Finerenone Reduces New-Onset Atrial Fibrillation in Patients With Chronic Kidney Disease and Type 2 Diabetes

JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY

卷:78

Article

Filippatos, Gerasimos¹  Bakris, George L.²  Pitt, Bertram³  Agarwal, Rajiv^4,5  Rossing, Peter^6,7  Ruilope, Luis M.^8,9,10,11  Butler, Javed¹²  Lam, Carolyn S. P.^13,14  Kolkhof, Peter¹⁵  Roberts, Luke¹⁶  Tasto, Christoph¹⁷  Joseph, Amer¹⁸  Anker, Stefan D.¹⁹ 

[1] Natl & Kapodistrian Univ Athens, Attikon Univ Hosp, Sch Med, Dept Cardiol, Athens, Greece

[2] Univ Chicago Med, Dept Med, Chicago, IL USA

[3] Univ Michigan, Sch Med, Dept Med, Ann Arbor, MI 48104 USA

[4] Richard L Roudebush VA Med Ctr, Indianapolis, IN USA

[5] Indiana Univ, Indianapolis, IN 46204 USA

[6] Steno Diabet Ctr Copenhagen, Gentofte, Denmark

[7] Univ Copenhagen, Dept Clin Med, Copenhagen, Denmark

[8] Inst Res Imas12, Cardiorenal Translat Lab, Madrid, Spain

[9] Inst Res Imas12, Hypertens Unit, Madrid, Spain

[10] Hosp Univ 12 Octubre, CIBER CV, Madrid, Spain

[11] European Univ Madrid, Fac Sport Sci, Madrid, Spain

[12] Univ Mississippi, Dept Med, Jackson, MS 39216 USA

[13] Natl Heart Ctr Singapore, Singapore, Singapore

[14] Duke Natl Univ Singapore, Singapore, Singapore

[15] Bayer AG, Preclin Res Cardiovasc, Res & Dev, Wuppertal, Germany

[16] Bayer PLC, Study Med Experts, Reading, Berks, England

[17] Bayer AG, Stat & Data Insights, Res & Dev, Wuppertal, Germany

[18] Bayer AG, Cardiol & Nephrol Clin Dev, Berlin, Germany

[19] Charite, Ctr Regenerat Therapies, German Ctr Cardiovasc Res, Berlin Inst Hlth,Dept Cardiol CVK,Partner Site Be, Berlin, Germany

关键词: chronic kidney disease;    clinical trial;    finerenone;    mineralocorticoid receptor antagonist;    new-onset atrial fibrillation;    type 2 diabetes;   

DOI  :  10.1016/j.jacc.2021.04.079

来源: Elsevier

【 摘 要 】

BACKGROUND Patients with chronic kidney disease (CKD) and type 2 diabetes (T2D) are at risk of atrial fibrillation or flutter (AFF) due to cardiac remodeling and kidney complications. Finerenone, a novel, selective, nonsteroidal mineralocorticoid receptor antagonist, inhibited cardiac remodeling in preclinical models. OBJECTIVES This work aims to examine the effect of finerenone on new-onset AFF and cardiorenal effects by history of AFF in the Finerenone in Reducing Kidney Failure and Disease Progression in Diabetic Kidney Disease (FIDELIO-DKD) study. METHODS Patients with CKD and T2D were randomized (1:1) to finerenone or placebo. Eligible patients had a urine albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g, an estimated glomerular filtration rate (eGFR) >= 25 to <75 ml/min/1.73 m(2) and received optimized doses of renin-angiotensin system blockade. Effect on new-onset AFF was evaluated as a pre-specified outcome adjudicated by an independent cardiologist committee. The primary composite outcome (time to first onset of kidney failure, a sustained decrease of >= 40% in eGFR from baseline, or death from renal causes) and key secondary outcome (time to first onset of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure) were analyzed by history of AFF. RESULTS Of 5,674 patients, 461 (8.1%) had a history of AFF. New-onset AFF occurred in 82 (3.2%) patients on finerenone and 117 (4.5%) patients on placebo (hazard ratio: 0.71; 95% confidence interval: 0.53-0.94; p = 0.016). The effect of finerenone on primary and key secondary kidney and cardiovascular outcomes was not significantly impacted by baseline AFF (interaction p value: 0.16 and 0.85, respectively). CONCLUSIONS In patients with CKD and T2D, finerenone reduced the risk of new-onset AFF. The risk of kidney or cardiovascular events was reduced irrespective of history of AFF at baseline. (EudraCT 2015-000990-11 [A randomized, double-blind, placebo-controlled, parallel-group, multicenter, event-driven Phase III study to investigate the efficacy and safety of finerenone, in addition to standard of care, on the progression of kidney disease in subjects with type 2 diabetes mellitus and the clinical diagnosis of diabetic kidney disease]; Efficacy and Safety of Finerenone in Subjects With Type 2 Diabetes Mellitus and Diabetic Kidney Disease [FIDELIO-DKD]; NCT02540993)((C) 2021 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation.)

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