TOPLINE

A post hoc analysis showed that, compared with placebo, dapagliflozin was associated with a lower risk for major adverse cardiovascular events (MACEs) and the composite outcome of cardiovascular (CV) death and hospitalizations for heart failure (HF) in patients with type 2 diabetes (T2D) who were at a high risk for advanced liver fibrosis.

METHODOLOGY

• The rise in obesity and T2D has increased the prevalence of advanced liver fibrosis and associated CV risk. SGLT2 inhibitors such as dapagliflozin can reduce the CV risk, but their effect across different levels of risk for fibrosis remains unclear.
• Researchers conducted a post hoc analysis of the DECLARE-TIMI 58 trial to assess the prognostic value of the fibrosis-4 (FIB-4) score for CV outcomes and to determine whether dapagliflozin reduces CV events in 16,361 patients with T2D and either established atherosclerotic CV disease or multiple CV risk factors (mean age, 63.8 years).
• Patients were randomly assigned to receive either dapagliflozin (10 mg daily) or placebo; for the analysis, study participants were stratified on the basis of their baseline FIB-4 scores into three groups: those with a low risk (< 1.30; n = 9084), intermediate risk (1.30 to < 2.67; n = 6656), and high risk (≥ 2.67; n = 621) for advanced liver fibrosis.
• The outcomes of interest were MACEs (defined as a composite of CV death, myocardial infarction, and ischemic stroke events) and a composite of CV death and hospitalization for HF.
• The median follow-up duration was 4.2 years.

TAKEAWAY

• In the placebo arm, patients with FIB-4 ≥ 2.67 had the highest event rates: 38.9 per 1000 person-years for MACEs and 28.1 for the composite of CV death and hospitalization for HF.
• In the high-risk FIB-4 group, the use of dapagliflozin was associated with a significantly reduced risk for MACEs (hazard ratio [HR], 0.61; 95% CI, 0.38-0.97) and the composite of CV death and hospitalization for HF (HR, 0.50; 95% CI, 0.28-0.90).
• In the high‑risk FIB‑4 group, greater reductions in aspartate aminotransferase and alanine aminotransferase levels were observed with the use of dapagliflozin vs placebo during the first year of treatment.
• Serious gastrointestinal and liver events were more common in the high-risk FIB-4 group, but no hepatic events were deemed to be linked to the use of dapagliflozin.

IN PRACTICE

“[The] results [of the study] highlight the value of FIB-4 as a tool for identifying individuals with T2D at high CV risk. They also demonstrate that dapagliflozin effectively reduces the risk of some of these outcomes, especially among those with high risk of advanced liver fibrosis,” the authors wrote.

SOURCE

This study was led by Jan Oscarsson, AstraZeneca, Gothenburg, Sweden. It was published online in Diabetes, Obesity and Metabolism.

LIMITATIONS

The analysis was post hoc and not prespecified in the original study protocol. The causes of elevated FIB-4 scores were not evaluated. Additionally, a relatively small number of patients in the high-risk group limited the robustness of the findings.

DISCLOSURES

The DECLARE-TIMI 58 study received funding from AstraZeneca. Six authors declared being employees and shareholders of AstraZeneca. Some other authors reported receiving honoraria, lecture fees, research funding, or payments for lectures or advisory boards, serving as consultants, speakers, or advisers and holding other ties with pharmaceutical companies and organizations, including the study’s funding agency. One author received an honorarium from WebMD for participation in educational activities.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.