Heart Outcomes Prevention Evaluation-3 (HOPE-3)

• ClinicalTrials.gov Identifier: NCT00468923
• Recruitment Status: Completed
• First Posted: May 3, 2007
• Last Update Posted: October 25, 2017
• Sponsor: Population Health Research Institute
• Information provided by (Responsible Party): Salim Yusuf's office, Population Health Research Institute

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Cardiovascular Disease; Stroke	Drug: Candesartan/HCT; Drug: Rosuvastatin	Phase 4

Detailed Description:

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 12705 participants
• Allocation: Randomized
• Intervention Model: Factorial Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: Heart Outcomes Prevention Evaluation-3
• Study Start Date: May 2007
• Actual Primary Completion Date: December 2015
• Actual Study Completion Date: January 2016

Arms and Interventions

Arm	Intervention/treatment
Placebo Comparator: Rosuvastatin; Rosuvastatin 10 mg vs placebo	Drug: Rosuvastatin; Rosuvastatin 10 mg once daily
Placebo Comparator: Candesartan/HCT; Candesartan 16 mg/HCT 12.5 mg vs placebo	Drug: Candesartan/HCT; Candesartan 16 mg/HCT 12.5 once daily

Outcome Measures

Primary Outcome Measures :

1. The composite of; Cardiovascular death, non-fatal myocardial infarction, non-fatal stroke. [ Time Frame: Biannually ]
2. The composite of; cardiovascular death, resuscitated cardiac arrest, non-fatal myocardial infarction, non-fatal stroke, heart failure, arterial revascularizations [ Time Frame: Biannually ]

Secondary Outcome Measures :

1. Total mortality [ Time Frame: Biannually ]
2. The components of the co-primary endpoints [ Time Frame: Biannually ]

Other Outcome Measures:

1. Renal Dysfunction [ Time Frame: Biannually ]
2. Arterial revascularizations. [ Time Frame: Biannually ]
3. New diagnosis of diabetes. [ Time Frame: Biannually ]
4. All components of the co-primary and secondary outcomes [ Time Frame: Follow-up ]
5. Cognitive function [ Time Frame: Follow-up ]
6. Erectile dysfunction in men [ Time Frame: Biannually ]
7. Myopathy (defined as muscle aches or pains accompanied by CK rise >10ULN). [ Time Frame: Biannually ]
8. Rhabdomyolysis (defined as muscle pain and/or weakness associated with CK rise >10 ULN and evidence of acute renal dysfunction). [ Time Frame: Biannually ]
9. Hospital admissions and the reason for admission. [ Time Frame: Biannually ]
10. Cancer [ Time Frame: Biannually ]

Eligibility Criteria

• Ages Eligible for Study: 55 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

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

Contacts and Locations

Locations

Canada, Ontario

Hamilton General Hospital

Hamilton, Ontario, Canada, L8L 2X2

Sponsors and Collaborators

Population Health Research Institute

Investigators

• Principal Investigator: Salim Yusuf, DPhil FRCPC; McMaster University
• Principal Investigator: Eva Lonn, MD MSc FRCPC; McMaster University

More Information

Publications of Results:

Lonn EM, Bosch J, López-Jaramillo P, Zhu J, Liu L, Pais P, Diaz R, Xavier D, Sliwa K, Dans A, Avezum A, Piegas LS, Keltai K, Keltai M, Chazova I, Peters RJ, Held C, Yusoff K, Lewis BS, Jansky P, Parkhomenko A, Khunti K, Toff WD, Reid CM, Varigos J, Leiter LA, Molina DI, McKelvie R, Pogue J, Wilkinson J, Jung H, Dagenais G, Yusuf S; HOPE-3 Investigators. Blood-Pressure Lowering in Intermediate-Risk Persons without Cardiovascular Disease. N Engl J Med. 2016 May 26;374(21):2009-20. doi: 10.1056/NEJMoa1600175. Epub 2016 Apr 2.

