Heart Outcomes Prevention Evaluation-3

Study Overview
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Brief Summary
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Heart disease and stroke are major causes of death and disability worldwide and are largely preventable. Cholesterol and blood pressure are major cardiovascular risk factors. Previous studies have shown that certain drugs can effectively and safely lower cholesterol and blood pressure and prevent heart attacks and strokes. Such studies have been conducted primarily in people who had already sustained a heart attack or a stroke, or in people with high cholesterol and blood pressure levels. However, most heart attacks and strokes occur in people with average (normal) cholesterol and blood pressure. Therefore, in the HOPE-3 trial the investigators will evaluate whether a cholesterol lowering drug, rosuvastatin, and a combination blood pressure lowering pill, candesartan/hydrochlorothiazide, used alone or together can reduce the risk of heart attacks, stroke and their sequelae in people without known heart disease and at average risk.

Detailed Description
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The trial has randomized 12,705 women 60 years or older and men 55 years or older without known heart disease or prior stroke and without a clear indication or contraindication to any of the study medications. Eligible and consenting individuals were randomized to receive either active study medications or placebo (dummy pills) and will be monitored for an average of 5.7 years. The rates of heart attacks, strokes, deaths and other cardiovascular events will be compared between subjects receiving the active drugs and those on placebo. The study included people from 21 countries, which were monitored by an international group of scientists and physicians. The study was coordinated by the Population Health Research Institute at McMaster University. The study is expected to demonstrate that combined lipid lowering and blood pressure lowering will substantially lower the risk for cardiovascular diseases and may substantially change our approach to cardiovascular prevention.

Official Title
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Heart Outcomes Prevention Evaluation-3

Conditions
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Cardiovascular Disease, Stroke

Intervention / Treatment
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* Drug: Candesartan/HCT
* Drug: Rosuvastatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Women aged > 60 years and men > 55 years At least one additional CV risk factor including: Waist/hip ratio ≥ 0.90 in men and ≥ 0.85 in women; History of current or recent smoking (regular tobacco use within 5 years) Low HDL cholesterol Dysglycemia Renal dysfunction Family history of premature CHD in first degree relatives Exclusion Criteria: Documented clinically manifest atherothrombotic CVD Clear indication or contraindication for statin and/or ARB or ACE inhibitor and/or thiazide diuretic therapy Symptomatic hypotension Chronic liver disease Inflammatory muscle disease Renal impairment Concurrent treatment with cyclosporine or a condition likely to result in organ transplantation and the need for cyclosporine Concurrent treatment with a statin, fibrate, angiotensin receptor blocker, ACE inhibitor, or a thiazide diuretic Other serious medical illness likely to interfere with study participation or with the ability to complete the trial Significant psychiatric illness, senility, dementia, alcohol or substance abuse, which could impair the ability to provide informed consent and to adhere to the trial procedures Concurrent use of an experimental pharmacological agent

Ages Eligible for Study
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Minimum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Rosuvastatin<br>Rosuvastatin 10 mg vs placebo | Drug: Rosuvastatin<br>* Rosuvastatin 10 mg once daily<br>|
| Placebo Comparator: Candesartan/HCT<br>Candesartan 16 mg/HCT 12.5 mg vs placebo | Drug: Candesartan/HCT<br>* Candesartan 16 mg/HCT 12.5 once daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The composite of; Cardiovascular death, non-fatal myocardial infarction, non-fatal stroke. |  | Biannually | 
| The composite of; cardiovascular death, resuscitated cardiac arrest, non-fatal myocardial infarction, non-fatal stroke, heart failure, arterial revascularizations |  | Biannually | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total mortality |  | Biannually | 
| The components of the co-primary endpoints |  | Biannually | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Primary prevention, Cholesterol lowering, Blood pressure lowering, Cardiovascular disease prevention