Journal Article

Effects of canagliflozin on NT-proBNP stratified by left ventricular diastolic function in patients with type 2 diabetes and chronic heart failure: a sub analysis of the CANDLE trial

Kida, Keisuke, Eguchi, Kazuo, Dohi, Kaoru, Node, Koichi, Kusunose, Kenya, Takeishi, Yasuchika, Ohte, Nobuyuki, Teragawa, Hiroki, Sata, Masataka, Imai, Takumi, Shiina, Kazuki, Yamada, Takahisa, Yamada, Hirotsugu, Tanaka, Atsushi

2021

Overview

Background Identification of the effective subtypes of treatment for heart failure (HF) is an essential topic for optimizing treatment of the disorder. We hypothesized that the beneficial effect of SGLT2 inhibitors (SGLT2i) on the levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) might depend on baseline diastolic function. To elucidate the effects of SGLT2i in type 2 diabetes mellitus (T2DM) and chronic HF we investigated, as a post-hoc sub-study of the CANDLE trial, the effects of canagliflozin on NT-proBNP levels from baseline to 24 weeks, with the data stratified by left ventricular (LV) diastolic function at baseline. Methods Patients (n = 233) in the CANDLE trial were assigned randomly to either an add-on canagliflozin (n = 113) or glimepiride treatment groups (n = 120). The primary endpoint was a comparison between the two groups of the changes from baseline to 24 weeks in NT-pro BNP levels, stratified according to baseline ventricular diastolic function. Results The change in the geometric mean of NT-proBNP level from baseline to 24 weeks was 0.98 (95% CI 0.89–1.08) in the canagliflozin group and 1.07 (95% CI 0.97–1.18) in the glimepiride group. The ratio of change with canagliflozin/glimepiride was 0.93 (95% CI 0.82–1.05). Responder analyses were used to investigate the response of an improvement in NT-proBNP levels. Although the subgroup analyses for septal annular velocity (SEP-e′) showed no marked heterogeneity in treatment effect, the subgroup with an SEP-e′ < 4.7 cm/s indicated there was an association with lower NT-proBNP levels in the canagliflozin group compared with that in the glimepiride group (ratio of change with canagliflozin/glimepiride (0.83, 95% CI 0.66–1.04). Conclusions In the subgroup with a lower LV diastolic function, canagliflozin showed a trend of reduced NT-pro BNP levels compared to that observed with glimepiride. This study suggests that the beneficial effects of canagliflozin treatment may be different in subgroups classified by the severity of LV diastolic dysfunction.

• Publisher: BioMed Central,Springer Nature B.V,BMC
• Subject: Aged / Angiology / Antidiabetics / Biomarkers - blood / Blood Glucose - drug effects / Blood Glucose - metabolism / Brain natriuretic peptide / Canagliflozin / Canagliflozin - adverse effects / Canagliflozin - therapeutic use / Cardiology / Congestive heart failure / Diabetes / Diabetes mellitus (non-insulin dependent) / Diabetes Mellitus, Type 2 - blood / Diabetes Mellitus, Type 2 - diagnosis / Diabetes Mellitus, Type 2 - drug therapy / Diastole / Diastolic function / Echocardiography / Ejection fraction / Female / Heart failure / Heart Failure - blood / Heart Failure - diagnosis / Heart Failure - drug therapy / Heart Failure - physiopathology / Humans / Japan / Laboratories / Male / Medicine / Medicine & Public Health / Middle Aged / Natriuretic Peptide, Brain - blood / NT-proBNP / Original Investigation / Patients / Peptide Fragments - blood / Prospective Studies / Sodium-Glucose Transporter 2 Inhibitors - adverse effects / Sodium-Glucose Transporter 2 Inhibitors - therapeutic use / Time Factors / Treatment Outcome / Type 2 diabetes mellitus / Ventricle / Ventricular Dysfunction, Left - blood / Ventricular Dysfunction, Left - diagnosis / Ventricular Dysfunction, Left - drug therapy / Ventricular Dysfunction, Left - physiopathology / Ventricular Function, Left - drug effects