日本語フィールド
著者：*Shinya Fujiki, Atsushi Tanaka, Takumi Imai, Michio Shimabukuro, Hiroki Uehara, Ikuko Nakamura, Kazuo Matsunaga, Makoto Suzuki, Takeshi Kashimura, Tohru Minamino, Takayuki Inomata, Koichi Node, CANDLE Trial Investigators題名：Body fluid regulation via chronic inhibition of sodium-glucose cotransporter-2 in patients with heart failure: a post hoc analysis of the CANDLE trial 発表情報：Clin Res Cardiol 巻: 112 号: 1 ページ: 87-97キーワード： Canagliflozin; Estimated extracellular volume (eEV); Estimated glomerular filtration rate (eGFR); Estimated plasma volume (ePV); HFpEF; HFrEF; Sodium?glucose cotransporter-2 (SGLT2) inhibitor概要：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: 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: 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: 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: UMIN000017669.抄録：英語フィールド
Author：*Shinya Fujiki, Atsushi Tanaka, Takumi Imai, Michio Shimabukuro, Hiroki Uehara, Ikuko Nakamura, Kazuo Matsunaga, Makoto Suzuki, Takeshi Kashimura, Tohru Minamino, Takayuki Inomata, Koichi Node, CANDLE Trial InvestigatorsTitle：Body fluid regulation via chronic inhibition of sodium-glucose cotransporter-2 in patients with heart failure: a post hoc analysis of the CANDLE trial Announcement information:Clin Res Cardiol Vol: 112 Issue: 1 Page: 87-97Keyword： Canagliflozin; Estimated extracellular volume (eEV); Estimated glomerular filtration rate (eGFR); Estimated plasma volume (ePV); HFpEF; HFrEF; Sodium?glucose cotransporter-2 (SGLT2) inhibitorAn abstract：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: 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: 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: 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: UMIN000017669.