Highlights
- •Baseline N-terminal pro-brain natriuretic peptide (NT-proBNP) levels affected the extent of its decrease by canagliflozin.
- •Decrease in NT-proBNP levels was prominent in patients with a higher left ventricular ejection fraction (LVEF).
- •Baseline LVEF confounded those changes after adjusting for baseline NT-proBNP levels.
Abstract
Aim
To investigate the effect of left ventricular ejection fraction (LVEF) on the behavior
of N-terminal pro-brain natriuretic peptide (NT-proBNP) levels in patients with heart
failure and type 2 diabetes mellitus with the use of canagliflozin compared to glimepiride.
Methods
Patients (n = 233) from the CANDLE trial were randomly assigned to either the add-on
canagliflozin (n = 113) or glimepiride treatment groups (n = 120). The patients were
followed-up for 24 weeks. The NT-proBNP levels were measured at baseline and after
24 weeks. The LVEF was determined at baseline.
Results
There was a significant relationship between the baseline NT-proBNP level (X1) and
the change in NT-proBNP levels from baseline to 24 weeks (Y) in the canagliflozin
group (Y = −0.533 × X1 + 178; r = −0.860, p < 0.001). However, this relationship was not observed in the glimepiride group (p = 0.428). The baseline LVEF (X2) correlated with Y with a marginal significance in
the canagliflozin group (Y = 7.72 × X2–549; r = 0.192, p = 0.054), but no relationship was observed in the glimepiride group. In the canagliflozin
group, bivariate regression analysis showed a significant correlation between Y, X1,
and X2; Y = −0.567 × X1–6.04 × X2 + 542 (R = 0.871, p < 0.001). The partial regression coefficients of X1 (p < 0.001) and X2 (p = 0.006) significantly explained the variance in Y. The correlation coefficient for
X2 was negative. There was a significant relationship between the logarithmically
transformed NT-proBNP [ln(NT-proBNP)] at baseline (X1′) and the change in ln(NT-proBNP)
values from baseline to 24 weeks (Y′), a surrogate of the rate of change in NT-proBNP
levels, in the canagliflozin group (Y′ = −0.18 × X1′ + 0.93; r = 0.450, p = 0.001).
Conclusions
The baseline NT-proBNP level significantly affected the extent and the rate of its
decrease by canagliflozin. The reduction in NT-proBNP levels by canagliflozin was
prominent in patients with a higher LVEF at baseline. However, its confounding effect
of LVEF on canagliflozin treatment was not recognized without adjusting for the NT-proBNP
level at baseline.
Graphical abstract
Graphical Abstract
Abbreviations:
DM (diabetes mellitus), HF (heart failure), HFpEF (heart failure with preserved ejection fraction), HFrEF (heart failure with reduced ejectionfraction), LV (left ventricular), LVEF (left ventricular ejection fraction), NT-proBNP (N-terminal pro-brain natriuretic peptide), SGLT2 (sodium-glucose cotransporter 2)Keywords
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Article info
Publication history
Published online: December 14, 2022
Accepted:
November 13,
2022
Received in revised form:
November 11,
2022
Received:
October 13,
2022
Publication stage
In Press Corrected ProofIdentification
Copyright
© 2022 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.
