Fujiki Shinya, Tanaka Atsushi, Imai Takumi, Shimabukuro Michio, Uehara Hiroki, Nakamura Ikuko, Matsunaga Kazuo, Suzuki Makoto, Kashimura Takeshi, Minamino Tohru, Inomata Takayuki, Node Koichi
Department of Cardiovascular Medicine, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachidori, Chuo-ku, Niigata, 951-8510, Japan.
Department of Cardiovascular Medicine, Saga University, Saga, Japan.
Clin Res Cardiol. 2023 Jan;112(1):87-97. doi: 10.1007/s00392-022-02049-4. Epub 2022 Jun 22.
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.
在慢性心力衰竭（CHF）合并2型糖尿病（T2D）患者中，钠-葡萄糖协同转运蛋白2（SGLT2）抑制剂可改善心肾结局，但对不同体液容量亚组的影响细节仍不完整。
这是对CANDLE试验（UMIN000017669）中CHF合并T2D患者的一项事后分析，该试验是一项由研究者发起的多中心随机开放标签试验，比较了卡格列净（100 mg，n = 113）与格列美脲（起始剂量：0.5 mg，n = 120）对N末端脑钠肽变化的影响。在第4、12和24周比较治疗组之间的估计血浆容量（ePV，用Straus公式计算）和估计细胞外液容量（eEV，由体表面积确定）。
在分析的233例患者中，166例（71.2%）射血分数（EF）＞50%。直到第12周，仅在卡格列净组观察到ePV和eEV降低（第12周相对于基线的变化，ePV：-7.63%；95%置信区间[CI]，-10.71至-4.55%，p＜0.001，eEV：-123.15 mL；95%CI，-190.38至-55.92 mL，p＜0.001）。虽然ePV在第12周后停止下降，但eEV持续下降直到第24周（[第24周相对于基线的变化]-[第12周相对于基线的变化]，ePV：1.01%；95%CI，-2.30至4.32%，p = 0.549，eEV：-125.15 mL；95%CI，-184.35至-65.95 mL，p＜0.001）。
通过长期SGLT2抑制维持ePV适度降低并持续清除eEV表明，有利的体液调节有助于SGLT2抑制剂对CHF患者的心肾益处，与EF无关。
UMIN000017669。
