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

Phase 4
Completed
Conditions
Myocardial Infarction
Interventions
Drug: high dose of valsartan
Drug: usual dose of valsartan
Registration Number
NCT01340326
Lead Sponsor
Dong-A University
Brief Summary

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

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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
800
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Valsartan,high dosehigh dose of valsartanhigh dose group (valsartan up to 320 mg/day)
Valsartan, usual doseusual dose of valsartanusual dose group (valsartan 80 mg/day)
Primary Outcome Measures
NameTimeMethod
Change in the left ventricular volume index from baseline to follow-upat 24hrs, 1month, and 12months after myocardial infarction

We measured a left ventriular volume index by echocardiography.

left ventricular volume indexat 12months after myocardial infarction
Secondary Outcome Measures
NameTimeMethod
clinical eventsat 12 months after myocardial infarction

Trial Locations

Locations (1)

Department of Internal Medicine,Dong-A University College of Medicine

🇰🇷

Busan, Korea, Republic of

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