恩格列净治疗合并不同衰弱程度的老年心力衰竭患者的预后比较

Comparison of prognosis among elderly heart failure patients with different degrees of frailty treated with Empagliflozin

目的 评估恩格列净对老年射血分数降低心力衰竭(HFrEF)患者随访1年发生主要不良心血管事件(MACE)的影响,并分析不同程度衰弱对MACE的影响.方法 回顾性队列研究,连续选取2018年1月至2020年12月在北京安贞医院住院、应用恩格列净治疗的合并HFrEF的老年2型糖尿病(T2DM)患者577例,根据衰弱指数(FI)分为3组,包括无衰弱组(FI≤0.210,301例)、中度衰弱组(FI 0.211~0.310,184例)和重度衰弱组(FI>0.311,92例).此外,纳入300例不应用钠-葡萄糖共转运蛋白2(SGLT-2)抑制剂治疗的合并T2DM老年HFrEF患者作为对照组.记录并比较各组患者出院后随访1年的MACE,包括心源性死亡、心力衰竭加重再入院、非致死性心肌梗死和非致死性卒中的复合结局,Cox回归分析影响MACE的相关因素.结果 877例患者中,随访时间7~14个月,中位随访(11.4±2.3)个月,失访47例(5.4%).随访期间恩格列净组共有108例(18.7%)发生MACE,包括43例(7.5%)心力衰竭加重再入院、29例(5.0%)非致死性心肌梗死、23例(4.0%)非致死性卒中和13例(2.3%)心血管死亡.对照组共有73例发生MACE,包括33例(11.0%)心力衰竭加重再入院、18例(6.0%)非致死性心肌梗死、14例(4.7%)非致死性卒中和8例(2.7%)心血管死亡.Kaplan-Meier生存分析结果显示,各组的心力衰竭加重再入院风险和MACE风险差异均有统计学意义.与对照组比较,恩格列净组的MACE发生风险显著降低(18.7%比24.3%,HR=0.792,95%CI:0.639~0.982,P=0.033).其中,随着衰弱程度水平的加重,恩格列净各亚组MACE的发生风险也显著增加(14.6%比19.6%比30.4%,P<0.001).与无衰弱组比较,中度和重度衰弱组患者的MACE的发生风险分别为1.342倍(HR=1.342,95%CI:1.116~1.768,P=0.022)和 1.933 倍(HR=1.933,95%CI:1.207~3.854,P=0.019).多因素 Cox 回归分析结果显示,年龄(HR=1.164)、心力衰竭病程(HR=1.225)、B型利钠肽水平(HR=1.221)、白蛋白/肌酐比(HR=1.158)、肾素-血管紧张素-醛固酮系统阻断剂(HR=0.891)、衰弱指数(HR=1.764)和使用恩格列净(HR=0.792)均与MACE的发生风险独立相关(均P<0.05).结论 恩格列净可降低HFrEF患者的MACE发生风险,但衰弱影响SGLT-2抑制剂对老年心力衰竭患者的心血管获益;随着衰弱加重,心力衰竭加重再入院和MACE发生风险明显增加.

Objective To evaluate the effect of Empagliflozin on the incidence of major adverse cardiovascular events(MACE)in elderly patients with heart failure and reduced ejection fraction(HFrEF)over a period of 1 year.Additionally,the study will analyze the influence of frailty on MACE.Methods This study is a retrospective analysis of 577 elderly patients with type 2 diabetes and heart failure with reduced ejection fraction(HFrEF)who were consecutively admitted to Beijing Anzhen Hospital from January 2018 to December 2020.The patients were divided into three groups according to frailty index(FI):non-frailty(FI≤0.210,301 cases),moderate frailty(FI 0.211-0.310,184 cases),and severe frailty(FI>0.311,92 cases).Additionally,a control group of 300 elderly HFrEF patients with T2DM who did not receive Sodium glucose co-transporter type 2(SGLT-2)inhibitors was included.The MACE outcomes of different patient groups who were followed up for a year after discharge were compared.The composite outcomes of cardiac death,worsening heart failure readmission,non-fatal myocardial infarction,and non-fatal stroke were recorded and analyzed.The study also includes Cox regression analysis of relevant factors that may affect MACE outcomes.Results A total of 877 patients were monitored for a period of 7-14 months,with a median follow-up duration of(11.4±2.3)months.Out of these patients,47(5.4%)were lost to follow-up.During the follow-up period,108 patients(18.7%)in the Empagliflozin group experienced major adverse cardiovascular events(MACE),which included 43 patients(7.5%)with heart failure readmission,29 patients(5.0%)with non-fatal myocardial infarction,23 patients(4.0%)with non-fatal stroke,and 13 patients(2.3%)with cardiovascular death.The control group had 73 cases of major adverse cardiac events(MACE),which included 33 cases(11.0%)of readmission due to heart failure,18 cases(6.0%)of non-fatal myocardial infarction,14 cases(4.7%)of non-fatal stroke,and 8 cases(2.7%)of cardiovascular death.The Kaplan-Meier survival analysis revealed significant differences in the risk of readmission for heart failure exacerbation and MACE among the groups.The study found that the Empagliflozin group had a significantly lower risk of MACE(18.7%vs.24.3%,HR=0.792,95%CI:0.639-0.982,P=0.033)compared to the control group.Additionally,as frailty level increased,the risk of MACE in each empagliflozin subgroup also increased significantly(14.6%vs.19.6%vs.30.4%,P<0.001).The moderate and severe frailty groups had a 1.342 times(HR=1.342,95%CI:1.116-1.768,P=0.022)and 1.933 times(HR=1.933,95%CI:1.207-3.854,P=0.019)higher risk of MACE compared to the non-frailty group.The study conducted a multivariate Cox regression analysis and found that several factors were independently associated with the risk of MACE,including age(HR=1.164),duration of heart failure(HR=1.225),B-type natriuretic peptide level(HR=1.221),albumin/creatinine ratio(HR=1.158),renin-angiotensin-aldosterone system blocker(HR=0.891),frailty index(HR=1.764),and empagliflozin(HR=0.792)(P<0.05 for all).Conclusions Empagliflozin has been shown to reduce the risk of major adverse cardiovascular events(MACE)in patients with heart failure with reduced ejection fraction(HFrEF).However,it is important to note that the cardiovascular benefits of SGLT-2 inhibitors may be affected by frailty in elderly patients with heart failure.As frailty worsens,the risk of readmission and MACE may increase significantly.