Heart Outcomes Prevention Evaluation-3

NCT00468923 | Completed Phase 4 DMC

• 1 other identifier: HOPE-3
• Study Type: interventional
• Target: 12,705
• Locations: 1 country
• Sites: 1

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.

Conditions

Cardiovascular Disease; Stroke

Keywords

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

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (2)

• Total mortality

  Biannually

• The components of the co-primary endpoints

  Biannually

Other Outcomes (10)

• Renal Dysfunction

  Biannually

• Arterial revascularizations.

  Biannually

• New diagnosis of diabetes.

  Biannually

Study Arms (2)

Rosuvastatin

PLACEBO COMPARATOR

Rosuvastatin 10 mg vs placebo

Drug: Rosuvastatin

Candesartan/HCT

PLACEBO COMPARATOR

Candesartan 16 mg/HCT 12.5 mg vs placebo

Drug: Candesartan/HCT

Interventions

Candesartan/HCT DRUG

Candesartan 16 mg/HCT 12.5 once daily

Candesartan/HCT

Rosuvastatin DRUG

Rosuvastatin 10 mg once daily

Rosuvastatin

Eligibility Criteria

• Age: 55 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Population Health Research Institute: lead

Study Sites (1)

Hamilton General Hospital

Hamilton, Ontario, L8L 2X2, Canada

Location

Related Publications (10)

• Lonn EM, Bosch J, Lopez-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.

  PMID: 27041480 RESULT

• Yusuf S, Bosch J, Dagenais G, Zhu J, Xavier D, Liu L, Pais P, Lopez-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.

  PMID: 27040132 RESULT

• Yusuf S, Lonn E, Pais P, Bosch J, Lopez-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.

  PMID: 27039945 RESULT

• Dagenais GR, Pais P, Gao P, Roshandel G, Malekzadeh R, Joseph P, Yusuf S. Fixed dose combination therapies in primary cardiovascular disease prevention in different groups: an individual participant meta-analysis. Heart. 2023 Aug 24;109(18):1372-1379. doi: 10.1136/heartjnl-2022-322278.

  PMID: 37258095 DERIVED

• Bosch J, Lonn EM, Dagenais GR, Gao P, Lopez-Jaramillo P, Zhu J, Pais P, Avezum A, Sliwa K, Chazova IE, Peters RJG, Held C, Yusoff K, Lewis BS, Toff WD, Khunti K, Reid CM, Leiter LA, Yusuf S, Hart RG. Antihypertensives and Statin Therapy for Primary Stroke Prevention: A Secondary Analysis of the HOPE-3 Trial. Stroke. 2021 Aug;52(8):2494-2501. doi: 10.1161/STROKEAHA.120.030790. Epub 2021 May 14.

  PMID: 33985364 DERIVED

• Bosch J, Lonn EM, Jung H, Zhu J, Liu L, Lopez-Jaramillo P, Pais P, Xavier D, Diaz R, Dagenais G, Dans A, Avezum A, Piegas LS, Parkhomenko A, Keltai K, Keltai M, Sliwa K, Held C, Peters RJG, Lewis BS, Jansky P, Yusoff K, Khunti K, Toff WD, Reid CM, Varigos J, Joseph P, Leiter LA, Yusuf S. Lowering cholesterol, blood pressure, or both to prevent cardiovascular events: results of 8.7 years of follow-up of Heart Outcomes Evaluation Prevention (HOPE)-3 study participants. Eur Heart J. 2021 Aug 17;42(31):2995-3007. doi: 10.1093/eurheartj/ehab225.

  PMID: 33963372 DERIVED

• 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.

  PMID: 31030865 DERIVED

• 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.

  PMID: 30814321 DERIVED

• 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.

  PMID: 30657891 DERIVED

• 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.

  PMID: 26481083 DERIVED

MeSH Terms

Conditions

Cardiovascular Diseases; Stroke

Interventions

Rosuvastatin Calcium

Condition Hierarchy (Ancestors)

Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases

Intervention Hierarchy (Ancestors)

Sulfonamides; Amides; Organic Chemicals; Fluorobenzenes; Hydrocarbons, Fluorinated; Hydrocarbons, Halogenated; Hydrocarbons; Sulfones; Sulfur Compounds; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Salim Yusuf, DPhil FRCPC

  McMaster University

  PRINCIPAL INVESTIGATOR

• Eva Lonn, MD MSc FRCPC

  McMaster University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: May 2, 2007
• First Posted: May 3, 2007
• Study Start: May 1, 2007
• Primary Completion: December 1, 2015
• Study Completion: January 1, 2016
• Last Updated: October 25, 2017

Record last verified: 2017-10

Data Sharing

• IPD Sharing: Will share

Locations

CA (1)