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