• EMPA-KIDNEY Collaborative Group, William G Herrington, Natalie Staplin, Nikita Agrawal, Christoph Wanner, Jennifer B Green, Sibylle J Hauske, Jonathan R Emberson, David Preiss, Parminder Judge, Doreen Zhu, Rejive Dayanandan, Ryoki Arimoto, Kaitlin J Mayne, Sarah Y A Ng, Emily Sammons, Michael Hill, Will Stevens, Karl Wallendszus, Susanne Brenner, Alfred K Cheung, Zhi-Hong Liu, Jing Li, Lai Seong Hooi, Wen Liu, Takashi Kadowaki, Masaomi Nangaku, Adeera Levin, CherneyDavid Z IDZIFrom the Renal Studies Group, Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom (W.G.H., N.S., N.A., C.W., J.R.E., D.P., P.J., D.Z., R. D, Aldo P Maggioni, Roberto Pontremoli, Rajat Deo, Shinya Goto, Xavier Rossello, Katherine R Tuttle, Dominik Steubl, Dan Massey, Martina Brueckmann, Martin J Landray, Colin Baigent, and Richard Haynes.
• From the Renal Studies Group, Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom (W.G.H., N.S., N.A., C.W., J.R.E., D.P., P.J., D.Z., R. Dayanandan, R.A., K.J.M., S.Y.A.N., E.S., W.S., K.W., M.H., M.J.L., C.B., R.H.); the University Clinic of Würzburg, Würzburg (C.W., S.B.), Boehringer Ingelheim International (S.J.H., D.S., M.B.), Elderbrook Solutions (D.M.), and the Fifth Department of Medicine, University Medical Center Mannheim (S.J.H.) and the First Department of Medicine, Faculty of Medicine Mannheim (M.B.), University of Heidelberg, Mannheim, and the Department of Nephrology, Hospital Rechts der Isar, Technical University of Munich, Munich (D.S.) - all in Germany; Duke Clinical Research Institute, Durham, NC (J.B.G.); the University of Utah, Salt Lake City (A.K.C.); the National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, Nanjing (Z.-H.L.), and Fuwai Hospital, Chinese Academy of Medical Sciences, National Center for Cardiovascular Diseases, Beijing (J.L.) - both in China; Hospital Sultanah Aminah, Johor Bahru, Malaysia (L.S.H., W.L.); the University of Tokyo School of Medicine/Toranomon Hospital (T.K.) and the University of Tokyo School of Medicine (M.N.), Tokyo, and Tokai University School of Medicine, Isehara (S.G.) - all in Japan; the University of British Columbia, Vancouver (A.L.), and the University of Toronto, Toronto (D.Z.I.C.) - both in Canada; Università degli Studi and IRCCS Ospedale Policlinico San Martino di Genova, Genoa (R.P.), and Associazione Nazionale Medici Cardiologi Ospedalieri Research Center, Florence (A.P.M.) - both in Italy; the University of Pennsylvania Perelman School of Medicine, Philadelphia (R. Deo); Providence Health Care and University of Washington, Seattle (K.R.T.); and Hospital Universitario Son Espases, Health Research Institute of the Balearic Islands, Universitat Illes Balears, Palma de Mallorca, Spain (X.R.).
• N. Engl. J. Med. 2024 Oct 25.

BackgroundIn the EMPA-KIDNEY trial, empagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, had positive cardiorenal effects in patients with chronic kidney disease who were at risk for disease progression. Post-trial follow-up was designed to assess how the effects of empagliflozin would evolve after the discontinuation of the trial drug.MethodsIn the active trial, patients with chronic kidney disease were randomly assigned to receive either empagliflozin (10 mg once daily) or matching placebo and were followed for a median of 2 years. All the patients had an estimated glomerular filtration rate (eGFR) of at least 20 but less than 45 ml per minute per 1.73 m2 of body-surface area or an eGFR of at least 45 but less than 90 ml per minute per 1.73 m2 with a urinary albumin-to-creatinine ratio (with albumin measured in milligrams and creatinine measured in grams) of at least 200. Subsequently, surviving patients who consented were observed for 2 additional years. No trial empagliflozin or placebo was administered during the post-trial period, but local practitioners could prescribe open-label SGLT2 inhibitors, including open-label empagliflozin. The primary composite outcome was kidney disease progression or cardiovascular death as assessed from the start of the active-trial period to the end of the post-trial period.ResultsOf the 6609 patients who had undergone randomization in the active trial, 4891 (74%) were enrolled in the post-trial period. During this period, the use of open-label SGLT2 inhibitors was similar in the two groups (43% in the empagliflozin group and 40% in the placebo group). During the combined active- and post-trial periods, a primary-outcome event occurred in 865 of 3304 patients (26.2%) in the empagliflozin group and in 1001 of 3305 patients (30.3%) in the placebo group (hazard ratio, 0.79; 95% confidence interval [CI], 0.72 to 0.87). During the post-trial period only, the hazard ratio for a primary-outcome event was 0.87 (95% CI, 0.76 to 0.99). During the combined periods, the risk of kidney disease progression was 23.5% in the empagliflozin group and 27.1% in the placebo group; the risk of the composite of death or end-stage kidney disease was 16.9% and 19.6%, respectively; and the risk of cardiovascular death was 3.8% and 4.9%, respectively. There was no effect of empagliflozin on death from noncardiovascular causes (5.3% in both groups).ConclusionsIn a broad range of patients with chronic kidney disease at risk for progression, empagliflozin continued to have additional cardiorenal benefits for up to 12 months after it was discontinued. (Funded by Boehringer Ingelheim and others; EMPA-KIDNEY ClinicalTrials.gov number, NCT03594110; EuDRACT number, 2017-002971-24.).Copyright © 2024 Massachusetts Medical Society.

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