Impact of primary kidney disease on the effects of empagliflozin in patients with chronic kidney disease: secondary analyses of the EMPA-KIDNEY trial
PK Judge, Natalie Staplin, KJ Mayne, Christoph Wanner, Julie Green, SJ Hauske, Jonathan Emberson, David Preiss, SYA Ng, AJ Roddick, Emily Sammons, Dandan Zhu, Michael Hill, W. Grant Stevens, Karl Wallendszus, Susanne Brenner, AK Cheung, Zhihong Liu, J Li, LS Hooi, Wenjun Liu, Takashi Kadowaki, Masaomi Nangaku, Adeera Levin, David Z.I. Cherney, Aldo P. Maggioni, Roberto Pontremoli, Rajat Deo, Shinichi Goto, Xavier Rosselló, Katherine R. Tuttle, Dominik Steubl, Daisy Massey, Martin Landray, Colin Baigent, Richard Haynes, WG Herrington, S Abat, Riaz Rahman, Rizna Abdul Cader, MI Abdul Hafidz, MZ Abdul Wahab, NK Abdullah, Talal Abdulsamad, Masanori Abe, Nader G. Abraham, Sarah Acheampong, P Achiri, JA Acosta, A. Q. Adeleke, Vicki Adell, R Adewuyi-Dalton, Nihad Adnan, A Africano, Mohsen Agharazii, Frank G. Aguilar, A Aguilera, Movahedian Ahmad, MK Ahmad, NA Ahmad, NH Ahmad, NI Ahmad, Norazinizah Ahmad Miswan, H Ahmad Rosdi, Iffat Ahmed, Sofia B. Ahmed, Sofia B. Ahmed, Joan Aiello, A. Aitken, R AitSadi, Sendogan Aker, S Akimoto, A Akinfolarin, S. Akram, Federico Alberici, Christian Albert, Leslie N. Aldrich, M Alegata, Lee Alexander, S Alfaress, Mohammad Alhadj Ali, Ahmed Issam Ali, Ahmed Issam Ali, Radica Z. Alicic, A Aliu, Ricardo López Almaraz, Rashid Almasarwah, Jussara Carnevale de Almeida, Alessia Aloisi, Laith Al‐Rabadi, Mark Dominik Alscher, Pedro Álvarez, Bader Al-Zeer, Mora Amat, Christopher S. Ambrose, Hany Ammar, Yu An, L Andriaccio, Kwame Ansu, A Apostolidi
Abstract
BACKGROUND: The EMPA-KIDNEY trial showed that empagliflozin reduced the risk of the primary composite outcome of kidney disease progression or cardiovascular death in patients with chronic kidney disease mainly through slowing progression. We aimed to assess how effects of empagliflozin might differ by primary kidney disease across its broad population. METHODS: , or death from kidney failure) were assessed using prespecified Cox models, and eGFR slope analyses used shared parameter models. Subgroup comparisons were performed by including relevant interaction terms in models. EMPA-KIDNEY is registered with ClinicalTrials.gov, NCT03594110. FINDINGS: per year (95% CI 1·16-1·59), representing a 50% (42-58) reduction in the rate of chronic eGFR decline. This relative effect of empagliflozin on chronic eGFR slope was similar in analyses by different primary kidney diseases, including in explorations by type of glomerular disease and diabetes (p values for heterogeneity all >0·1). INTERPRETATION: In a broad range of patients with chronic kidney disease at risk of progression, including a wide range of non-diabetic causes of chronic kidney disease, empagliflozin reduced risk of kidney disease progression. Relative effect sizes were broadly similar irrespective of the cause of primary kidney disease, suggesting that SGLT2 inhibitors should be part of a standard of care to minimise risk of kidney failure in chronic kidney disease. FUNDING: Boehringer Ingelheim, Eli Lilly, and UK Medical Research Council.