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

Media type: E-Article
Title: Effects of canagliflozin versus finerenone on cardiorenal outcomes: exploratory post hoc analyses from FIDELIO-DKD compared to reported CREDENCE results
Contributor: Agarwal, Rajiv; Anker, Stefan D; Filippatos, Gerasimos; Pitt, Bertram; Rossing, Peter; Ruilope, Luis M; Boletis, John; Toto, Robert; Umpierrez, Guillermo E; Wanner, Christoph; Wada, Takashi; Scott, Charlie; Joseph, Amer; Ogbaa, Ike; Roberts, Luke; Scheerer, Markus F; Bakris, George L
imprint: Oxford University Press (OUP), 2022
Published in: Nephrology Dialysis Transplantation
Language: English
DOI: 10.1093/ndt/gfab336
ISSN: 0931-0509; 1460-2385
Origination:
Footnote:
Description: <jats:title>ABSTRACT</jats:title> <jats:sec> <jats:title>Background</jats:title> <jats:p>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.</jats:p> </jats:sec> <jats:sec> <jats:title>Methods</jats:title> <jats:p>Patients from FIDELIO-DKD who met the CKD inclusion criteria of the CREDENCE study (urine albumin: creatinine ratio &gt;300–5000 mg/g and an eGFR of 30–&lt;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.</jats:p> </jats:sec> <jats:sec> <jats:title>Results</jats:title> <jats:p>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)].</jats:p> </jats:sec> <jats:sec> <jats:title>Conclusions</jats:title> <jats:p>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.</jats:p> </jats:sec>
Access State: Open Access

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