钠-葡萄糖协同转运蛋白 2 抑制剂恩格列净对急性心肌梗死后炎症生物标志物的影响——EMMY 试验的事后分析。
Impact of the SGLT2-inhibitor empagliflozin on inflammatory biomarkers after acute myocardial infarction - a post-hoc analysis of the EMMY trial.
机构信息
Department of Internal Medicine, Division of Cardiology, Medical University of Graz, Auenbruggerplatz 15, Graz, 8036, Austria.
Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria.
出版信息
Cardiovasc Diabetol. 2023 Jul 5;22(1):166. doi: 10.1186/s12933-023-01904-6.
BACKGROUND
SGTL2-inhibitors are a cornerstone in the treatment of heart failure, but data on patients with acute myocardial infarction (AMI) is limited. The EMMY trial was the first to show a significant reduction in NTproBNP levels as well as improved cardiac structure and function in post-AMI patients treated with Empagliflozin compared to placebo. However, data on the potential impact of SGLT2-inhibitors on inflammatory biomarkers after AMI are scarce.
MATERIALS AND METHODS
The EMMY trial is an investigator-initiated, multicentre, double-blind, placebo-controlled trial, which enrolled patients after AMI, receiving either 10 mg Empagliflozin once daily or placebo over a period of 26 weeks on top of standard guideline-recommended therapy starting within 72 h after percutaneous coronary intervention. In this post-hoc subgroup analysis of the EMMY trial, we investigated inflammatory biomarkers of 374 patients. The endpoints investigated were the mean change in inflammatory biomarkers such as high-sensitive c-reactive protein (hsCRP), interleukin-6 (IL-6), neutrophils, leukocytes, neutrophile/lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) from baseline to 26 weeks.
RESULTS
Baseline median (interquartile ranges) IL-6 was 17.9 pg/mL (9.0-38.7), hsCRP 18.9 mg/L (11.2-37.1), neutrophil count 7.9 x G/L (6.2-10.1), leukocyte count 10.8 x G/L (9.1-12.8) and neutrophile/lymphocyte ratio (NLR) of 0.74 (0.67-0.80). At week 26, a significant mean reduction in inflammatory biomarkers was observed, being 35.1 ± 3.2% (p < 0.001) for IL-6, 57.4 ± 0.7% (p < 0.001) for hsCRP, 26.1 ± 0.7% (p < 0.001) for neutrophils, 20.5 ± 0.6% (p < 0.001) for leukocytes, 10.22 ± 0.50% (p < 0.001) for NLR, and - 2.53 ± 0.92% for PLR (p = 0.006) with no significant difference between Empagliflozin and placebo treatment.
CONCLUSION
Trajectories of inflammatory biomarkers showed a pronounced decline after AMI, but Empagliflozin treatment did not impact this decline indicating no central role in blunted systemic inflammation mediating beneficial effects.
背景
SGLT2 抑制剂是心力衰竭治疗的基石，但急性心肌梗死（AMI）患者的数据有限。EMMY 试验是第一个表明在接受恩格列净治疗的 AMI 后患者中，与安慰剂相比，NTproBNP 水平显著降低，心脏结构和功能得到改善。然而，关于 SGLT2 抑制剂对 AMI 后炎症生物标志物潜在影响的数据很少。
材料和方法
EMMY 试验是一项由研究者发起的、多中心、双盲、安慰剂对照试验，纳入了 AMI 后接受 10mg 恩格列净每日一次或安慰剂治疗的患者，在经皮冠状动脉介入治疗后 72 小时内开始接受标准指南推荐的治疗基础上，加用恩格列净或安慰剂治疗 26 周。在 EMMY 试验的这项事后亚组分析中，我们研究了 374 例患者的炎症生物标志物。研究的终点是从基线到 26 周时炎症生物标志物（如高敏 C 反应蛋白（hsCRP）、白细胞介素 6（IL-6）、中性粒细胞、白细胞、中性粒细胞/淋巴细胞比值（NLR）和血小板/淋巴细胞比值（PLR）的平均变化。
结果
基线中位数（四分位距）IL-6 为 17.9pg/ml（9.0-38.7），hsCRP 为 18.9mg/L（11.2-37.1），中性粒细胞计数为 7.9xG/L（6.2-10.1），白细胞计数为 10.8xG/L（9.1-12.8），中性粒细胞/淋巴细胞比值（NLR）为 0.74（0.67-0.80）。在 26 周时，观察到炎症生物标志物的显著平均降低，IL-6 降低 35.1±3.2%（p<0.001），hsCRP 降低 57.4±0.7%（p<0.001），中性粒细胞降低 26.1±0.7%（p<0.001），白细胞降低 20.5±0.6%（p<0.001），NLR 降低 10.22±0.50%（p<0.001），PLR 降低-2.53±0.92%（p=0.006），恩格列净与安慰剂治疗之间无显著差异。
结论
AMI 后炎症生物标志物的变化轨迹明显下降，但恩格列净治疗并未影响这种下降，表明其在介导有益作用的全身炎症迟钝中没有核心作用。
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