Prevention of Cardiovascular Disease Using a Single PolyPill in an Urban Population - Focus on Liver-Related Variables.

Study Overview
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Brief Summary
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The primary purpose of this study is to determine the effects of a fixed dose combination of valsartan, hydrochlorothiazide, atorvastatin and aspirin (PolyPill) on prevention of cardiovascular events in adults older than 50. Various liver-related variables will also be recorded which will allow studying the effects of PolyPill on the liver and the effect of liver diseases such as nonalcoholic steatohepatitis on cardiovascular events and the protective effect of PolyPill.

Detailed Description
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2400 subjects will be randomly selected from participants of the Golestan Cohort Study (GCS) who are living in Gonbad and are over 50 years old. These subjects will be randomized to either receive PolyPill or no treatment. Those agreeing to the study will undergo additional measurements (in addition to the baseline measurements performed in the GCS) including liver-related tests such as liver enzyme levels, abdominal ultrasonography and liver stiffness measurement. Some additional tests such as color doppler ultrasonography of carotid vessels will also be performed. Subjects in the PolyPill arm who have no contraindication for the components of the pill will receive a single daily dose of PolyPill for 5 years.

Official Title
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Fixed-dose Combination Therapy (PolyPill) in Prevention of Cardiovascular Disease in Middle-aged and Elderly Iranians - Focus on Liver-Related Variables.

Conditions
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Cardiovascular Diseases

Intervention / Treatment
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* Drug: Polypill


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: - Being enrolled in Golestan Cohort Study Exclusion Criteria: Debilitating disease causing inability to comply Contraindications to any of the components of PolyPill Not consenting to the study

Ages Eligible for Study
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Minimum Age: 50 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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Polypill<br>Single daily dose of PolyPill and 6-monthly visits | Drug: Polypill<br>* Polypill taken once daily for 5 years. Each pill contains acetylsalicylic acid 81 mg, atorvastatin 20 mg, hydrochlorothiazide 12.5 mg, valsartan 40 mg<br>* Other names: PolyPill 4-2;|
| No Intervention: Control<br>Only 6-monthly visits | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Major Cardiovascular Events | The first occurrence of hospitalization for acute coronary syndrome (non-fatal myocardial infarction and unstable angina), fatal myocardial infarction, sudden death, new-onset heart failure, coronary artery revascularization procedures and stroke (fatal or non-fatal). | 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Side effects | questionnaire | 5 years | 
| Changes in liver enzyme levels | AST, ALT | 5 years | 
| Changes in liver stiffness | As measured by fibroscan | 5 years | 
| Compliance | Pill count | 5 years | 
| Fat deposition | Visceral Adipose Tissue thickness (VAT), Subcutaneous Adipose Tissue thickness (SAT) and carotid intima-media thickness (IMT) | 5 years | 
| All-cause Mortality | Yearly follow-up | 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Atorvastatin, Aspirin, nonalcoholic steatohepatitis, nonalcoholic fatty liver disease, antihypertensive agents