Abstract
BackgroundIdentification 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.MethodsPatients (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.ResultsThe 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).ConclusionsIn 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.
Highlights
Large clinical trials in patients with type 2 diabetes mellitus (T2DM) have reported that sodium-glucose co-transporter-2 inhibitors (SGLT2i) improve cardiovascular outcomes, especially the risk of hospitalizationKusunose et al Cardiovasc Diabetol (2021) 20:186 for heart failure (HF) [1,2,3]
HF types are generally categorized according to symptoms and systolic function stratified by ejection fraction (EF) [5]
To elucidate the effects of SGLT2 inhibitors (SGLT2i) in T2DM, we investigated the effects of canagliflozin on NT-proBNP levels stratified by baseline left ventricular diastolic function as a sub-study of the CANDLE trial
Summary
Large clinical trials in patients with type 2 diabetes mellitus (T2DM) have reported that sodium-glucose co-transporter-2 inhibitors (SGLT2i) improve cardiovascular outcomes, especially the risk of hospitalizationKusunose et al Cardiovasc Diabetol (2021) 20:186 for heart failure (HF) [1,2,3]. Large clinical trials in patients with type 2 diabetes mellitus (T2DM) have reported that sodium-glucose co-transporter-2 inhibitors (SGLT2i) improve cardiovascular outcomes, especially the risk of hospitalization. A meta-analysis of these large trials in patients with T2DM showed that SGLT2i reduced the risk of hospitalization for HF [4]. Identification of the effective subtypes of treatment for heart failure (HF) is an essential topic for optimizing treatment of the disorder. 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
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