{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T06:13:21Z","timestamp":1789020801357,"version":"build-2803163510"},"reference-count":14,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2021,11,25]],"date-time":"2021-11-25T00:00:00Z","timestamp":1637798400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Chameleon Communications International"},{"DOI":"10.13039\/100004326","name":"Bayer AG","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004326","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,6,23]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>The nonsteroidal mineralocorticoid receptor antagonist finerenone and the sodium\u2013glucose 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\u201327] relative risk reduction; in CREDENCE, the primary endpoint had a 30% (95% CI 18\u201341) 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\u00a0\u226540% from baseline. In contrast, the primary endpoint in the CREDENCE trial included a sustained decline in eGFR of\u00a0\u226557% from baseline and cardiovascular (CV) death. This post hoc exploratory analysis investigated how differences in trial design\u2014inclusion\/exclusion criteria and definition of primary outcomes\u2014influenced observed treatment effects.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Patients from FIDELIO-DKD who met the CKD inclusion criteria of the CREDENCE study (urine albumin: creatinine ratio\u00a0&amp;gt;300\u20135000\u00a0mg\/g\u00a0and an eGFR of 30\u2013&amp;lt;90\u00a0mL\/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\u00a0\u226557% sustained for\u00a0\u22654 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>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <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\u20130.87)]. 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\u20130.82)].<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <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>\n               <\/jats:sec>","DOI":"10.1093\/ndt\/gfab336","type":"journal-article","created":{"date-parts":[[2021,11,22]],"date-time":"2021-11-22T20:11:39Z","timestamp":1637611899000},"page":"1261-1269","source":"Crossref","is-referenced-by-count":56,"title":["Effects of canagliflozin versus finerenone on cardiorenal outcomes: exploratory <i>post hoc<\/i> analyses from FIDELIO-DKD compared to reported CREDENCE results"],"prefix":"10.1093","volume":"37","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8355-7100","authenticated-orcid":false,"given":"Rajiv","family":"Agarwal","sequence":"first","affiliation":[{"name":"Richard L. 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