Agarwal, Rajiv L.Anker, Stefan D.Filippatos, Gerasimos S.Pitt, BertramRossing, PeterRuilope Urioste, Luis MiguelBoletis, JohnToto, RobertUmpierrez, Guillermo E.FIDELIO-DKDEt al.2022-01-152022-01-152022Agarwal, R., Anker, S. D., Filippatos, G., Pitt, B., Rossing, P., Ruilope, L. M., Boletis, J., Toto, R., Umpierrez, G. E., Wanner, C., Wada, T., Scott, C., Joseph, A., Ogbaa, I., Roberts, L., Scheerer, M. F., & Bakris, G. L. (2022). Effects of canagliflozin versus finerenone on cardiorenal outcomes: exploratory post hoc analyses from FIDELIO-DKD compared to reported CREDENCE results. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association, 37(7), 1261–1269. https://doi.org/10.1093/ndt/gfab3360931-05091460-2385http://hdl.handle.net/11268/10567Background The 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. Methods Patients 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. 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 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). 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.engAttribution-NonCommercial 4.0 Internacionalhttp://creativecommons.org/licenses/by-nc/4.0/Diabetes mellitus tipo 2Fallo renal crónicoDiuréticosjournal article10.1093/ndt/gfab336open accessSistema endocrinoEnfermedad cardiovascularTratamiento médico