Association between dapagliflozin, cardiac biomarkers, and cardiac remodeling in patients with diabetes mellitus and heart failure: a post-hoc analysis of a randomized study

Abstract

Abstract Introduction Sodium-glucose Cotransporter-2 (SGLT-2) inhibitors are a relatively new class of antidiabetic drugs, which showed favorable effects in heart failure (HF) patients, irrespective of their left ventricular ejection fraction (LVEF). Recent studies have demonstrated the beneficial effects of empagliflozin on cardiac function and structure, however, less is known about dapagliflozin. Purpose To investigate the association between the use of dapagliflozin and cardiac biomarkers as well as cardiac structure in a cohort of patients with HF and diabetes mellitus (DM). Methods The present was a post-hoc analysis of a recently published randomized study, which included 110 patients (Dapagliflozin group n = 56, Control group n = 54) with HF and DM. Inclusion criteria included: age>18 years, history of DM and HF, regardless of LVEF, and hospitalization for HF exacerbation within 6 months. Exclusion criteria were previous treatment with SGLT2i or Glucagon-like Peptide-1 Receptor agonists, a GFR< 30 and life expectancy< 1 year. The evaluation of patients (at baseline, 6 and 12 months) included clinical assessment, laboratory blood tests, and echocardiography. In order to investigate the changes in biomarkers and ultrasound indexes throughout the follow-up period in the two groups, linear mixed regression analyses were conducted. The regression equation included terms for time, group, time-group interaction, age and heart rate (HR) at baseline. Adjusted regression coefficients (β) with standard errors (SE) were computed from the results of the mixed models. Statistical significance was set at p< 0.05 and analyses were conducted using STATA statistical software (version 13.0). Results After adjusting for age and baseline HR, troponin decreased significantly throughout the follow-up period in a similar degree in both groups. Brain Natriuretic peptide (BNP) decreased significantly across all follow-up time points in both groups. However, the degree of decrease was significantly greater in the SGLT2-inhibitor group (Figure 1A, Table 1). LVEF did not change significantly over the follow-up period in the Control group, while it increased significantly in the SGLT2-inhibitor group. Left atrium (LA) increased significantly throughout the follow-up period only in the Control group, while in the SGLT2-inhibitor group there was no significant change. LA Volume index (Figure 1B), LV end diastolic volume (LVEDV), LVEDV index (Figure 1C), LV end systolic volume (LVESV), LVESV index and Global longitudinal strain (GLS) (Figure 1D) increased significantly throughout the follow-up period in the Control group, while in the SGLT2-inhibitor group they decreased significantly. LV mass index increased significantly throughout the follow-up period in a similar degree in both groups. Conclusion(s) Dapagliflozin, an SGLT2i, was associated with a reduction in cardiac biomarkers and with reverse cardiac remodeling in patients with HF and DM.Figure1.Longitudinal changesTable1.Results of the mixed LR analysis