Yusuf S, Bosch J, Dagenais G, Zhu J, Xavier D, Liu L, Pais P, López-Jaramillo P, Leiter LA, Dans A, Avezum A, Piegas LS, Parkhomenko A, Keltai K, Keltai M, Sliwa K, Peters RJ, Held C, Chazova I, Yusoff K, Lewis BS, Jansky P, Khunti K, Toff WD, Reid CM, Varigos J, Sanchez-Vallejo G, McKelvie R, Pogue J, Jung H, Gao P, Diaz R, Lonn E; HOPE-3 Investigators. Cholesterol Lowering in Intermediate-Risk Persons without Cardiovascular Disease. N Engl J Med. 2016 May 26;374(21):2021-31. doi: 10.1056/NEJMoa1600176. Epub 2016 Apr 2.

Yusuf S, Lonn E, Pais P, Bosch J, López-Jaramillo P, Zhu J, Xavier D, Avezum A, Leiter LA, Piegas LS, Parkhomenko A, Keltai M, Keltai K, Sliwa K, Chazova I, Peters RJ, Held C, Yusoff K, Lewis BS, Jansky P, Khunti K, Toff WD, Reid CM, Varigos J, Accini JL, McKelvie R, Pogue J, Jung H, Liu L, Diaz R, Dans A, Dagenais G; HOPE-3 Investigators. Blood-Pressure and Cholesterol Lowering in Persons without Cardiovascular Disease. N Engl J Med. 2016 May 26;374(21):2032-43. doi: 10.1056/NEJMoa1600177. Epub 2016 Apr 2. Erratum in: N Engl J Med. 2018 Oct 11;379(15):1486.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Khunti K, Jung H, Dans AL, Held C, Dagenais GR, Yusuf S, Lonn E. Statin Use in Primary Prevention: A Simple Trial-Based Approach Compared With Guideline-Recommended Risk Algorithms for Selection of Eligible Patients. Can J Cardiol. 2019 May;35(5):644-652. doi: 10.1016/j.cjca.2019.03.002. Epub 2019 Mar 19.

Bosch J, O'Donnell M, Swaminathan B, Lonn EM, Sharma M, Dagenais G, Diaz R, Khunti K, Lewis BS, Avezum A, Held C, Keltai M, Reid C, Toff WD, Dans A, Leiter LA, Sliwa K, Lee SF, Pogue JM, Hart R, Yusuf S; HOPE-3 Investigators. Effects of blood pressure and lipid lowering on cognition: Results from the HOPE-3 study. Neurology. 2019 Mar 26;92(13):e1435-e1446. doi: 10.1212/WNL.0000000000007174. Epub 2019 Feb 27.

Lamy A, Lonn E, Tong W, Swaminathan B, Jung H, Gafni A, Bosch J, Yusuf S. The cost implication of primary prevention in the HOPE 3 trial. Eur Heart J Qual Care Clin Outcomes. 2019 Jul 1;5(3):266-271. doi: 10.1093/ehjqcco/qcz001.

Lonn E, Bosch J, Pogue J, Avezum A, Chazova I, Dans A, Diaz R, Fodor GJ, Held C, Jansky P, Keltai M, Keltai K, Kunti K, Kim JH, Leiter L, Lewis B, Liu L, Lopez-Jaramillo P, Pais P, Parkhomenko A, Peters RJ, Piegas LS, Reid CM, Sliwa K, Toff WD, Varigos J, Xavier D, Yusoff K, Zhu J, Dagenais G, Yusuf S; HOPE-3 Investigators. Novel Approaches in Primary Cardiovascular Disease Prevention: The HOPE-3 Trial Rationale, Design, and Participants' Baseline Characteristics. Can J Cardiol. 2016 Mar;32(3):311-8. doi: 10.1016/j.cjca.2015.07.001. Epub 2015 Jul 8. Erratum in: Can J Cardiol. 2016 Dec;32(12 ):1573.

• Responsible Party: Salim Yusuf's office, Principal Investigator, Population Health Research Institute
• ClinicalTrials.gov Identifier: NCT00468923
• Other Study ID Numbers: HOPE-3
• First Posted: May 3, 2007
• Last Update Posted: October 25, 2017
• Last Verified: October 2017

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: Data will be shared with participants in the study April/May 2016

Keywords provided by Salim Yusuf's office, Population Health Research Institute:

Primary prevention; Cholesterol lowering; Blood pressure lowering; Cardiovascular disease prevention

Additional relevant MeSH terms:

Cardiovascular Diseases; Candesartan; Rosuvastatin Calcium; Anticholesteremic Agents; Hypolipidemic Agents; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Enzyme Inhibitors; Antihypertensive Agents; Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists