SGLT2抑制剂联合利尿剂对CHF患者肾功能、心功能的影响及安全性研究

Effects of SGLT2 inhibitor combined with diuretics on renal and cardiac function and clinical safety in CHF patients

目的基于单中心前瞻性队列研究探索不同钠—葡萄糖共转运蛋白2(SGLT2)抑制剂联合利尿剂治疗对慢性心力衰竭(CHF)患者肾功能、心功能的影响及临床安全性。方法采用随机、开放、单中心前瞻性临床队列研究,选取2022年6月—2023年12月喀什地区第二人民医院心血管内科收治的CHF患者96例作为研究对象,通过随机数字表法分为达格列净组(n=32)、卡格列净组(n=32)和对照组(n=32),所有患者均接受常规基础心力衰竭治疗,其中达格列净组患者联合应用达格列净,卡格列净组患者联合应用卡格列净,对照组患者不额外给予药物治疗。所有患者连续治疗3个月并随访。观察患者心功能相关指标[左心室射血分数(LVEF)、左心室质量指数(LVMI)、左心室重构指数(LVRI)],心力衰竭相关血清学指标[血脑钠肽(BNP)、N端脑钠肽前体(NT-proBNP)]、心室重构相关指标[胱抑素C(CysC)、成纤维细胞生长因子23(FGF23)、基质金属蛋白酶9(MMP-9)],炎性因子[C反应蛋白(CRP)、白介素6(IL-6)、肿瘤坏死因子α(TNF-α)]、肾功能指标[血肌酐(SCr)、尿素氮(BUN)、肾小球滤过率(GFR)]及药物相关不良反应。结果治疗3个月后3组患者LVEF、LVRI、GFR均较治疗前升高,LVMI、BNP、NT-proBNP、CysC、FGF23、MMP-9、SCr和BUN水平均降低,且达格列净组、卡格列净组患者各心功能指标、心力衰竭相关血清学指标、心室重构相关指标及肾功能指标的变化幅度均大于对照组患者(F/P=13.740/<0.001、6.415/0.002、8.520/<0.001、12.184/<0.001、15.945/<0.001、14.927/<0.001、12.330/<0.001、8.755/<0.001、20.388/<0.001、12.055/<0.001、10.196/<0.001),但达格列净组、卡格列净组2组比较差异均无统计学意义(P>0.05);治疗后3组患者血清CRP、IL-6和TNF-α水平均较治疗前降低,但组间比较差异无统计学意义(F/P=0.101/0.904、1.449/0.442、0.021/0.979);3组患者不良事件发生率比较差异均无统计学意义(χ^(2)/P=0.571/0.751)。结论不论是达格列净还是卡格列净,在基础治疗方案上联合应用SGLT2抑制剂均可有效改善CHF患者的心功能及肾功能,同时显著降低患者炎性反应水平、心力衰竭相关血清学指标及心室重构程度,且具有较高的临床安全性。

Objective To explore the effects of different sodium-glucose co-transporter 2(SGLT2)inhibitors combined with diuretics on renal function,cardiac function,and clinical safety in patients with chronic heart failure(CHF).Methods A randomized,open-label,single-center prospective clinical cohort study was conducted.A total of 96 CHF patients admitted to the Second Department of Cardiology,Second People’s Hospital of Kashgar,from June 2022 to December 2023 were selected as the research subjects and divided into three groups using a random number table:the dapagliflozin group(n=32),the canagliflozin group(n=32),and the control group(n=32).All patients received conventional basic treatment for heart failure.Additionally,the dapagliflozin group was treated with dapagliflozin,the canagliflozin group with canagliflozin,and the control group without any extra medication.All patients were followed up after 3 months of continuous treatment.Observations included cardiac function-related indicators[left ventricular ejection fraction(LVEF),left ventricular mass index(LVMI),left ventricular remodeling index(LVRI)],heart failure-related serological markers[plasma brain natriuretic peptide(BNP),N-terminal pro-brain natriuretic peptide(NT-proBNP)],ventricular remodeling-related indicators[cystatin C(CysC),fibroblast growth factor 23(FGF23),matrix metalloproteinase 9(MMP-9)],inflammatory factors[C-reactive protein(CRP),interleukin-6(IL-6),tumor necrosis factor-α(TNF-α)],renal function indicators[serum creatinine(SCr),blood urea nitrogen(BUN),glomerular filtration rate(GFR)],and drug-related adverse reactions.Results After treatment,the LVEF,LVRI,and GFR of the three groups were higher than before treatment,while the levels of LVMI,BNP,NT-proBNP,CysC,FGF23,MMP-9,SCr,and BUN was lower.The changes in cardiac function indicators,heart failure-related serological markers,ventricular remodeling-related indicators,and renal function indicators in the dapagliflozin and canagliflozin groups were greater than those in the control group(F/P=13.740/<0.001,6.415/0.002,8.520/<0.001,12.184/<0.001,15.945/<0.001,14.927/<0.001,12.330/<0.001,8.755/<0.001,20.388/<0.001,12.055/<0.001,10.196/<0.001),but there was no statistically significant difference between the dapagliflozin and canagliflozin groups(P>0.05).After treatment,the serum levels of CRP,IL-6,and TNF-αin the three groups were lower than before treatment,but there was no statistically significant difference between the groups(F/P=0.101/0.904,1.449/0.442,0.021/0.979).There were no statistically significant differences in the incidence of adverse events among the three groups(χ^(2)/P=0.571/0.751).Conclusion Both dapagliflozin and canagliflozin combined with SGLT2 inhibitors on top of basic treatment can effectively improve cardiac and renal function in CHF patients,significantly reduce inflammation levels,heart failure-related serological markers,and the degree of ventricular remodeling.The combined use of different types of SGLT2 inhibitors shows high clinical safety and may have significant clinical application value for improving long-term prognosis in CHF patients.