• Rajiv Agarwal, Stefan D Anker, Gerasimos Filippatos, Bertram Pitt, Peter Rossing, Luis M Ruilope, John Boletis, Robert Toto, Guillermo E Umpierrez, Christoph Wanner, Takashi Wada, Charlie Scott, Amer Joseph, Ike Ogbaa, Luke Roberts, Markus F Scheerer, and George L Bakris.
• Richard L. Roudebush VA Medical Center and Indiana University, Indianapolis, Indiana, USA.
• Nephrol. Dial. Transplant. 2021 Nov 25.

BackgroundThe nonsteroidal mineralocorticoid receptor antagonist finerenone and the sodium-glucose co-transporter-2 inhibitor canagliflozin reduce cardiorenal risk in albuminuric patients with chronic kidney disease (CKD) and type 2 diabetes (T2D). At first glance, the results of FIDELIO-DKD (ClinicalTrials.gov, NCT02540993) and CREDENCE appear disparate. In FIDELIO-DKD, the primary end-point had a 18% (95% CI 7% to 27%) relative risk reduction; in CREDENCE the primary end-point had a 30% (95% CI 18% to 41%) relative risk reduction. Unlike CREDENCE, FIDELIO-DKD trial included patients with high albuminuria but excluded patients with symptomatic heart failure with reduced ejection fraction. The primary end-point in the FIDELIO-DKD trial was kidney specific and included a sustained decline in eGFR of ≥40% from baseline. In contrast, the primary end-point in the CREDENCE trial was included a sustained decline in eGFR of ≥57% from baseline and cardiovascular death. This post-hoc exploratory analysis investigated how differences in trial design-inclusion/exclusion criteria and definition of primary outcomes- influenced observed treatment effects.MethodsPatients from FIDELIO-DKD who met the CKD inclusion criteria of the CREDENCE study (urine albumin-to-creatinine ratio >300-5000 mg/g and an estimated glomerular filtration rate of 30-<90 ml/min/1.73 m2 at screening) were included in this analysis. The primary end point was a cardiorenal composite (cardiovascular death, kidney failure, estimated glomerular filtration rate 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.ResultsOf 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 end point was 43.9/1000 patient years with finerenone compared to 59.5/1000 patient years with placebo. The relative risk was significantly reduced by 26% with finerenone versus placebo (hazard ratio 0.74, 95% CI 0.63-0.87).In CREDENCE, the rate of the cardiorenal composite end point was 43.2/1000 patient years with canagliflozin compared to 61.2/1000 patient years with placebo; a 30% risk reduction was observed with canagliflozin (hazard ratio 0.70, 95% CI 0.59-0.82).ConclusionsThis 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.© The Author(s) 2021. Published by Oxford University Press on behalf of the ERA.

3 keywords...

hide…