Prevention of Cardiovascular Disease With Polypill Among Pars Cohort Participants

Study Overview
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Brief Summary
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The purpose of this study is to determine the effects of a fixed dose combination of enalapril (or valsartan), with hydrochlorthiazide, atorvastatin and acetylsalicylic acid (PolyPill) on primary and secondary prevention of cardiovascular disease in participants of Pars Cohort of Iran.

Detailed Description
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Cardiovascular diseases (CVDs) are the most common causes 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 CVDs have at least one risk factor for cardiovascular diseases. Therefore, risk factor modification 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. It has been showed that combination drug therapy can potentially decrease ischemic heart events and strokes by 88 and 80 percent, respectively. The study is designed as a pragmatic cluster randomized controlled trial. The purpose of this study is to determine the effects of a fixed dose combination of either enalapril or valsartan, with hydrochlorthiazide, atorvastatin and acetylsalicylic acid (PolyPill) on primary and secondary prevention of cardiovascular disease in Iranian adults older than 50. Two formulations of Polypill tablets were used. The first formulation (Polypill-E) contained enalapril 5 mg. If participants developed cough, they were switched by a trained physician to Polypill-V, containing valsartan 40 mg instead of enalapril. The investigators have previously tested the same combination in a different setting in Golestan, Northeast of Iran. The results of the study were published in the Lancet. The current study enrolls participants of Pars Cohort running in Fars province, southern Iran, aged above 50. A total of 4415 participants (91 clusters) were recruited following inclusion and exclusion criteria. The study comprises two arms as follows: 2200 randomly selected participants receive PolyPill tablets once daily and minimal care (which consists of direct education and pamphlet on cardiovascular risk reduction). 2215 randomly selected participants receive only minimal care as described above. Endpoints include major cardiovascular events (MCVE).

Official Title
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Effectiveness of Polypill for Primary Prevention of Cardiovascular Disease (PolyPars): Study Design and Rationale for a Pragmatic Cluster Randomized Controlled Trial

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: 50-79 years old Enrollment in the Pars Cohort Study Exclusion Criteria: Not consenting to participate in the study 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 regular 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 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 mmHg Debilitating medical/mental disorders affecting 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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PolyPill<br>Single daily dose of PolyPill and minimal care. | Drug: PolyPill<br>* After the baseline enrollment and excluding non-eligible participants, we randomized villages to Polypill and control arms. Follow-ups are scheduled for 1, 3, and 6 months after the initial enrollment in the Polypill arm and every six months thereafter. For the minimal care arm, the follow-ups are arranged every six months.<br>* Other names: PolyPill-E, Polypill-V;|
| No Intervention: Control<br>Only minimal care | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Major Cardiovascular Events (MCVE) | the first occurrence of acute coronary syndrome (non-fatal myocardial infarction and unstable angina), fatal myocardial infarction, sudden cardiac death, new-onset heart failure, coronary artery revascularization procedures, transient ischemic attack, cerebrovascular accidents (fatal or non-fatal), and hospitalization due to any of the mentioned conditions. | 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| Non cardiovascular mortality | Any death other than those due to CVDs during 5 years | 5 years | 
| Level of fasting blood sugar (mg/dL) | Changes in fasting blood sugar after 5 years | 5 years | 
| Level of blood pressure (mmHg) | Changes in blood pressure after 5 years | 5 years | 
| Level of total cholesterol (mg/dL) | Changes in total cholesterol after 5 years | 5 years | 
| Level of HDL (mg/dL) | Changes in HDL after 5 years | 5 years | 
| Level of LDL (mg/dL) | Changes in LDL after 5 years | 5 years | 
| Level of triglycerides (mg/dL) | Changes in triglycerides after 5 years | 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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fixed-dose combination therapy, Polypill, Prevention, Cardiovascular diseases