The Impact of Dose of Angiotensin-receptor Blocker Valsartan and Genetic Polymorphism on the Post-MI Ventricular Remodeling

Study Overview
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Brief Summary
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Angiotensin-converting enzyme inhibitors and angiotensin-receptor blocker valsartan ameliorate ventricular remodeling after myocardial infarction (MI). Although the amount of those drugs used in previous clinical trials, therefore recommended in practical guidelines is maximum clinical dose, it has not been clearly demonstrated whether the recommended dose is more efficacious compared to lower dose commonly used in clinical practice. In addition, the impact of genetic polymorphism in neurohormonal system on the pharmacological effect has not been explored in the setting of post-MI remodeling. Therefore, the investigators evaluate whether submaximal dose, which are lower than those in major pivotal trials but typically used in clinical practice, can offer similar benefit in post-MI ventricular remodeling.

Detailed Description
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A total of 1116 patients with left ventricular (LV) dysfunction following the first episode of acute ST-elevation MI are to be enrolled and randomized to maximal tolerable dose (up to 320 mg/day) or usual dose (80 mg/day) of valsartan for 12 months in 2:1 ratio. Echocardiographic analysis for quantifying post-MI ventricular remodeling and genotyping of blood samples are conducted in central core laboratory. Clinical assessment and laboratory test are performed at fixed times, and genetic polymorphisms of the patients are tested at the time of admission.

Conditions
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Myocardial Infarction

Intervention / Treatment
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* Drug: high dose of valsartan
* Drug: usual dose of valsartan


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Both gender Age > 18 First episode of acute ST-elevation MI An echocardiographic left ventricular ejection fraction less than 50 % Patients who provide written informed consent Exclusion Criteria: Contraindications for use of angiotensin receptor blockers (ARBs)(hypersensitivity, pregnancy, bilateral renal artery stenosis) Urgent need for revascularization procedure Severe heart failure (need for intravenous inotropic support) Persistent (> 1 hour) severe hypotension (systolic blood pressure < 90 mmHg) Refractory or potentially lethal arrhythmias Hemodynamically significant right ventricular infarction Primary valvular diseases Congenital heart disease Idiopathic hypertrophic cardiomyopathy Concomitant inflammatory cardiopathy Significant hepatic dysfunction Significant renal dysfunction Anemia (hemoglobin < 10 mg/mL) Psychiatric disorders, alcohol or durg abuse Any concomitant disease that might interfere with drug evaluation (especially if life expectancy is less than 1 year) Participation in any other pharmacological study within 2 months Refusal or inability to provide informed consent

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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Valsartan,high dose<br>high dose group (valsartan up to 320 mg/day) | Drug: high dose of valsartan<br>* comparison of different dosages of drug<br>|
| Other: Valsartan, usual dose<br>usual dose group (valsartan 80 mg/day) | Drug: usual dose of valsartan<br>* comparison of different dosages of drug<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in the left ventricular volume index from baseline to follow-up | We measured a left ventriular volume index by echocardiography. | at 24hrs, 1month, and 12months after myocardial infarction | 
| left ventricular volume index |  | at 12months after myocardial infarction | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| clinical events | Clinical events were defined as all cause death and hospitalization due to cardiovascular problems. | during 12 months follow up | 
| clinical events |  | at 12 months after myocardial infarction | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Post myocardial infarction ventricular remodeling, valsartan