Body fluid regulation via chronic inhibition of sodium-glucose cotransporter-2 in patients with heart failure: a post hoc analysis of the CANDLE trial.
Canagliflozin
Estimated extracellular volume (eEV)
Estimated glomerular filtration rate (eGFR)
Estimated plasma volume (ePV)
HFpEF
HFrEF
Sodium–glucose cotransporter-2 (SGLT2) inhibitor
Journal
Clinical research in cardiology : official journal of the German Cardiac Society
ISSN: 1861-0692
Titre abrégé: Clin Res Cardiol
Pays: Germany
ID NLM: 101264123
Informations de publication
Date de publication:
Jan 2023
Jan 2023
Historique:
received:
19
03
2022
accepted:
31
05
2022
pubmed:
22
6
2022
medline:
21
1
2023
entrez:
21
6
2022
Statut:
ppublish
Résumé
In patients with chronic heart failure (CHF) and type 2 diabetes (T2D), sodium-glucose cotransporter-2 (SGLT2) inhibition improves cardiorenal outcomes, but details of the effects on distinct subsets of body fluid volume remain incomplete. This was a post hoc analysis of patients with CHF and T2D in the CANDLE trial (UMIN000017669), an investigator-initiated, multi-center, randomized open-label trial that compared the effect of canagliflozin (100 mg, n = 113) with glimepiride (starting dose: 0.5 mg, n = 120) on changes in N-terminal pro-brain natriuretic peptide. The estimated plasma volume (ePV, calculated with the Straus formula) and estimated extracellular volume (eEV, determined by the body surface area) were compared between treatment groups at weeks 4, 12, and 24. Among 233 patients analyzed, 166 (71.2%) had an ejection fraction (EF) > 50%. Reductions in ePV and eEV were observed only in the canagliflozin group until week 12 (change from baseline at week 12, ePV; - 7.63%; 95% confidence interval [CI], - 10.71 to - 4.55%, p < 0.001, eEV; - 123.15 mL; 95% CI, - 190.38 to - 55.92 mL, p < 0.001). While ePV stopped falling after week 12, eEV continued to fall until week 24 ([change from baseline at week 24] - [change from baseline at week 12], ePV; 1.01%; 95%CI, - 2.30-4.32%, p = 0.549, eEV; - 125.15 mL; 95% CI, - 184.35 to - 65.95 mL, p < 0.001). Maintenance of a modest reduction in ePV and continuous removal of eEV via chronic SGLT2 inhibition suggests that favorable body fluid regulation contributes to the cardiorenal benefits of SGLT2 inhibitors in patients with CHF, irrespective of EF. UMIN000017669.
Sections du résumé
BACKGROUND
BACKGROUND
In patients with chronic heart failure (CHF) and type 2 diabetes (T2D), sodium-glucose cotransporter-2 (SGLT2) inhibition improves cardiorenal outcomes, but details of the effects on distinct subsets of body fluid volume remain incomplete.
METHODS
METHODS
This was a post hoc analysis of patients with CHF and T2D in the CANDLE trial (UMIN000017669), an investigator-initiated, multi-center, randomized open-label trial that compared the effect of canagliflozin (100 mg, n = 113) with glimepiride (starting dose: 0.5 mg, n = 120) on changes in N-terminal pro-brain natriuretic peptide. The estimated plasma volume (ePV, calculated with the Straus formula) and estimated extracellular volume (eEV, determined by the body surface area) were compared between treatment groups at weeks 4, 12, and 24.
RESULTS
RESULTS
Among 233 patients analyzed, 166 (71.2%) had an ejection fraction (EF) > 50%. Reductions in ePV and eEV were observed only in the canagliflozin group until week 12 (change from baseline at week 12, ePV; - 7.63%; 95% confidence interval [CI], - 10.71 to - 4.55%, p < 0.001, eEV; - 123.15 mL; 95% CI, - 190.38 to - 55.92 mL, p < 0.001). While ePV stopped falling after week 12, eEV continued to fall until week 24 ([change from baseline at week 24] - [change from baseline at week 12], ePV; 1.01%; 95%CI, - 2.30-4.32%, p = 0.549, eEV; - 125.15 mL; 95% CI, - 184.35 to - 65.95 mL, p < 0.001).
CONCLUSIONS
CONCLUSIONS
Maintenance of a modest reduction in ePV and continuous removal of eEV via chronic SGLT2 inhibition suggests that favorable body fluid regulation contributes to the cardiorenal benefits of SGLT2 inhibitors in patients with CHF, irrespective of EF.
TRIAL REGISTRATION
BACKGROUND
UMIN000017669.
Identifiants
pubmed: 35729430
doi: 10.1007/s00392-022-02049-4
pii: 10.1007/s00392-022-02049-4
doi:
Substances chimiques
Canagliflozin
0SAC974Z85
Glucosides
0
Sodium-Glucose Transporter 2
0
Sodium-Glucose Transporter 2 Inhibitors
0
Types de publication
Randomized Controlled Trial
Multicenter Study
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
87-97Informations de copyright
© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.
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