Cardiorenal outcomes by indices of liver steatosis and fibrosis in individuals with type 2 diabetes and atherosclerotic cardiovascular disease: Analyses from VERTIS CV,a randomized trial of the sodium-glucose cotransporter-2 inhibitor ertugliflozin |
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Authors: | Karen D Corbin PhD Samuel Dagogo-Jack MD Christopher P Cannon MD David ZI Cherney MD Francesco Cosentino MD Robert Frederich MD Jie Liu MD Annpey Pong PhD Jianxin Lin MS Nilo B Cater MD Richard E Pratley MD |
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Institution: | 1. AdventHealth Translational Research Institute, Orlando, Florida, USA;2. University of Tennessee Health Science Center, Memphis, Tennessee, USA;3. Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA;4. University of Toronto, Toronto, Ontario, Canada;5. Unit of Cardiology, Karolinska Institute & Karolinska University Hospital, Stockholm, Sweden;6. Pfizer Inc., New York, New York, USA;7. Merck & Co., Inc., Rahway, New Jersey, USA
At the time of the analysis;8. Merck & Co., Inc., Rahway, New Jersey, USA |
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Abstract: | Aim To conduct a post hoc analysis to explore indices of hepatic steatosis/fibrosis and cardiorenal outcomes in the VERTIS CV study. Materials and Methods Patients with type 2 diabetes and atherosclerotic cardiovascular (CV) disease were randomized to ertugliflozin or placebo. Liver steatosis and fibrosis were assessed post hoc using the hepatic steatosis index (HSI) and fibrosis-4 (FIB-4) index to explore associations with cardiorenal outcomes (ertugliflozin and placebo data pooled, intention-to-treat analysis set). Cardiorenal outcomes (major adverse CV events MACE]; hospitalization for heart failure HHF]/CV death; CV death; HHF; and a composite kidney outcome) were stratified by baseline HSI and FIB-4 quartiles (Q1-Q4). Change in liver indices and enzymes over time were assessed (for ertugliflozin vs. placebo). Results Amongst 8246 participants, the mean age was 64.4 years, body mass index 32.0 kg/m2, HSI 44.0 and FIB-4 score 1.34. The hazard ratios (HRs) for MACE, HHF/CV death, CV death, and HHF by FIB-4 score quartile (Q4 vs. Q1) were 1.48 (95% confidence interval CI] 1.25, 1.76), 2.0 (95% CI 1.63, 2.51), 1.85 (95% CI 1.45, 2.36), and 2.94 (95% CI 1.98, 4.37), respectively (P < 0.0001 for all). With HSI, the incidence of HHF was higher in Q4 versus Q1 (HR 1.52 95% CI 1.07, 2.17]; P < 0.05). The kidney composite outcome did not differ across FIB-4 or HSI quartiles. Liver enzymes and HSI decreased over time with ertugliflozin. Conclusion In VERTIS CV, higher FIB-4 score was associated with CV events. HSI correlated with HHF. Neither measure was associated with the composite kidney outcome. Ertugliflozin was associated with a reduction in liver enzymes and HSI. |
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Keywords: | cardiovascular disease fibrosis-4 score hepatic steatosis index SGLT2 inhibitor type 2 diabetes mellitus |
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