Myocardial Fibrosis
Conditions
Brief 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.
Detailed description
It plays an important role in preventing or delaying the occurrence of heart failure after myocardial infarction.However,even if the blood supply of infarct related vessels is restored, the immune injury, inflammatory response and RAAS activation caused by apoptotic and necrotic cardiomyocytes after myocardial infarction will still directly lead to a series of pathophysiological changes and aggravate cardiac remodeling. Based on the above targets β Receptor blockers, ACEI / ARB / Arni and aldosterone receptor antagonists have become the cornerstone of drug therapy for cardiac remodeling after myocardial infarction. However, myocardial fibrosis also plays an important role in the process of cardiac remodeling after myocardial infarction. Ischemic death of cardiomyocytes after myocardial infarction can induce repair response, and the damaged tissue is replaced by fibrotic scar produced by fibroblasts and myofibroblasts. Although the initial reparative fibrosis is very important to prevent ventricular wall rupture, excessive fibrosis and reactive fibrosis in non infarcted areas, including myocardial interstitial and perivascular fibrosis, will cause changes in cardiac morphology and biomechanics, further aggravate cardiac remodeling, damage cardiac function, and eventually lead to heart failure. Therefore, inhibition of reactive fibrosis in non infarcted areas is an important supplement to the current treatment of traditional anti cardiac remodeling drugs. In order to reduce the degree of reactive fibrosis in non infarct areas, a potentially feasible method is to inhibit the signal pathway promoting fibrosis. TGF- β Signal pathway plays an important role in promoting fibrosis signal pathway. It can promote the proliferation of fibroblasts, the differentiation and transfer of myofibroblasts, the deposition of collagen and the survival of myofibroblasts, so it can inhibit TGF- β Signal pathway is an effective method to inhibit myocardial fibrosis. Pirfenidone (PFD) is TGF- β The inhibitor can be used to delay the progression of idiopathic pulmonary fibrosis (IPF). Animal experiments also show that PFD can inhibit TGF- β Reduce myocardial fibrosis and improve the ability of myocardial contraction and relaxation. In the mouse model of dilated cardiomyopathy, it can effectively inhibit the pathological process of dilated cardiomyopathy, improve the degree of cardiac dilation and ventricular wall thickness. Preclinical studies have shown that PFD can inhibit myocardial fibrosis and protect the heart. A recently published phase II clinical study showed that compared with placebo, PFD significantly reduced EF value, preserved myocardial extracellular volume (ECV) and improved myocardial fibrosis in patients with heart failure (HFPEF). In view of the above background, we propose a research assumption: for patients after AMI, PFD drug intervention on the basis of standard treatment may achieve the effect of inhibiting myocardial fibrosis in non infarcted areas, so as to prevent or delay the occurrence of ventricular remodeling and heart failure after myocardial infarction, improve the quality of life and improve the prognosis of patients
Interventions
DRUGPirfenidone Oral Capsule
pirfenidone capsules were added to patients receiving basic treatment
OTHERPlacebo Oral Capsule
placebo oral capsules were added to patients receiving basic treatment
Sponsors
Beijing Continent Pharmaceutical Co, Ltd.
Shanghai Zhongshan Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1. Age 18 \ 80 years old (including 18 and 80 years old), regardless of gender. 2. Patients with acute anterior myocardial infarction 2-4 weeks after PCI. 3. NT proBNP ≥ 800 pg / ml in patients with sinus rhythm and 2400 pg / ml in patients with atrial fibrillation. 4. LVEF \<50%. 5. The patients volunteered to participate in the trial, with good compliance and the ability to understand and sign the informed consent before the study
Exclusion criteria
1. Those who do not meet any of the inclusion criteria. 2. Patients with non acute anterior myocardial infarction. 3. Patients without PCI after myocardial infarction. 4. Glomerular filtration rate (CKD-EPI equation) \< 30 ml / min / 1.73 m2. 5. Moderate or severe liver cirrhosis, or TBIL \> 2 times ULN, ALT or AST \> 3 times ULN caused by non cardiac reasons. 6. Patients with malignant tumors. 7. Patients with dysphagia or clinical signs of absorption disorder or requiring parenteral nutrition. 8. Patients with active peptic ulcer. 9. Severe pulmonary hypertension (pulmonary systolic pressure \> 70mmhg). 10. Other diseases or complications that may affect the participation in the trial or put the patient at risk based on the judgment of the investigator. 11. Allergic to the test drug or its components (e.g., lactose). 12. Major surgery is planned during treatment. 13. Women who are pregnant, breastfeeding or planning to become pregnant during the trial. 14. Women of childbearing age are unwilling or unable to use highly effective contraceptive methods 28 days before administration or 3 months after administration. 15. According to the researchers, the patients had alcohol or drug abuse. 16. Patients with mental illness. 17. Participate in clinical trials of other drugs. 18. The researchers judged the participants who were unwell. 19. Patients who need to use Nintedanib, pirfenidone and Amifostine at the same time.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Changes of the subjects'ECV | 52week | Compare the ECV of subjects |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Admission for heart failure | 52week | Number of participants for heart failure |
| Death | 52week | collect the case of death |
| Cardiovascular death | 52week | Number of participants with cardiovascular death |
| Changes of NT-proBNP | 52week | compare the NT-proBNP of the subjects |
| Changes of ST2 | 52week | compare the ST2 of the subjects |
| Changes of LVE | 52week | compare the LVEF of the subjects |
Countries
China
Outcome results
None listed