{"doi":"10.1093/ndt/gfab336","title":"Effects of canagliflozin versus finerenone on cardiorenal outcomes: exploratory <i>post hoc</i> analyses from FIDELIO-DKD compared to reported CREDENCE results","abstract":"BACKGROUND: 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.","journal":"Nephrology Dialysis Transplantation","year":2021,"id":154758,"datarank":1.72283668227296,"base_score":4.143134726391533,"endowment":4.143134726391533,"self_citation_contribution":0.62147020895873,"citation_network_contribution":1.10136647331423,"self_endowment_contribution":0.62147020895873,"citer_contribution":1.10136647331423,"corpus_percentile":null,"corpus_rank":null,"citation_count":62,"citer_count":47,"citers_with_citation_signal":32,"citers_with_endowment":32,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.956,"is_data_producer":true,"deposit_databanks":{"ClinicalTrials.gov":["NCT02540993"]},"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":228545,"name":"Stefan D. Anker","orcid":"0000-0002-0805-8683","position":1,"is_corresponding":false},{"id":58220,"name":"Gerasimos Filippatos","orcid":"0000-0002-5640-0332","position":2,"is_corresponding":false},{"id":98761,"name":"Bertram Pitt","orcid":"0000-0001-5880-275X","position":3,"is_corresponding":false},{"id":42050,"name":"Peter Rossing","orcid":"0000-0002-1531-4294","position":4,"is_corresponding":false},{"id":40690,"name":"Luís M. Ruilope","orcid":"0000-0001-6278-7951","position":5,"is_corresponding":false},{"id":54899,"name":"John Boletis","orcid":"0000-0001-8202-2892","position":6,"is_corresponding":false},{"id":273078,"name":"Robert Toto","orcid":null,"position":7,"is_corresponding":false},{"id":228523,"name":"Guillermo E. Umpierrez","orcid":"0000-0002-3252-5026","position":8,"is_corresponding":false},{"id":74376,"name":"Christoph Wanner","orcid":"0000-0001-9507-5301","position":9,"is_corresponding":false},{"id":655466,"name":"Takashi Wada","orcid":"0000-0002-0123-3645","position":10,"is_corresponding":false},{"id":626303,"name":"Charlie Scott","orcid":"0000-0002-2816-4889","position":11,"is_corresponding":false},{"id":273072,"name":"Amer Joseph","orcid":null,"position":12,"is_corresponding":false},{"id":656188,"name":"Ike Ogbaa","orcid":null,"position":13,"is_corresponding":false},{"id":655467,"name":"Luke Roberts","orcid":"0000-0002-9910-4648","position":14,"is_corresponding":false},{"id":627274,"name":"Markus F. Scheerer","orcid":null,"position":15,"is_corresponding":false},{"id":6,"name":"George L. Bakris","orcid":"0000-0003-1183-1267","position":16,"is_corresponding":false},{"id":255772,"name":"Rajiv Agarwal","orcid":"0000-0001-8355-7100","position":0,"is_corresponding":true}],"reference_count":14,"raw_metadata":null,"created_at":"2026-07-18T23:43:54.469024Z","pmid":"34850173","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}