{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T18:32:00Z","timestamp":1774549920876,"version":"3.50.1"},"reference-count":49,"publisher":"Oxford University Press (OUP)","issue":"36","license":[{"start":{"date-parts":[[2022,7,5]],"date-time":"2022-07-05T00:00:00Z","timestamp":1656979200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,9,21]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>The sodium-glucose cotransporter-2 inhibitor empagliflozin decreases the risk of cardiovascular death or hospitalization for heart failure (HF) in patients with HF with reduced ejection fraction. Empagliflozin reduces serum uric acid (SUA), but the relevance of this effect in patients with HF is unclear. This study aimed to investigate the effect of empagliflozin on SUA levels and the therapeutic efficacy of empagliflozin in relation to SUA.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>The association between SUA and the composite primary outcome of cardiovascular death or hospitalization for worsening HF, its components, and all-cause mortality was investigated in 3676 patients of the EMPEROR-Reduced trial (98.6% of the study cohort). The treatment effect of empagliflozin was studied in relation to SUA as continuous variable, to clinical hyperuricaemia (SUA &amp;gt;5.7\u2005mg\/dL for women, &amp;gt;7.0\u2005mg\/dL for men) and in subgroups of patients of tertiles of SUA.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Hyperuricaemia was prevalent in 53% of patients with no sex differences. Elevated SUA (highest tertile, mean SUA 9.38 \u00b1\u20091.49\u2005mg\/dL) was associated with advanced severity of HF and with worst outcome [composite outcome, hazard ratio (HR) 1.64 (95% confidence interval, CI 1.28\u20132.10); cardiovascular mortality, HR 1.98 (95% CI 1.35\u20132.91); all-cause mortality, HR 1.8 (95% CI 1.29\u20132.49), all P\u2009&amp;lt;\u20090.001] in multivariate adjusted analyses, as compared with the lowest tertile. SUA was reduced following treatment with empagliflozin at 4 weeks (vs. placebo: \u22121.12\u2009\u00b1\u20090.04\u2005mg\/dL, P\u2009&amp;lt;\u20090.0001) and remained lower throughout follow-up, with a similar reduction in all prespecified subgroups. Empagliflozin reduced events of clinically relevant hyperuricaemia (acute gout, gouty arthritis or initiation of anti-gout therapy) by 32% [HR 0.68 (95% CI 0.52\u20130.89), P\u2009=\u20090.004]. The beneficial effect of empagliflozin on the primary endpoint was independent of baseline SUA [HR 0.76 (95% CI 0.65\u20130.88), P\u2009&amp;lt;\u20090.001) and of the change in SUA at 4 weeks [HR 0.81 (95% CI 0.69\u20130.95), P\u2009=\u20090.012]. As a hypothesis-generating finding, an interaction between SUA and treatment effect suggested a benefit of empagliflozin on mortality (cardiovascular and all-cause mortality) in patients in elevated SUA (P for interaction\u2009=\u20090.005 and\u2009=\u20090.011, respectively).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>Hyperuricaemia is common in HF and is an independent predictor of advanced disease severity and increased mortality. Empagliflozin induced a rapid and sustained reduction of SUA levels and of clinical events related to hyperuricaemia. The benefit of empagliflozin on the primary outcome was observed independently of SUA.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/eurheartj\/ehac320","type":"journal-article","created":{"date-parts":[[2022,7,5]],"date-time":"2022-07-05T15:26:50Z","timestamp":1657034810000},"page":"3435-3446","source":"Crossref","is-referenced-by-count":111,"title":["Uric acid and sodium-glucose cotransporter-2 inhibition with empagliflozin in heart failure with reduced ejection fraction: the EMPEROR-reduced trial"],"prefix":"10.1093","volume":"43","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7598-708X","authenticated-orcid":false,"given":"Wolfram","family":"Doehner","sequence":"first","affiliation":[{"name":"Berlin Institute of Health Center for Regenerative Therapies, and Department of Cardiology (CVK), and German Centre for Cardiovascular Research Partner Site Berlin, and Center for Stroke Research Berlin, Charit\u00e9 Universit\u00e4tsmedizin , Berlin , Germany"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3331-7314","authenticated-orcid":false,"given":"Stefan D","family":"Anker","sequence":"additional","affiliation":[{"name":"Berlin Institute of Health Center for Regenerative Therapies, and Department of Cardiology (CVK), and German Centre for Cardiovascular Research Partner Site Berlin, and Center for Stroke Research Berlin, Charit\u00e9 Universit\u00e4tsmedizin , Berlin , Germany"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4267-6933","authenticated-orcid":false,"given":"Javed","family":"Butler","sequence":"additional","affiliation":[{"name":"Baylor Heart and Vascular Institute, Baylor University Medical Center , Dallas, TX 75226 USA"},{"name":"Department of Medicine, University of Mississippi School of Medicine , Jackson, MS 39216 , USA"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7456-1570","authenticated-orcid":false,"given":"Faiez","family":"Zannad","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Lorraine, Inserm, Centre d'Investigation Clinique Plurith\u00e9matique 1433 , U1116, CHRU de Nancy, F-CRIN INI-CRCT, Nancy 54500 , France"}]},{"given":"Gerasimos","family":"Filippatos","sequence":"additional","affiliation":[{"name":"National and Kapodistrian University of Athens School of Medicine, Athens University Hospital Attikon , 12461, Haidari Athens , Greece"}]},{"given":"Jo\u00e3o Pedro","family":"Ferreira","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Lorraine, Inserm, Centre d'Investigation Clinique Plurith\u00e9matique 1433 , U1116, CHRU de Nancy, F-CRIN INI-CRCT, Nancy 54500 , France"},{"name":"UnIC@RISE, Cardiovascular Research and Development Center, Department of Surgery and Physiology, Faculty of Medicine of the University of Porto , 4200-319 Porto , Portugal"}]},{"given":"Afshin","family":"Salsali","sequence":"additional","affiliation":[{"name":"Heart Failure and Diabetes Global Development, Boehringer Ingelheim Pharmaceuticals, Inc , 900 Ridgebury Rd, Ridgefield, CT 06877 , USA"},{"name":"Faculty of Medicine, Rutgers University , New Brunswick, NJ 07103 , USA"}]},{"given":"Carolyn","family":"Kaempfer","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Rutgers University , New Brunswick, NJ 07103 , USA"},{"name":"mainanalytics GmbH, Sulzbach , Otto-Volger-Str. 3c, 65843 Sulzbach\/Taunus , Germany"}]},{"given":"Martina","family":"Brueckmann","sequence":"additional","affiliation":[{"name":"Boehringer Ingelheim International , Binger Str. 173, 55218 Ingelheim , Germany"},{"name":"First Department of Medicine, Faculty of Medicine Mannheim, University of Heidelberg , 68167 Mannheim , Germany"}]},{"given":"Stuart J","family":"Pocock","sequence":"additional","affiliation":[{"name":"Department of Medical Statistics, London School of Hygiene and Tropical Medicine , London WC1E 7HT , UK"}]},{"given":"James L","family":"Januzzi","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Massachusetts General 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