{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T22:30:58Z","timestamp":1777501858869,"version":"3.51.4"},"reference-count":24,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T00:00:00Z","timestamp":1771372800000},"content-version":"vor","delay-in-days":109,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2025,11,9]],"date-time":"2025-11-09T00:00:00Z","timestamp":1762646400000},"content-version":"vor","delay-in-days":8,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2025,11,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>The efficacy of sodium\u2013glucose co-transporter 2 inhibitors (SGLT2i) among patients with cardiovascular-kidney-metabolic (CKM) conditions who experience severe estimated glomerular filtration rate (eGFR) deterioration during follow-up is not well established. The aim of this study was to assess the risk of cardiovascular outcomes and mortality after eGFR deterioration to &amp;lt;25\u2009ml\/min\/1.73\u2009m2 (and &amp;lt;20\u2009ml\/min\/1.73\u2009m2), and whether such eGFR deterioration modified the effect of SGLT2i across CKM populations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>Pooled analysis of placebo-controlled trials: EMPEROR-Preserved, EMPEROR-Reduced, EMPA-REG OUTCOME, CANVAS-R, and CREDENCE. Time-updated models with stratification by study were used. The median follow-up to eGFR deterioration was 17\u2009months and total follow-time was 29\u2009months. Studied outcomes included heart failure hospitalization or cardiovascular mortality, the composite of cardiovascular mortality, stroke or myocardial infarction, and all-cause mortality. Overall, 26\u2009946 patients were included, of these 1392 (5.2%) experienced eGFR deterioration to &amp;lt;25\u2009ml\/min\/1.73\u2009m2 (and 613 [2.3%] to &amp;lt;20\u2009ml\/min\/1.73\u2009m2). Factors independently associated with a higher risk of eGFR deterioration were lower baseline eGFR and higher albuminuria, whereas allocation to SGLT2i was protective. eGFR deterioration was independently associated with a nearly twofold higher risk of subsequent cardiovascular outcomes and mortality. The beneficial impact of SGLT2i treatment on cardiovascular outcomes and mortality was maintained irrespective of patients experiencing eGFR deterioration (interaction-p\u2009&amp;gt;0.1 for all outcomes). Patients who experienced eGFR deterioration were more likely to permanently discontinue treatment, without significant differences in treatment discontinuation rates between the SGLT2i and placebo groups.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Severe eGFR deterioration during follow-up was associated with an increased risk of subsequent cardiovascular events and mortality. SGLT2i reduced the probability and were beneficial irrespective of severe eGFR deterioration.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ejhf.70093","type":"journal-article","created":{"date-parts":[[2025,11,9]],"date-time":"2025-11-09T15:49:23Z","timestamp":1762703363000},"page":"2433-2441","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Sodium\u2013Glucose co-Transporter 2 Inhibitors in Severe Estimated Glomerular Filtration Rate Deterioration Across Cardiovascular-Kidney-Metabolic Conditions: A Pooled Analysis of Randomized Trials"],"prefix":"10.1093","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2304-6138","authenticated-orcid":false,"given":"Jo\u00e3o Pedro","family":"Ferreira","sequence":"first","affiliation":[{"name":"RISE-Health, Departamento de Cirurgia e Fisiologia, Faculdade de Medicina, Universidade do Porto , Porto ,","place":["Portugal"]},{"name":"Universit\u00e9 de Lorraine, INSERM, Centre d'Investigations Cliniques, CHRU de Nancy, Inserm and INI-CRCT (Cardiovascular and Renal Clinical Trialists) F-CRIN Network , Nancy ,","place":["France"]}]},{"given":"Pedro","family":"Marques","sequence":"additional","affiliation":[{"name":"RISE-Health, Departamento de Cirurgia e Fisiologia, Faculdade de Medicina, Universidade do Porto , Porto ,","place":["Portugal"]},{"name":"Servi\u00e7o de Medicina Interna, Unidade Local de Sa\u00fade S\u00e3o Jo\u00e3o , Porto ,","place":["Portugal"]}]},{"given":"Stefan D.","family":"Anker","sequence":"additional","affiliation":[{"name":"Department of Cardiology (CVK) of German Heart Center Charit\u00e9 German Centre for Cardiovascular Research (DZHK) partner site Berlin, Charit\u00e9 Universit\u00e4tsmedizin , Berlin ,","place":["Germany"]}]},{"given":"Javed","family":"Butler","sequence":"additional","affiliation":[{"name":"Baylor Scott and White Research Institute, Dallas, TX and University of Mississippi , Jackson, MS ,","place":["USA"]}]},{"given":"Gerasimos","family":"Filippatos","sequence":"additional","affiliation":[{"name":"National and Kapodistrian University of Athens School of Medicine, Athens University Hospital Attikon , Athens ,","place":["Greece"]}]},{"given":"Abhinav","family":"Sharma","sequence":"additional","affiliation":[{"name":"Research Institute of the McGill University Health Centre, McGill University , Montreal, QC ,","place":["Canada"]}]},{"given":"Francisco","family":"Vasques-N\u00f3voa","sequence":"additional","affiliation":[{"name":"RISE-Health, Departamento de Cirurgia e Fisiologia, Faculdade de Medicina, Universidade do Porto , Porto ,","place":["Portugal"]},{"name":"Servi\u00e7o de Medicina Interna, Unidade Local de Sa\u00fade S\u00e3o Jo\u00e3o , Porto ,","place":["Portugal"]}]},{"given":"Lu\u00eds","family":"Mendon\u00e7a","sequence":"additional","affiliation":[{"name":"RISE-Health, Departamento de Cirurgia e Fisiologia, Faculdade de Medicina, Universidade do Porto , Porto ,","place":["Portugal"]},{"name":"Servi\u00e7o de Nefrologia, Unidade Local de Sa\u00fade S\u00e3o Jo\u00e3o , Porto ,","place":["Portugal"]}]},{"given":"Jo\u00e3o S\u00e9rgio","family":"Neves","sequence":"additional","affiliation":[{"name":"RISE-Health, Departamento de Cirurgia e Fisiologia, Faculdade de Medicina, Universidade do Porto , Porto ,","place":["Portugal"]},{"name":"Servi\u00e7o de Endocrinologia, Unidade Local de Sa\u00fade S\u00e3o Jo\u00e3o , Porto ,","place":["Portugal"]}]},{"given":"Milton","family":"Packer","sequence":"additional","affiliation":[{"name":"Baylor University Medical Center , Dallas, TX ,","place":["USA"]},{"name":"Imperial College , London ,","place":["UK"]}]},{"given":"Faiez","family":"Zannad","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Lorraine, INSERM, Centre d'Investigations Cliniques, CHRU de Nancy, Inserm and INI-CRCT (Cardiovascular and Renal Clinical Trialists) F-CRIN Network , Nancy 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