Effects of Vildagliptin on Ventricular Function in Patients With Type 2 Diabetes Mellitus and Heart Failure
Effects of Vildagliptin on Ventricular Function in Patients With Type 2 Diabetes Mellitus and Heart Failure
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DOI：
10.1016/j.jchf.2017.08.004
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发表时间：
2018-01-01
影响因子：
13
通讯作者：
Krum, Henry
中科院分区：
文献类型：
--
作者：
McMurray, John J. V.;Ponikowski, Piotr;Krum, Henry
目的本研究旨在探讨二肽基肽酶-4抑制剂维达格列汀在心力衰竭和射血分数降低患者中的安全性。背景：许多2型糖尿病患者都有心力衰竭，了解新的糖尿病治疗方法对这些患者的安全性是很重要的。方法18-85岁的2型糖尿病合并心力衰竭患者(纽约心脏协会功能I级到III级，左心室射血分数[LVEF]和0.40)随机分为52周，每天服用维达格列汀50 mg(如果使用磺脲类药物，每天一次，50 mg)或匹配的安慰剂。主要终点是超声心动图左心室射血分数与治疗前相比的变化，非劣值范围为-3.5%。结果共有254名患者被随机分配到维达格列汀(n=128)或安慰剂(n=126)。维拉格列汀组的基线LVEF为30.6+/-6.8%，安慰剂组为29.6+/-7.7%。维达格列汀治疗组和安慰剂组的调整后平均左心室射血分数变化分别为4.95+/-1.25%和4.33+/-1.23%，相差0.62(95%可信区间[CI]：-2.21至3.44；p=0.667)。这一差异达到了预先定义的-3.5%的非自卑边际。维格列汀组左心室舒张末和收缩末期容量分别增加17.1ml(95%可信区间：4.6ml~29.5ml；p=0.007)和9.4ml(95%可信区间：-0.49ml~19.4ml；p=0.062)。从基线到16周，维达格列汀组的主要次要终点--血红蛋白A(1c)的下降幅度更大：-0.62%(95%CI：-0.93~-0.30%；P<；0.001；-6.8mmoL/m ol；95%CI：-10.2~-3.3mmoL/m ol)。结论与安慰剂相比，维达格列汀对左心室射血分数没有重大影响，但确实导致了左室容量的增加，其原因和临床意义尚不清楚。二肽基肽酶-4抑制剂在心力衰竭和左心室收缩功能不全患者中的安全性还需要更多的证据。(Vildagliptin对2型糖尿病和充血性心力衰竭患者左心功能的影响；NCT00894868)(C)2018年，美国心脏病学会基金会。
OBJECTIVES This study sought to examine the safety of the dipeptidyl peptidase-4 inhibitor, vildagliptin, in patients with heart failure and reduced ejection fraction.BACKGROUND Many patients with type 2 diabetes mellitus have heart failure and it is important to know about the safety of new treatments for diabetes in these individuals.METHODS Patients 18 to 85 years of age with type 2 diabetes and heart failure (New York Heart Association functional class I to III and left ventricular ejection fraction [LVEF] < 0.40) were randomized to 52 weeks treatment with vildagliptin 50 mg twice daily (50 mg once daily if treated with a sulfonylurea) or matching placebo. The primary endpoint was between-treatment change from baseline in echocardiographic LVEF using a noninferiority margin of -3.5%.RESULTS A total of 254 patients were randomly assigned to vildagliptin (n = 128) or placebo (n = 126). Baseline LVEF was 30.6 +/- 6.8% in the vildagliptin group and 29.6 +/- 7.7% in the placebo group. The adjusted mean change in LVEF was 4.95 +/- 1.25% in vildagliptin treated patients and 4.33 +/- 1.23% in placebo treated patients, a difference of 0.62 (95% confidence interval [CI]: -2.21 to 3.44; p = 0.667). This difference met the predefined noninferiority margin of -3.5%. Left ventricular end-diastolic and end-systolic volumes increased more in the vildagliptin group by 17.1 ml (95% CI: 4.6 to 29.5 ml; p = 0.007) and 9.4 ml (95% CI: -0.49 to 19.4 ml; p = 0.062), respectively. Decrease in hemoglobin A(1c) from baseline to 16 weeks, the main secondary endpoint, was greater in the vildagliptin group: -0.62% (95% CI: -0.93 to -0.30%; p < 0.001; -6.8 mmol/mol; 95% CI: -10.2 to -3.3 mmol/mol).CONCLUSIONS Compared with placebo, vildagliptin had no major effect on LVEF but did lead to an increase in left ventricular volumes, the cause and clinical significance of which is unknown. More evidence is needed regarding the safety of dipeptidyl peptidase-4 inhibitors in patients with heart failure and left ventricular systolic dysfunction. (Effect of Vildagliptin on Left Ventricular Function in Patients With Type 2 Diabetes and Congestive Heart Failure; NCT00894868) (C) 2018 by the American College of Cardiology Foundation.