Department of Clinical Pharmacy, Faculty of Pharmacy, Kafrelsheikh University, Kafrelsheikh City, Egypt.
Department of Pharmacology & Toxicology, Faculty of Pharmacy, Damanhour University, Damanhour City, Egypt.
Cardiovasc Drugs Ther. 2023 Oct;37(5):955-964. doi: 10.1007/s10557-022-07340-0. Epub 2022 May 10.
Previous studies have shown that Trimetazidine (TMZ) improves vascular endothelial function and reduces the inflammatory process progression. However, limited data have been available regarding its effects on myocardial fibrosis following ischemia and causing left ventricular dysfunction.
To investigate the impact of TMZ adjuvant therapy for ischemic cardiomyopathy (ICM) on cardiac fibrosis, vascular endothelial function, inflammation, and myocardial functions.
This randomized, double-blind controlled clinical trial included 48 patients (aged 59.4 ± 9 years) with ICM who were randomly assigned to two groups: TMZ 35 mg twice daily and placebo in addition to conventional ICM medications. All patients received the tablets for 3 months. Both groups were then compared in terms of connective tissue growth factor (CTGF), endothelin-1 (ET-1), tumor necrosis factor-alpha (TNF-α), and some echocardiographic indices, weekly angina attacks and nitrate consumption before and after treatment.
No significant differences between CTGF, ET-1, and TNF-α levels, in addition to some echocardiographic indices, were observed between both groups before treatment. After treatment, the TMZ group had significantly lower ET-1 than the placebo group, with both groups exhibiting a substantial decrease in TNF-α and CTGF. The TMZ group had lower mean ± SD levels for TNF-α and CTGF and showed significant improvement in echocardiographic indices and weekly angina attacks after treatment.
Adjunctive TMZ therapy for ICM effectively improved vascular endothelial function and reduced inflammation. Furthermore, our exploratory findings may be used to provide new information on the potential effects of TMZ on myocardial fibrosis by downregulating CTGF.
先前的研究表明曲美他嗪（TMZ）可改善血管内皮功能并减缓炎症进程。然而，关于缺血后心肌纤维化和左心室功能障碍，TMZ 的作用的数据有限。
研究 TMZ 辅助治疗缺血性心肌病（ICM）对心肌纤维化、血管内皮功能、炎症和心肌功能的影响。
这是一项随机、双盲对照临床试验，纳入了 48 名（年龄 59.4 ± 9 岁）ICM 患者，随机分为 TMZ 组（每天两次，每次 35mg）和安慰剂组，两组均在常规 ICM 药物治疗的基础上加用 TMZ 或安慰剂。所有患者均接受治疗 3 个月。比较两组患者的结缔组织生长因子（CTGF）、内皮素-1（ET-1）、肿瘤坏死因子-α（TNF-α）和一些超声心动图指标、治疗前后每周心绞痛发作和硝酸酯类药物的使用情况。
两组患者治疗前 CTGF、ET-1 和 TNF-α 水平以及一些超声心动图指标无显著差异。治疗后，TMZ 组 ET-1 水平显著低于安慰剂组，两组 TNF-α 和 CTGF 均显著降低。TMZ 组 TNF-α 和 CTGF 的平均标准差水平较低，且治疗后超声心动图指标和每周心绞痛发作均显著改善。
ICM 辅助 TMZ 治疗可有效改善血管内皮功能，减轻炎症。此外，我们的探索性发现可能为 TMZ 通过下调 CTGF 对心肌纤维化的潜在作用提供新的信息。
