Higher baseline FIB-4 score (Q4 vs Q1) was associated with an increased risk of MACE (HR 1.48; 95% CI 1.25-1.76; P<0.0001) in patients with type 2 diabetes and atherosclerotic CV disease.
RCT
Do indices of liver steatosis and fibrosis predict cardiorenal outcomes, and does ertugliflozin affect these indices in patients with type 2 diabetes and atherosclerotic cardiovascular disease?
In patients with type 2 diabetes and ASCVD, higher baseline liver fibrosis and steatosis indices are associated with increased risk of cardiovascular events and heart failure hospitalization, while ertugliflozin treatment reduces these liver indices.
Effect estimate: HR 1.48 (95% CI 1.25-1.76)
p-value: p=<0.0001
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: , 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.
Corbin et al. (Thu,) conducted a rct in Type 2 diabetes and atherosclerotic cardiovascular disease. Ertugliflozin vs. Placebo was evaluated on Major adverse CV events (MACE) by FIB-4 score quartile (Q4 vs. Q1) (HR 1.48, 95% CI 1.25-1.76, p=<0.0001). Higher baseline FIB-4 score (Q4 vs Q1) was associated with an increased risk of MACE (HR 1.48; 95% CI 1.25-1.76; P<0.0001) in patients with type 2 diabetes and atherosclerotic CV disease.