Pirfenidone Treat Myocardial Fibrosis After Acute Myocardial Infarction

Summary

Acute myocardial infarction (AMI) is myocardial necrosis caused by acute and continuous ischemia and hypoxia of coronary artery. It can be complicated with arrhythmia, shock or heart failure, which is often life-threatening. The disease is the most common in Europe and the United States, where about 1.5 million people suffer from myocardial infarction every year. China has shown an obvious upward trend in recent years, with at least 500000 new cases every year and at least 2 million current cases . At present, China has a high incidence rate of heart failure after myocardial infarction. The incidence of heart failure within 7 days after myocardial infarction is 19.3%, and the incidence of heart failure from 30 days to 6.7 years after myocardial infarction is 13.1%\~37.5%. The incidence of heart failure after myocardial infarction significantly increases the risk of short-term and long-term death, and the prognosis is poor. At present, there is a lack of unified guidance and norms for the diagnosis, treatment and prevention and control strategies of heart failure after myocardial infarction. Cardiac remodeling is the basic pathological process of heart failure after myocardial infarction, and it is also one of the main factors affecting the prognosis of patients. Studies have shown that 30% of AMI have ventricular remodeling 6 months after percutaneous coronary intervention (PCI), and the risk of ventricular remodeling in anterior wall myocardial infarction is the highest. According to foreign literature data, the probability of ventricular remodeling after anterior wall acute myocardial infarction is about 13%, which is 1.9 times higher than that in other parts.Opening the infarct related coronary artery early can save the dying myocardium, reduce the infarct myocardial area and reduce the loss of cardiomyocytes.

Timeline

Start

2022-08-05

Primary completion

2024-05

Completion

2024-06

Publications

• Background Talman V, Ruskoaho H. Cardiac fibrosis in myocardial infarction-from repair and remodeling to regeneration. Cell Tissue Res. 2016 Sep;365(3):563-81. doi: 10.1007/s00441-016-2431-9. Epub 2016 Jun 21.
• Background Prabhu SD, Frangogiannis NG. The Biological Basis for Cardiac Repair After Myocardial Infarction: From Inflammation to Fibrosis. Circ Res. 2016 Jun 24;119(1):91-112. doi: 10.1161/CIRCRESAHA.116.303577.
• Background Lee HC, Park JS, Choe JC, Ahn JH, Lee HW, Oh JH, Choi JH, Cha KS, Hong TJ, Jeong MH; Korea Acute Myocardial Infarction Registry (KAMIR) and Korea Working Group on Myocardial Infarction (KorMI) Investigators. Prediction of 1-Year Mortality from Acute Myocardial Infarction Using Machine Learning. Am J Cardiol. 2020 Oct 15;133:23-31. doi: 10.1016/j.amjcard.2020.07.048. Epub 2020 Jul 26.
• Background Dondo TB, Hall M, Munyombwe T, Wilkinson C, Yadegarfar ME, Timmis A, Batin PD, Jernberg T, Fox KA, Gale CP. A nationwide causal mediation analysis of survival following ST-elevation myocardial infarction. Heart. 2020 May;106(10):765-771. doi: 10.1136/heartjnl-2019-315760. Epub 2019 Nov 15.
• Background Lewis GA, Dodd S, Clayton D, Bedson E, Eccleson H, Schelbert EB, Naish JH, Jimenez BD, Williams SG, Cunnington C, Ahmed FZ, Cooper A, Rajavarma Viswesvaraiah, Russell S, McDonagh T, Williamson PR, Miller CA. Pirfenidone in heart failure with preserved ejection fraction: a randomized phase 2 trial. Nat Med. 2021 Aug;27(8):1477-1482. doi: 10.1038/s41591-021-01452-0. Epub 2021 Aug 12.
• Background Graziani F, Lillo R, Crea F. Rationale for the Use of Pirfenidone in Heart Failure With Preserved Ejection Fraction. Front Cardiovasc Med. 2021 Apr 22;8:678530. doi: 10.3389/fcvm.2021.678530. eCollection 2021.
• Background Lewis GA, Schelbert EB, Naish JH, Bedson E, Dodd S, Eccleson H, Clayton D, Jimenez BD, McDonagh T, Williams SG, Cooper A, Cunnington C, Ahmed FZ, Viswesvaraiah R, Russell S, Neubauer S, Williamson PR, Miller CA. Pirfenidone in Heart Failure with Preserved Ejection Fraction-Rationale and Design of the PIROUETTE Trial. Cardiovasc Drugs Ther. 2019 Aug;33(4):461-470. doi: 10.1007/s10557-019-06876-y.
• Background Nguyen DT, Ding C, Wilson E, Marcus GM, Olgin JE. Pirfenidone mitigates left ventricular fibrosis and dysfunction after myocardial infarction and reduces arrhythmias. Heart Rhythm. 2010 Oct;7(10):1438-45. doi: 10.1016/j.hrthm.2010.04.030. Epub 2010 Apr 28.
• Background Li C, Han R, Kang L, Wang J, Gao Y, Li Y, He J, Tian J. Pirfenidone controls the feedback loop of the AT1R/p38 MAPK/renin-angiotensin system axis by regulating liver X receptor-alpha in myocardial infarction-induced cardiac fibrosis. Sci Rep. 2017 Jan 16;7:40523. doi: 10.1038/srep40523.

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