Prevention of Cardiovascular Disease in Middle-aged and Elderly Iranians Using a Single PolyPill

Study Overview
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Brief Summary
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The purpose of this study is to determine the effects of PolyPill tablet (a fixed dose combination of two anti-hypertensive medications, atorvastatin and aspirin) on primary and secondary prevention of cardiovascular disease in Iranian adults older than 50.

Detailed Description
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Cardiovascular diseases (myocardial infarction and stroke) are the most common cause of death and disability in Iran and account for nearly half of all-cause mortality in Iranians. Therefore, prevention of cardiovascular diseases is a top priority in countries with limited health system budgets such as Iran. Eighty seven to hundred percent of patients dying from Coronary Heart Disease (CHD) have at least one risk factor for cardiovascular diseases. Therefore, risk factor modification in middle-aged and old individuals might prevent death and is a main priority. Combination drug therapy has been proposed as a cost-effective measure to reduce modifiable risk factors for cardiovascular disease in aged people. It has been showed that combination drug therapy can potentially decrease ischemic heart events and strokes by 88 and 80 percent, respectively. The purpose of this study is to determine the effects of PolyPill tablet (a fixed dose combination of two anti-hypertensive medications, atorvastatin and aspirin) on primary and secondary prevention of cardiovascular disease in Iranian adults older than 50. This is a study on subjects older than 50 enrolled in the Golestan Cohort Study. The study is designed as a pragmatic cluster randomized trial. The study comprises three arms as follows: 4234 randomly selected participants receive PolyPill tablets once daily and Minimal care (which consists of direct education and pamphlet on cardiovascular risk reduction, biannual follow-ups and BP measurements). 4177 randomly selected participants receive only Minimal care as described above. Include remaining 24000 participants of rural participants of Golestan cohort, aged 50 and higher who receive the basic primary health care provided by the local physicians and Community Health Workers for the whole participants of Golestan Cohort study consistent with the current Iranian Health Care System guidelines. A random sample of 4395 subjects from this usual care arm were selected from this group as the third arm of the study and outcome ascertainment will be performed for this sample and will be used in the secondary comparison. Arms #1 and #2 are compared via a 2-armed open-labeled cluster Randomized Controlled Trial. Comparisons between arm #3 and the other 2 arms are also performed. Endpoints include major cardiovascular events (death and hospitalization)

Official Title
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Fixed-dose Combination Therapy (PolyPill) in Primary and Secondary Prevention of Cardiovascular Disease in Middle-aged and Elderly Iranians

Conditions
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Cardiovascular Diseases

Intervention / Treatment
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* Drug: PolyPill
* Other: Minimal care


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 50-79 years old Enrollment in the Golestan Cohort Study Exclusion Criteria: Hypersensitivity to any of PolyPill components: Hypersensitivity to Non-steroidal anti-inflammatory agents Hypersensitivity to statins Hypersensitivity to hydrochlorothiazide or sulfonamides Hypersensitivity to enalapril and valsartan Past medical history of angioedema Medical history of GI bleeding or peptic ulcer in the last 3 months Pregnancy or lactation Bleeding disorders such as hemophilia Receiving anticoagulation therapy Alcohol consumption greater than 40gr/week Advanced liver disease Uncontrolled seizures Asthma with any of the following criteria present: Daily symptoms Asthmatic attacks waking the patient from sleep more than once a week History of nasal polyps Aspirin sensitive asthma Presence of rhinitis symptoms not due to infection Past medical history of gout Serum creatinine values above 2 mg/dL or a Glomerular Filtration Rate (GFR) below 30 mL/min Hemoglobin concentrations below 11 g/dL for males and 10 g/dL for females BP < 90/60 Debilitating medical/mental disorders affecting medication compliance (including psychosis, disabilities, and blindness) Past medical history of stroke

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 79 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: PolyPill<br>PolyPill once daily and Minimal Care | Drug: PolyPill<br>* A combination tablet containing Aspirin 81 mg, enalapril 5 mg (or valsartan 40 mg), atorvastatin 20 mg and hydrochlorothiazide 12.5 mg taken once daily<br>* Other names: PolyPill 4-2;Other: Minimal care<br>* Health education pamphlet on reducing cardiovascular risk factors, direct education on reducing cardiovascular risk factors provided by the study physician and the Community Health Worker, biannual follow-up and BP measurement<br>|
| Active Comparator: Minimal care<br>Minimal care. | Other: Minimal care<br>* Health education pamphlet on reducing cardiovascular risk factors, direct education on reducing cardiovascular risk factors provided by the study physician and the Community Health Worker, biannual follow-up and BP measurement<br>|
| No Intervention: Usual care<br>Basic primary health care provided by the local physicians and Community Health Workers consistent with the current Iranian Health Care System guidelines. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to first major cardiovascular event | Major cardiovascular events are defined as: Major coronary events include: sudden cardiac death, myocardial infarction, a diagnosis of angina, revascularization procedure Cerebrovascular accidents (CVA) including transient ischemic attacks (TIA) Hospitalization because of cardiovascular disease | 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Blood pressure | Changes in blood pressure after 5 years | 5 years | 
| Fasting blood sugar, total cholesterol, HDL-C and LDL-C | Changes in fasting blood sugar and lipid profile after 5 years | 5 years | 
| Number of Subjects Developing Adverse Events | Number of participants who experience adverse effects to the PolyPill tablet leading to discontinuation. | 5 years | 
| Compliance | Compliance is measured by pill-count in participants of the intervention arm as percent pills taken. | 5 years | 
| Rate of major cardiovascular events | Number of major cardiovascular events (as described above) during 5 years | 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cardiovascular Diseases, Drug Combinations, prevention and control, Aspirin, Antihypertensive Agents, Antilipemic Agents