부산대학교 도서관

Background: Kidney dysfunction often leads to reluctance to start or continue life-saving heart failure (HF) therapy.
Objectives: This study sought to examine the efficacy and safety of mineralocorticoid receptor antagonists (MRAs) in patients with HF with reduced ejection fraction experiencing significant kidney dysfunction.
Methods: We pooled individual patient data from the RALES (Randomized Aldactone Evaluation Study) and EMPHASIS-HF (Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure) trials. The association between MRA treatment and outcomes was assessed according to whether the estimated glomerular filtration rate (eGFR) declined to <30 mL/min/1.73 m 2 or not. The primary outcome was cardiovascular death or HF hospitalization.
Results: Among 4,355 patients included, 295 (6.8%) experienced a deterioration of eGFR after randomization to <30 mL/min/1.73 m 2 . These patients had more impaired baseline cardiac and kidney function (eGFR 47.3 ± 13.4 mL/min/1.73 m 2 vs 70.5 ± 21.8 mL/min/1.73 m 2 ) and had a higher risk of the primary outcome than patients without eGFR deterioration (HR: 2.49; 95% CI: 2.01-3.08; P < 0.001). However, the risk reduction in the primary outcome with MRA therapy was similar in those who experienced a decrease in eGFR to <30 mL/min/1.73 m 2 (HR: 0.65; 95% CI: 0.43-0.99) compared with those who did not (HR: 0.63; 95% CI: 0.56-0.71) (P interaction  = 0.87). In patients with a decrease in eGFR to <30 mL/min/1.73 m 2 , 21 fewer individuals (per 100 person-years) experienced the primary outcome with MRA treatment, vs placebo, compared with an excess of 3 more patients with severe hyperkalemia (>6.0 mmol/L).
Conclusions: Because patients experiencing a decrease in eGFR to <30 mL/min/1.73 m 2 are at very high risk, the absolute risk reduction with an MRA in these patients is large and this decline in eGFR should not automatically lead to treatment discontinuation.
Competing Interests: Funding Support and Author Disclosures Drs Jhund and McMurray were supported by a British Heart Foundation Centre of Research Excellence Grant (RE/18/6/34217) and the Vera Melrose Heart Failure Research Fund. The EMPHASIS-HF trial was sponsored by Pfizer. Dr Matsumoto has received research grants and personal fees from Abbott, Bayer Pharma, Boehringer Ingelheim, Daiichi-Sankyo, Medtronic, Novartis, Ono Pharma, Orbus Neich, Otsuka Pharma, and the Uehara Memorial Foundation. Dr Yang has received a grant from AstraZeneca to attend a medical congress. Dr Swedberg has received honoraria from AstraZeneca, Boehringer Ingelheim, and Novartis. Dr Vaduganathan has received research grant support, served on advisory boards, or had speaker engagements with American Regent, Amgen, AstraZeneca, Bayer AG, Baxter Healthcare, BMS, Boehringer Ingelheim, Chiesi, Cytokinetics, Lexicon Pharmaceuticals, Merck, Novartis, Novo Nordisk, Pharmacosmos, Relypsa, Roche Diagnostics, Sanofi, and Tricog Health; and has served on clinical trial committees for studies sponsored by AstraZeneca, Galmed, Novartis, Bayer AG, Occlutech, and Impulse Dynamics. Dr Solomon has received research grant support from Actelion, Alnylam, Amgen, AstraZeneca, Bellerophon, Bayer, Bristol Myers Squibb, Celladon, Cytokinetics, Eidos, Gilead, GlaxoSmithKline, Ionis, Lilly, Mesoblast, MyoKardia, the National Institutes of Health/National Heart, Lung, and Blood Institute, Neurotronik, Novartis, Novo Nordisk, Respicardia, Sanofi Pasteur, Theracos, and US2.AI; and has served as consulted for Abbott, Action, Akros, Alnylam, Amgen, Arena, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Cardior, Cardurion, Corvia, Cytokinetics, Daiichi-Sankyo, GlaxoSmithKline, Lilly, Merck, MyoKardia, Novartis, Roche, Theracos, Quantum Genomics, Cardurion, Janssen, Cardiac Dimensions, Tenaya, Sanofi Pasteur, Dinaqor, Tremeau, CellProthera, Moderna, American Regent, and Sarepta. Dr Pitt has served as a consultant for Bayer, AstraZeneca, Boehringer Ingelheim, Merck, Lexicon, and G3 Pharmaceuticals; owns stock options in KBP BioSciences, Vifor, Sarfez, scPharmaceuticals, SQInnovation, ProtonIntel, Cereno Scientific, and Brainstorm Medical; holds U.S. patent US9931422 (site specific delivery of eplerenone to the myocardium); and is an inventor of U.S. patent pending US63/045,783 (histone acetylation modulating agents for the protection and treatment of organ damage). Dr Zannad has received personal fees from Boehringer Ingelheim (during the conduct of the study), Janssen, Novartis, Boston Scientific, Amgen, CVRx, AstraZeneca, Vifor Fresenius, Cardior, Cereno Pharmaceutical, Applied Therapeutics, Merck, Bayer, and CellProthera; and has received other fees from CVCT and Cardiorenal, outside the submitted work. Dr Jhund has received speaker fees from AstraZeneca, Novartis, Alkem Metabolics, ProAdWise Communications, Sun Pharmaceuticals, and Intas Pharmaceuticals; has received advisory board fees from AstraZeneca, Boehringer Ingelheim, and Novartis; has received research funding from AstraZeneca, Boehringer Ingelheim, and Analog Devices Inc; his employer (University of Glasgow) has been remunerated for clinical trial work from AstraZeneca, Bayer AG, Novartis, and Novo Nordisk; and he is a director of Global Clinical Trial Partners. Dr McMurray has received payments through Glasgow University from work on clinical trials, consulting, and other activities from Amgen, AstraZeneca, Bayer, Cardurion, Cytokinetics, GSK, KBP Biosciences, and Novartis; has received personal consultancy fees from Alnylam Pharma, Bayer, BMS, George Clinical PTY Ltd, Ionis Pharmaceuticals, Novartis, Regeneron Pharmaceuticals, and River 2 Renal Corporation; has received personal lecture fees from Abbott, Alkem Metabolics, AstraZeneca, Blue Ocean Scientific Solutions Ltd, Boehringer Ingelheim, Canadian Medical and Surgical Knowledge, Emcure Pharmaceuticals Ltd, Eris Lifesciences, the European Accreditation Council of Continuing Medical Education, Hikma Pharmaceuticals, Imagica Health, Intas Pharmaceuticals, J.B. Chemicals & Pharma Pharmaceuticals Ltd, Lupin Pharmaceuticals, Medscape/Heart.org, ProAdWise Communications, Radcliffe Cardiology, Sun Pharmaceuticals, The Corpus, Translation Research Group, and the Translational Medicine Academy; and is a director of Global Clinical Trial Partners Ltd. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
(Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)