Finerenone and Cardiovascular Outcomes in Patients With Chronic Kidney Disease and Type 2 Diabetes
Author Block: Gerasimos Filippatos, Natl and Kapodistrian Univ of Athens, Athens, Greece; Stefan D Anker, German Ctr for Cardiovascular Res Partner Site Berlin, Charité Univsmedizin, Berlin, Germany; Rajiv Agarwal, Indiana Univ, Indianapolis, IN; Bertram Pitt, Univ of Michigan Sch of Med, Ann Arbor, MI; Peter Rossing, Steno Diabetes Ctr Copenhagen & Univ of Copenhagen, Copenhagen, Denmark; Luis M Ruilope, Inst of Res imas12, Hosp 12 de Octubre & European Univ of Madrid, Madrid, Spain; Peter Kolkhof, Patrick Schloemer, Ingo Tornus, Amer Joseph, Bayer AG, Berlin, Germany; George L Bakris, Univ of Chicago Med, Chicago, IL
Disclosure Block: G.Filippatos: Research Grant; Significant; Bayer, Vifor, Medtronic, Boehringer Ingelheim, Novartis, Sanofi. A.Joseph: Employment; Significant; Bayer AG. G.L.Bakris: Honoraria; Modest; Merck, Novo Nordisk, Relypsa, Astra-Zeneca. S.D.Anker: Honoraria; Modest; Bayer, Boehringer Ingelheim, Honoraria; Significant; Vifor, Research Grant; Significant; Abbott Vascular, Vifor. R.Agarwal: Other; Modest; American Journal of Nephrology, Nephrology Dialysis and Transplantation , UpToDate, Other; Significant; Akebia, Bayer, Johnson & Johnson, Boehringer Ingelheim, Takeda, Daiichi Sankyo, Amgen, AstraZeneca, Sanofi, Celgene, Reata, Relypsa, GlaxoSmithKline, Gilead, ER Squibb and Sons, Fresenius, Ironwood Ph, Research Grant; Modest; GlaxoSmithKline. B.Pitt: Other; Significant; Bayer, Astra Zeneca, Sanofi/Lexicon, KBP Pharmaceuticals, Relypsa/Vifor. P.Rossing: Other; Modest; Bayer, Astellas, Astra Zeneca, Boehringer ingelheim, Novo Nordisk, Gilead, Mundipharma, Merck, Vifor, Sanofi. L.M.Ruilope: Honoraria; Modest; Daiichi-Sankyo, Novartis, Sanofi, Research Grant; Significant; Astra Zeneca, Speaker/Speaker's Bureau; Modest; Medtronic, Speaker/Speaker's Bureau; Significant; Bayer. P.Kolkhof: Employment; Significant; BAYER AG. P.Schloemer: Employment; Significant; Bayer AG. I.Tornus: Employment; Significant; Bayer AG, Stock Shareholder; Modest; Bayer AG.
Introduction: Patients with chronic kidney disease (CKD) and type 2 diabetes (T2D) face substantial cardiovascular (CV) morbidity and mortality. Finerenone, a novel, nonsteroidal, selective, mineralocorticoid receptor antagonist (MRA), reduced the primary composite endpoint related to kidney failure outcomes in the FIDELIO-DKD trial. The effect of finerenone on overall CV outcomes, and specific CV outcomes in patients with and without prior history of CV disease (CVD) is the subject of this report. Methods: FIDELIO-DKD was a randomized, double-blind, placebo-controlled, multicenter phase III clinical trial. Patients with urine albumin-to-creatinine ratio (UACR) ≥30-<300 mg/g and eGFR ≥25-<60 mL/min/1.73 m2, with a history of diabetic retinopathy or UACR ≥300-≤5000 mg/g and eGFR ≥25-<75 mL/min/1.73 m2 were included. Patients were randomized 1:1 to receive either oral finerenone (at titrated doses of 10 mg or 20 mg once daily) or placebo. Prespecified CV outcomes included a composite endpoint of CV death, non-fatal myocardial infarction, non-fatal stroke, or hospitalization for heart failure. In a prespecified subgroup analysis, outcomes were analyzed by the presence or absence of a history of atherosclerotic CVD at baseline, defined as investigator-reported medical history of coronary artery disease, myocardial infarction, peripheral arterial disease, ischaemic stroke or carotid endarterectomy. Results: A total of 5,734 patients from 913 sites in 48 countries were randomized. Of the 5,674 patients eligible for analysis, 2,605 (45.9%) had a history of CVD at baseline. Over a median follow-up of 2.6 years, finerenone lowered the risk of the composite CV outcome compared with placebo (hazard ratio [HR], 0.86; 95% confidence interval [CI], 0.75-0.99; P=0.034); with CV benefit observed irrespective of history of CVD (HR, 0.85; 95% CI, 0.71-1.02 in patients with a history of CVD; HR, 0.86; 95% CI, 0.68-1.08 in patients without a history of CVD; P-value for interaction, 0.85). Overall adverse events were similar between finerenone and placebo, with a low incidence of hyperkalemia-related treatment discontinuation (2.3% and 0.9% in the finerenone and placebo groups, respectively). Conclusion: In the FIDELIO-DKD trial, finerenone reduced the risk of the composite CV outcome in patients with CKD and T2D compared with placebo. These benefits were consistent in both patients with and without a history of CVD. (Funded by Bayer AG; FIDELIO-DKD clinicaltrials.gov number NCT02540993)