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

Dong-A University

Status and phase: Completed; Phase 4

Conditions: Myocardial Infarction

Treatments: Drug: usual dose of valsartan; Drug: high dose of valsartan

Study type: Interventional

Funder types: Other

Identifiers

NCT01340326

Donga 419

Details and patient eligibility

About

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.

Full 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.

Enrollment: 800 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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800 participants in 2 patient groups

Valsartan,high dose

Active Comparator group

Description:

high dose group (valsartan up to 320 mg/day)

Treatment:

Drug: high dose of valsartan

Valsartan, usual dose

Other group

Description:

usual dose group (valsartan 80 mg/day)

Treatment:

Drug: usual dose of valsartan