Heart Outcomes Prevention Evaluation-3 - Full Text View

Purpose

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	Intervention	Phase
Cardiovascular Disease Stroke	Drug: Candesartan/HCT Drug: Rosuvastatin	Phase 4


Study Type:	Interventional
Study Design:	Allocation: Randomized Intervention Model: Factorial Assignment Masking: Participant, Care Provider, Investigator, Outcomes Assessor Primary Purpose: Prevention
Official Title:	Heart Outcomes Prevention Evaluation-3

Resource links provided by NLM:

Drug Information available for: Candesartan Candesartan cilexetil Rosuvastatin calcium Rosuvastatin

U.S. FDA Resources

Further study details as provided by Salim Yusuf's office, Population Health Research Institute:

Primary Outcome Measures:

The composite of; Cardiovascular death, non-fatal myocardial infarction, non-fatal stroke. [ Time Frame: Biannually ]
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:

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

Other Outcome Measures:

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


Enrollment:	12705
Study Start Date:	May 2007
Study Completion Date:	January 2016
Primary Completion Date:	December 2015 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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

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.

Eligibility


Ages Eligible for Study:	55 Years and older (Adult, Senior)
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

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00468923

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

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.

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.


Responsible Party:	Salim Yusuf's office, Principal Investigator, Population Health Research Institute
ClinicalTrials.gov Identifier:	NCT00468923 History of Changes
Other Study ID Numbers:	HOPE-3
Study First Received:	May 2, 2007
Last Updated:	February 8, 2017
Individual Participant Data
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 Rosuvastatin Calcium Candesartan Candesartan cilexetil Hydroxymethylglutaryl-CoA Reductase Inhibitors Anticholesteremic Agents Hypolipidemic Agents	Antimetabolites Molecular Mechanisms of Pharmacological Action Enzyme Inhibitors Lipid Regulating Agents Antihypertensive Agents Angiotensin II Type 1 Receptor Blockers Angiotensin Receptor Antagonists

ClinicalTrials.gov processed this record on June 23, 2017

Heart Outcomes Prevention Evaluation-3 (HOPE-3)