Efficacy Study of Glucagonlike Peptide-1 to Treat Reperfusion Injury

Study Overview
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Brief Summary
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The investigators planned to research the cardioprotective effects of intravenous liraglutide on reperfusion injury.

Detailed Description
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Acute myocardial infarction is a major cause of mortality and morbidity. Primary percutaneous coronary intervention (pPCI) is currently the most effective treatment strategy in acute myocardial infarction. However, a sizable number of patients fail to restore optimal myocardial reperfusion, mostly because of the 'no-reflow' phenomenon. Glucagon-like peptide-1 (GLP-1) is an incretin hormone that regulates plasma glucose, and recently GLP-1 analogues have been introduced for the treatment of type-2 diabetes. In experimental studies, GLP-1 or its analogues protect against reperfusion injury-induced cell death. Exenatide reduces reperfusion injury in patients with ST-segment elevation myocardial infarction. Liraglutide(GLP-1) is safe and effective to reduce weight,serum lipid levels and blood pressure. Liraglutide can reduce cardiac rupture (12 of 60 versus 46 of 60; P=0.0001) and infarct size (21±2% versus 29±3%, P=0.02) and improved cardiac output (12.4±0.6 versus 9.7±0.6 ml/min; P=0.002) in normal and diabetic mice. The investigators planned to research the cardioprotective effects of intravenous liraglutide administered prior to reperfusion and continued after restoration of coronary blood flow in patients with STEMI undergoing pPCI.

Official Title
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Protective Effect of Glucagonlike Peptide-1 on Reperfusion Injury in Patients With Acute Myocardial Infarction

Conditions
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Acute Myocardial Infarction

Intervention / Treatment
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* Drug: liraglutide (Novo Nordisk, Bagsværd, Denmark)
* Drug: liraglutide placebo (Novo Nordisk)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients were eligible if they were 18 years or older and presented within 12 h from the onset of symptoms and signs of ST-segment elevation myocardial infarction to the catheterization laboratory. Exclusion Criteria: The patients were not considered for enrolment if they presented with unconsciousness, cardiogenic shock, hypoglycaemia, diabetic ketoacidosis, previous myocardial infarction, stent thrombosis, known renal insufficiency, or previous coronary artery bypass operation.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: liraglutide<br>drug: liraglutide (Novo Nordisk, Bagsværd, Denmark) duration:7 days(from admission (primary percutaneous coronary intervention) to discharge) the intervention:once-daily subcutaneous liraglutide 0.6 mg for 2 days, then gradually increase the dosage, once-daily subcutaneous liraglutide 1.2 mg for 2 days ,once-daily subcutaneous liraglutide 1.8 mg for 3 days | Drug: liraglutide (Novo Nordisk, Bagsværd, Denmark)<br>* once-daily subcutaneous liraglutide 0.6 mg for 2 days, then gradually increase the dosage, once-daily subcutaneous liraglutide 1.2 mg for 2 days ,once-daily subcutaneous liraglutide 1.8 mg for 3 days<br>|
| Placebo Comparator: liraglutide placebo<br>drug:liraglutide placebo (Novo Nordisk) duration:7 days(from admission (primary percutaneous coronary intervention) to discharge) the intervention:once-daily subcutaneous liraglutide placebo 0.6 mg for 2 days, then gradually increase the dosage, once-daily subcutaneous liraglutide placebo 1.2 mg for 2 days ,once-daily subcutaneous liraglutide placebo 1.8 mg for 3 days | Drug: liraglutide placebo (Novo Nordisk)<br>* once-daily subcutaneous liraglutide placebo 0.6 mg for 2 days, then gradually increase the dosage, once-daily subcutaneous liraglutide placebo 1.2 mg for 2 days ,once-daily subcutaneous liraglutide placebo 1.8 mg for 3 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| the salvage index measured by cardiac magnetic resonance | The primary endpoint was the salvage index measured by cardiac magnetic resonance after 3 months. | 3 months after primary percutaneous coronary intervention | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| major adverse cardiovascular events (MACE) after 3 months | major adverse cardiovascular events (MACE) after 3 months: recurrent myocardial infarction, recurrent angina, revascularization, heart failure, cardiac death. treatment-emergent adverse events (TEAEs): hypoglycemia, nausea, acute pancreatitis | 3 months after Primary percutaneous coronary intervention | 
| final infarct size after 3 months |  | 3 months after Primary percutaneous coronary intervention | 
| the levels of high-sensitivity C-reactive protein (hsCRP) |  | 3 months after Primary percutaneous coronary intervention | 
| nitric oxide (NO) levels |  | 3 months after Primary percutaneous coronary intervention | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Reperfusion injury, Liraglutide