Efficacy of Colchicine in Reducing NT-proBNP, Caspase-1, TGF-β, and Galectin-3 Expression and Improving Echocardiography Parameters in Acute Myocardial Infarction: A Multi-Center, Randomized, Placebo-Controlled, Double-Blinded Clinical Trial

秋水仙碱降低急性心肌梗死患者NT-proBNP、Caspase-1、TGF-β、Galectin-3表达及改善超声心动图参数的疗效:一项多中心、随机、安慰剂对照、双盲临床试验

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作者:Tri Astiawati, Mohammad Saifur Rohman, Titin Wihastuti, Hidayat Sujuti, Agustina Tri Endharti, Djanggan Sargowo, Delvac Oceandy, Bayu Lestari, Efta Triastuti, Ricardo Adrian Nugraha2

Background

Caspase-1 (reflects NOD-like receptor protein 3 inflammasome activity), transforming growth factor-β (TGF-β), and Galectin-3 play significant roles in post-AMI fibrosis and inflammation. Recently, colchicine was shown to dampen inflammation after AMI; however, its direct benefit remains controversial. Objectives: This study aimed to analyze the benefit of colchicine in reducing NT-proBNP, Caspase-1, TGF-β,and Galectin-3 expression and improving systolic-diastolic echocardiography parameters among AMI patients.

Conclusions

Colchicine can reduce NT-proBNP, Caspase-1, TGF-β, and Galectin-3 expression significantly among AMI patients. Colchicine administration was capable of reducing post-AMI inflammation, ventricular dysfunction, and heart failure but did not improve systolic-diastolic echocardiography parameters (ClinicalTrials.gov identifier: NCT06426537).

Methods

A double-blinded, placebo-controlled, randomized, multicenter clinical trial was conducted at three hospitals in East Java, Indonesia: Dr. Saiful Anwar Hospital Malang, Dr. Soebandi Hospital Jember, and Dr. Iskak Hospital Tulungagung, between 1 June and 31 December 2023. A total of 161 eligible AMI subjects were randomly allocated 1:1 to colchicine (0.5 mg daily) or standard treatment for 30 days. Caspase-1, TGF-β, and Galectin-3 were tested on day 1 and day 5 by ELISA, while NT-proBNP was tested on days 5 and 30. Transthoracic echocardiography was also performed on day 5 and day 30.

Results

By day 30, no significant improvements in systolic-diastolic echocardiography parameters had been shown in the colchicine group. However, colchicine reduced the level of NT-proBNP on day 30 more than placebo (ΔNT-proBNP: -73.74 ± 87.53 vs. -75.75 ± 12.44 pg/mL; p < 0.001). Moreover, colchicine lowered the level of Caspase-1 expression on day 5 and the levels of TGF-β and Galectin-3 expression on day 1. Conclusions: Colchicine can reduce NT-proBNP, Caspase-1, TGF-β, and Galectin-3 expression significantly among AMI patients. Colchicine administration was capable of reducing post-AMI inflammation, ventricular dysfunction, and heart failure but did not improve systolic-diastolic echocardiography parameters (ClinicalTrials.gov identifier: NCT06426537).

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