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

Condition(s) targeted: Myocardial Infarction

Intervention: high dose of valsartan (Drug); usual dose of valsartan (Drug)

Phase: Phase 4

Status: Recruiting

Sponsored by: Dong-A University

Overall contact:
Young Dae Kim, MD, Phone: 82-51-240-5621, Email: kimyd@dau.ac.kr

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.

Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Subject), Primary Purpose: Treatment

Primary outcome:

Change in the left ventricular volume index from baseline to follow-up

left ventricular volume index

Secondary outcome:

clinical events

clinical events

Detailed description: 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.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

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

Young Dae Kim, MD, Phone: 82-51-240-5621, Email: kimyd@dau.ac.kr

Department of Internal Medicine,Dong-A University College of Medicine, Busan, Korea, Republic of; Recruiting
Kyung IL Park, MD, Phone: 82-51-240-2733, Email: sotier@dau.ac.kr
Young Rak Cho, MD, Phone: 82-10-8553-0723, Email: progress2090@gmail.com

Starting date: November 2007
Last updated: April 18, 2012