Letter by Lother et al Regarding Article, “Finerenone and Cardiovascular Outcomes in Patients With Chronic Kidney Disease and Type 2 Diabetes”

HomeCirculationVol. 144, No. 11Letter by Lother et al Regarding Article, "Finerenone and Cardiovascular Outcomes in Patients With Chronic Kidney Disease and Type 2 Diabetes" Free AccessLetterPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyRedditDiggEmail Jump toFree AccessLetterPDF/EPUBLetter by Lother et al Regarding Article, "Finerenone and Cardiovascular Outcomes in Patients With Chronic Kidney Disease and Type 2 Diabetes" Achim Lother, MD, Christoph Bode, MD and Lutz Hein, MD Achim LotherAchim Lother https://orcid.org/0000-0001-9107-5558 Heart Center Freiburg University, Department of Cardiology and Angiology I (A.L., C.B.), Faculty of Medicine, University of Freiburg, Germany. Institute of Experimental and Clinical Pharmacology and Toxicology (A.L., L.H.), Faculty of Medicine, University of Freiburg, Germany. , Christoph BodeChristoph Bode Heart Center Freiburg University, Department of Cardiology and Angiology I (A.L., C.B.), Faculty of Medicine, University of Freiburg, Germany. and Lutz HeinLutz Hein https://orcid.org/0000-0003-1297-0007 Institute of Experimental and Clinical Pharmacology and Toxicology (A.L., L.H.), Faculty of Medicine, University of Freiburg, Germany. Originally published13 Sep 2021https://doi.org/10.1161/CIRCULATIONAHA.121.053660Circulation. 2021;144:e201To the Editor:The FIDELIO-DKD trial (Finerenone in Reducing Kidney Failure and Disease Progression in Diabetic Kidney Disease) demonstrates that treatment with the new mineralocorticoid receptor antagonist finerenone reduces the incidence of cardiovascular events in patients with diabetic kidney disease.1,2 It is important to note that this was evident in patients both with and without preexisting cardiovascular disease,1 which confirms the central importance of mineralocorticoid receptor in the translation of cardiovascular risk factors into disease.3Use of the presently available steroidal mineralocorticoid receptor antagonists, spironolactone or eplerenone, is associated with an increased risk of hyperkalemia that argued against its use in patients with chronic kidney disease. Finerenone is a newly developed nonsteroidal dihydropyridine mineralocorticoid receptor antagonist, and there were hopes that it might solve this problem.4 In the FIDELIO-DKD trial, the incidence of hyperkalemia >5.5 mmol/L or hyperkalemia leading to discontinuation of the study drug was 21.7 or 2.3% in patients receiving finerenone and 9.8 or 0.9% in the placebo group.2 The authors point out that this is a significant advance compared with dual renin-angiotensin system blockade combining an angiotensin-converting enzyme inhibitor with a renin inhibitor or an angiotensin receptor blocker.2 However, the relative risk was increased 2.2- and 2.6-fold, respectively, by finerenone compared with placebo,2 which is in a similar range as observed for eplerenone or spironolactone versus placebo in addition to renin-angiotensin system blockade.5The moderate absolute incidence of hyperkalemia in FIDELIO-DKD, in both the finerenone and placebo groups, could be explained by the 4- to 16-week run-in period during which patients were selected who tolerated an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker without developing hyperkalemia.1,2 Accordingly, a large proportion of patients in FIDELIO-DKD, 71.4% and 67.8%, respectively, could receive an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker at medium to maximum recommended dose. However, of the 13 911 patients initially enrolled, only 5734 patients were randomly assigned after the run-in period.2 Thus, it seems questionable whether the results can be transferred to clinical practice.In conclusion, although the effect on cardiovascular outcomes appears promising, the improvement with finerenone with respect to hyperkalemia may be overestimated.AcknowledgmentsThe authors are members of SFB1425, funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) – Project #422681845.Disclosures Dr Lother received fees for lectures and serving on advisory boards from Bayer. The other authors report no conflicts.Footnoteshttps://www.ahajournals.org/journal/circReferences1. Filippatos G, Anker SD, Agarwal R, Pitt B, Ruilope LM, Rossing P, Kolkhof P, Schloemer P, Tornus I, Joseph A, et al.; FIDELIO-DKD Investigators. Finerenone and cardiovascular outcomes in patients with chronic kidney disease and type 2 diabetes.Circulation. 2021; 143:540–552. doi: 10.1161/CIRCULATIONAHA.120.051898LinkGoogle Scholar2. Bakris GL, Agarwal R, Anker SD, Pitt B, Ruilope LM, Rossing P, Kolkhof P, Nowack C, Schloemer P, Joseph A, et al.; FIDELIO-DKD Investigators. Effect of finerenone on chronic kidney disease outcomes in type 2 diabetes.N Engl J Med. 2020; 383:2219–2229. doi: 10.1056/NEJMoa2025845CrossrefMedlineGoogle Scholar3. Lother A, Hein L. Vascular mineralocorticoid receptors: linking risk factors, hypertension, and heart disease.Hypertension. 2016; 68:6–10. doi: 10.1161/HYPERTENSIONAHA.116.07418LinkGoogle Scholar4. Pitt B, Kober L, Ponikowski P, Gheorghiade M, Filippatos G, Krum H, Nowack C, Kolkhof P, Kim SY, Zannad F. Safety and tolerability of the novel non-steroidal mineralocorticoid receptor antagonist BAY 94-8862 in patients with chronic heart failure and mild or moderate chronic kidney disease: a randomized, double-blind trial.Eur Heart J. 2013; 34:2453–2463. doi: 10.1093/eurheartj/eht187CrossrefMedlineGoogle Scholar5. Chung EY, Ruospo M, Natale P, Bolignano D, Navaneethan SD, Palmer SC, Strippoli GF. Aldosterone antagonists in addition to renin angiotensin system antagonists for preventing the progression of chronic kidney disease.Cochrane Database Syst Rev. 2020; 10:CD007004. doi: 10.1002/14651858.CD007004.pub4MedlineGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetails September 14, 2021Vol 144, Issue 11Article InformationMetrics Download: 229 © 2021 American Heart Association, Inc.https://doi.org/10.1161/CIRCULATIONAHA.121.053660PMID: 34516302 Originally publishedSeptember 13, 2021 PDF download SubjectsBlood PressureMeta Analysis