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

dc.contributor.authorAgarwal, Rajiv
dc.contributor.authorAnker, Stefan D.
dc.contributor.authorFilippatos, Gerasimos
dc.contributor.authorPitt, Bertram
dc.contributor.authorRossing, Peter
dc.contributor.authorRuilope, Luis M.
dc.contributor.authorBoletis, John
dc.contributor.authorToto, Robert
dc.contributor.authorUmpierrez, Guillermo E.
dc.contributor.authorWanner, Christoph
dc.contributor.authorWada, Takashi
dc.contributor.authorScott, Charlie
dc.contributor.authorJoseph, Amer
dc.contributor.authorOgbaa, Ike
dc.contributor.authorRoberts, Luke
dc.contributor.authorScheerer, Markus F.
dc.contributor.authorBakris, George L.
dc.contributor.authorFIDELIO-DKD investigators
dc.contributor.departmentMedicine, School of Medicine
dc.date.accessioned2024-05-01T15:18:53Z
dc.date.available2024-05-01T15:18:53Z
dc.date.issued2022
dc.description.abstractBackground: 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.
dc.eprint.versionFinal published version
dc.identifier.citationAgarwal R, Anker SD, Filippatos G, et al. Effects of canagliflozin versus finerenone on cardiorenal outcomes: exploratory post hoc analyses from FIDELIO-DKD compared to reported CREDENCE results. Nephrol Dial Transplant. 2022;37(7):1261-1269. doi:10.1093/ndt/gfab336
dc.identifier.urihttps://hdl.handle.net/1805/40405
dc.language.isoen_US
dc.publisherOxford University Press
dc.relation.isversionof10.1093/ndt/gfab336
dc.relation.journalNephrology Dialysis Transplantation
dc.rightsAttribution-NonCommercial 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by-nc/4.0/
dc.sourcePMC
dc.subjectCREDENCE
dc.subjectFIDELIO-DKD
dc.subjectCanagliflozin
dc.subjectCardiorenal
dc.subjectFinerenone
dc.titleEffects of canagliflozin versus finerenone on cardiorenal outcomes: exploratory post hoc analyses from FIDELIO-DKD compared to reported CREDENCE results
dc.typeArticle
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