Heart Outcomes Prevention Evaluation–3

Condition(s) targeted: Cardiovascular Disease; Stroke

Intervention: rosuvastatin calcium (10mg) (Drug); candesartan cilexetil (16mg) / hydrochlorothiazide (12.5mg) (Drug)

Phase: Phase 4

Status: Recruiting

Sponsored by: Population Health Research Institute

Official(s) and/or principal investigator(s):
Salim Yusuf, DPhil FRCPC, Principal Investigator, Affiliation: McMaster University
Eva Lonn, MD MSc FRCPC, Principal Investigator, Affiliation: McMaster University

Overall contact:
Jane Shannon, Email: hope3@cardio.on.ca

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 we 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. The trial will enroll 10,000 women 65 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 will be randomized to receive either the real study medications or placebo (dummy pills) and will be monitored for an average of 5 years. The rates of heart attacks, strokes, deaths and other cardiovascular complications will be compared between subjects receiving the real drugs and those on placebo. The study will include people from at least ten countries, will be monitored an international group of scientists and physicians and will be 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: Heart Outcomes Prevention Evaluation–3

Study design: Prevention, Randomized, Double-Blind, Placebo Control, Factorial Assignment, Safety/Efficacy Study

Primary outcome:

To evaluate the effects of lipid modification (LDL cholesterol lowering and HDL cholesterol raising) with rosuvastatin 10 mg daily on major CV events.

To evaluate the effects of blood pressure lowering with combined candesartan 16 mg/HCT 12.5 mg daily on major CV events.

To evaluate the impact of combined lipid modification with rosuvastatin 10 mg/day and blood pressure lowering with candesartan 16 mg/HCT 12.5 mg daily on major CV events.

Secondary outcome:

Total mortality

CV mortality

Coronary heart disease events

Cerebrovascular disease events

Heart failure

Revascularization procedures

Angina pectoris

Progression of renal disease

New diagnosis of diabetes

Minimum age: 55 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Women aged > 65 years and men > 55 years

- 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

- Severe 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

Jane Shannon, Email: hope3@cardio.on.ca

Hamilton General Hospital, Hamilton, Ontario L8L 2X2, Canada; Recruiting

Starting date: May 2007
Ending date: May 2013
Last updated: June 8, 2007