney disease
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	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. Secondary analysis of a randomized controlled trial. Participants in the CREDENCE trial. Participants were randomly assigned to receive canagliflozin 100mg/d or placebo. 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. 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. This was a post hoc analysis with multiple comparisons. 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. 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. The original CREDENCE trial was registered at ClinicalTrials.gov with study number NCT02065791. [Display omitted]
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 ObjectType-Undefined-3
ISSN:	0272-6386 1523-6838
DOI:	10.1053/j.ajkd.2022.12.015