Effect Of Saxagliptin On LV Structure And Function In Patients With Type 2 Diabetes And Heart Failure: Results Of Measure-HF

Abstract

Introduction Further investigation was suggested by the SAVOR-TIMI 53 results regarding the risk of hospitalisation for heart failure (HF) and the dipeptidyl-peptidase 4 inhibitor saxagliptin (SAXA), especially for high-risk patients with type 2 diabetes (T2D) and established HF with reduced ejection fraction (HFrEF). The Measure-HF Trial investigated the effect of SAXA on left ventricular (LV) structure, function and N-terminal pro-brain natriuretic peptide (NT-proBNP) in patients with T2D and established symptomatic heart failure with LV ejection fraction (LVEF) &lt 45% (HFrEF) and NT-proBNP &gt 300 pg/mL. Methods Patients were randomised to SAXA (n=112), sitagliptin (SITA, n=115) or placebo (PBO, n=121) plus usual care for 24 weeks. Primary endpoint was change from baseline in LV end diastolic volume index (LVEDVi) measured by MRI (core laboratory). Secondary endpoints included changes in LV end systolic volume index (LVESVi), LVEF, LV mass, and NT-proBNP levels. Worsening HF events were adjudicated. Exploratory analyses also evaluated the same endpoints for SITA vs PBO. Results Mean age was 65.4 years, 68.9% male, mean LVEF 37.3%, and median NT-proBNP 941 pg/mL. Primary and secondary endpoints demonstrated no difference between SAXA vs PBO (Table). There was no significant difference in the change in NT-proBNP levels between SAXA and PBO groups. The changes in endpoints for SITA were consistent with those of SAXA. Adjudicated HF events were balanced: SAXA (5), SITA (3) and PBO (6). Conclusions In patients with T2D and HFrEF, SAXA compared with PBO produced no unfavorable effects on LV structure, function or natriuretic peptide levels. Further investigation was suggested by the SAVOR-TIMI 53 results regarding the risk of hospitalisation for heart failure (HF) and the dipeptidyl-peptidase 4 inhibitor saxagliptin (SAXA), especially for high-risk patients with type 2 diabetes (T2D) and established HF with reduced ejection fraction (HFrEF). The Measure-HF Trial investigated the effect of SAXA on left ventricular (LV) structure, function and N-terminal pro-brain natriuretic peptide (NT-proBNP) in patients with T2D and established symptomatic heart failure with LV ejection fraction (LVEF) &lt 45% (HFrEF) and NT-proBNP &gt 300 pg/mL. Patients were randomised to SAXA (n=112), sitagliptin (SITA, n=115) or placebo (PBO, n=121) plus usual care for 24 weeks. Primary endpoint was change from baseline in LV end diastolic volume index (LVEDVi) measured by MRI (core laboratory). Secondary endpoints included changes in LV end systolic volume index (LVESVi), LVEF, LV mass, and NT-proBNP levels. Worsening HF events were adjudicated. Exploratory analyses also evaluated the same endpoints for SITA vs PBO. Mean age was 65.4 years, 68.9% male, mean LVEF 37.3%, and median NT-proBNP 941 pg/mL. Primary and secondary endpoints demonstrated no difference between SAXA vs PBO (Table). There was no significant difference in the change in NT-proBNP levels between SAXA and PBO groups. The changes in endpoints for SITA were consistent with those of SAXA. Adjudicated HF events were balanced: SAXA (5), SITA (3) and PBO (6). In patients with T2D and HFrEF, SAXA compared with PBO produced no unfavorable effects on LV structure, function or natriuretic peptide levels.