恩格列净对心力衰竭患者生长分化因子 15 的影响：一项随机对照试验（Empire HF Biomarker）。
The effect of empagliflozin on growth differentiation factor 15 in patients with heart failure: a randomized controlled trial (Empire HF Biomarker).
机构信息
Department of Cardiology, Research Unit of Cardiology, Odense University Hospital, Odense, Denmark.
Steno Diabetes Center Odense, Odense University Hospital, Odense, Denmark.
出版信息
Cardiovasc Diabetol. 2022 Feb 27;21(1):34. doi: 10.1186/s12933-022-01463-2.
BACKGROUND
Plasma growth differentiation factor-15 (GDF-15) biomarker levels increase in response to inflammation and tissue injury, and increased levels of GDF-15 are associated with increased risk of mortality in patients with heart failure with reduced ejection fraction (HFrEF). Sodium-glucose cotransporter-2 (SGLT2) inhibitors, which improve outcome in HFrEF, have been shown to increase plasma GDF-15 in diabetic patients. We aimed to investigate the effect of empagliflozin on GDF-15 in HFrEF patients.
METHODS
This Empire HF Biomarker substudy was from the multicentre, randomized, double-blind, placebo-controlled Empire HF trial that included 190 patients from June 29, 2017, to September 10, 2019. Stable ambulatory HFrEF patients with ejection fraction of ≤ 40% were randomly assigned (1:1) to empagliflozin 10 mg once daily, or matching placebo for 12 weeks. Changes from baseline to 12 weeks in plasma levels of GDF-15, high-sensitive C-reactive protein (hsCRP), and high-sensitive troponin T (hsTNT) were assessed.
RESULTS
A total of 187 patients who were included in this study, mean age was 64 ± 11 years; 85% male, 12% with type 2 diabetes, mean ejection fraction 29 ± 8, with no differences between the groups. Baseline median plasma GDF-15 was 1189 (918-1720) pg/mL with empagliflozin, and 1299 (952-1823) pg/mL for placebo. Empagliflozin increased plasma GDF-15 compared to placebo (adjusted between-groups treatment effect; ratio of change (1·09 [95% confidence interval (CI), 1.03-1.15]: p = 0.0040). The increase in plasma GDF15 was inversely associated with a decrease in left ventricular end-systolic (R = - 0.23, p = 0.031), and end-diastolic volume (R = - 0.29, p = 0.0066). There was no change in plasma hsCRP (1.09 [95%CI, 0.86-1.38]: p = 0.48) or plasma hsTNT (1.07 [95%CI, 0.97-1.19]: p = 0.18) compared to placebo. Patients with diabetes and treated with metformin demonstrated no increase in plasma GDF-15 with empagliflozin, p for interaction = 0·01.
CONCLUSION
Empagliflozin increased plasma levels of GDF-15 in patients with HFrEF, with no concomitant increase in hsTNT nor hsCRP.
TRIAL REGISTRATION
The Empire HF trial is registered with ClinicalTrials.gov, NCT03198585.
背景
血浆生长分化因子-15（GDF-15）生物标志物水平会因炎症和组织损伤而升高，而 GDF-15 水平升高与射血分数降低的心力衰竭（HFrEF）患者的死亡率增加相关。钠-葡萄糖共转运蛋白-2（SGLT2）抑制剂可改善 HFrEF 的预后，已被证明可增加糖尿病患者的血浆 GDF-15。我们旨在研究恩格列净对 HFrEF 患者 GDF-15 的影响。
方法
这项 Empire HF 生物标志物子研究来自多中心、随机、双盲、安慰剂对照的 Empire HF 试验，该试验纳入了 2017 年 6 月 29 日至 2019 年 9 月 10 日的 190 例患者。稳定的门诊 HFrEF 患者，射血分数≤40%，随机（1:1）分为恩格列净 10mg 每日一次，或匹配安慰剂治疗 12 周。评估基线至 12 周时血浆 GDF-15、高敏 C 反应蛋白（hsCRP）和高敏肌钙蛋白 T（hsTNT）水平的变化。
结果
共有 187 例患者纳入本研究，平均年龄为 64±11 岁；85%为男性，12%为 2 型糖尿病患者，平均射血分数为 29±8，两组间无差异。基线时恩格列净组和安慰剂组的中位血浆 GDF-15 分别为 1189（918-1720）pg/ml 和 1299（952-1823）pg/ml。与安慰剂相比，恩格列净增加了血浆 GDF-15（调整组间治疗效果；变化比（1.09 [95%置信区间（CI），1.03-1.15]：p=0.0040）。GDF15 血浆浓度的增加与左心室收缩末期（R=-0.23，p=0.031）和舒张末期容积（R=-0.29，p=0.0066）的降低呈负相关。与安慰剂相比，血浆 hsCRP（1.09 [95%CI，0.86-1.38]：p=0.48）或血浆 hsTNT（1.07 [95%CI，0.97-1.19]：p=0.18）无变化。与安慰剂相比，接受二甲双胍治疗的糖尿病患者使用恩格列净后血浆 GDF-15 无增加，p 值为 0.01。
结论
恩格列净增加了 HFrEF 患者的血浆 GDF-15 水平，同时没有增加 hsTNT 或 hsCRP。
试验注册
Empire HF 试验在 ClinicalTrials.gov 上注册，编号为 NCT03198585。
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