Association between uric acid levels and cardio-renal outcomes and death in patients with type 2 diabetes: A subanalysis of EMPA-REG OUTCOME |
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| Authors: | Subodh Verma MD Qiuhe Ji MD Deepak L. Bhatt MD C. David Mazer MD Mohammed Al-Omran MD Silvio E. Inzucchi MD Christoph Wanner MD Anne Pernille Ofstad MD Isabella Zwiener PhD Jyothis T. George MBBS Bernard Zinman MD David Fitchett MD |
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| Affiliation: | 1. St Michael's Hospital, Division of Cardiac Surgery, University of Toronto, Toronto, Ontario, Canada;2. Xijing Hospital, Fourth Military Medical University, Xi'an, China;3. Brigham and Women's Hospital Heart and Vascular Centre and Harvard Medical School, Boston, Massachusetts, USA;4. St Michael's Hospital, Department of Anaesthesia, University of Toronto, Toronto, Ontario, Canada;5. St Michael's Hospital, Division of Vascular Surgery, University of Toronto, Toronto, Ontario, Canada;6. Yale University School of Medicine, New Haven, Connecticut, USA;7. Würzburg University Clinic, Würzburg, Germany;8. Boehringer Ingelheim Norway KS, Asker, Norway;9. Boehringer Ingelheim Pharma GmbH & Co KG, Ingelheim, Germany;10. Boehringer Ingelheim International GmbH, Ingelheim, Germany;11. Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada;12. St Michael's Hospital, Division of Cardiology, University of Toronto, Toronto, Ontario, Canada |
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| Abstract: | In the EMPA-REG OUTCOME trial, we explored the association between pre-randomization uric acid level tertile (<309.30 μmol/L; 309.30 to <387.21 μmol/L; ≥387.21 μmol/L) and cardiovascular (CV) death, hospitalization for heart failure (HHF), HHF or CV death, all-cause mortality, three-point major adverse CV events (MACE), and incident or worsening nephropathy. Patients with type 2 diabetes and CV disease received empagliflozin or placebo. The median baseline plasma uric acid level was 344.98 μmol/L, and patients’ baseline characteristics were mainly balanced across tertiles. Baseline uric acid levels were associated with cardio-renal outcomes: in the placebo group, for the highest versus lowest tertile, the multivariable hazard ratios for three-point MACE, HHF or CV death, and incident or worsening nephropathy were 1.22 (95% confidence interval [CI] 0.89–1.67; P = 0.2088), 1.51 (95% CI 1.02–2.23; P = 0.0396) and 1.77 (95% CI 1.33–2.34; P < 0.0001), respectively. When tested as a continuous variable, baseline uric acid was associated with all outcomes in the placebo group. Empagliflozin improved all cardio-renal outcomes across tertiles, with all interaction P values >0.05. Further investigation of these relationships is required. |
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| Keywords: | cardiovascular disease clinical trial empagliflozin SGLT2 inhibitor type 2 diabetes |
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