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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Rosuvastatin | Placebo Comparator | Rosuvastatin 10 mg vs placebo |
|
| Candesartan/HCT | Placebo Comparator | Candesartan 16 mg/HCT 12.5 mg vs placebo |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Candesartan/HCT | Drug | Candesartan 16 mg/HCT 12.5 once daily |
| |
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Total mortality | Biannually | |
| The components of the co-primary endpoints | Biannually |
| Measure | Description | Time Frame |
|---|---|---|
| Renal Dysfunction | Biannually | |
| Arterial revascularizations. | Biannually | |
| New diagnosis of diabetes. |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Salim Yusuf, DPhil FRCPC | McMaster University | Principal Investigator |
| Eva Lonn, MD MSc FRCPC | McMaster University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Hamilton General Hospital | Hamilton | Ontario | L8L 2X2 | Canada |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 27041480 | Result | 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. | |
| 27040132 |
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Data will be shared with participants in the study April/May 2016
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| ID | Term |
|---|---|
| D002318 | Cardiovascular Diseases |
| D020521 | Stroke |
| ID | Term |
|---|---|
| D002561 | Cerebrovascular Disorders |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
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| ID | Term |
|---|---|
| D000068718 | Rosuvastatin Calcium |
| ID | Term |
|---|---|
| D013449 | Sulfonamides |
| D000577 | Amides |
| D009930 | Organic Chemicals |
| D005464 | Fluorobenzenes |
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| Rosuvastatin |
| Drug |
Rosuvastatin 10 mg once daily |
|
| Biannually |
| All components of the co-primary and secondary outcomes | Follow-up |
| Cognitive function | Follow-up |
| Erectile dysfunction in men | Biannually |
| Myopathy (defined as muscle aches or pains accompanied by CK rise >10ULN). | Biannually |
| Rhabdomyolysis (defined as muscle pain and/or weakness associated with CK rise >10 ULN and evidence of acute renal dysfunction). | Biannually |
| Hospital admissions and the reason for admission. | Biannually |
| Cancer | Biannually |
| 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. |
| 27039945 | 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. |
| 37258095 | Derived | 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. |
| 33985364 | 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. |
| 33963372 | 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. |
| 31030865 | 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. |
| 30814321 | 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. |
| 30657891 | 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. |
| 26481083 | 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. |
| D014652 | Vascular Diseases |
| D006845 |
| Hydrocarbons, Fluorinated |
| D006846 | Hydrocarbons, Halogenated |
| D006838 | Hydrocarbons |
| D013450 | Sulfones |
| D013457 | Sulfur Compounds |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |