Novel Approaches in Primary Cardiovascular Disease Prevention: The HOPE-3 Trial Rationale, Design, and Participants' Baseline Characteristics.
BACKGROUND
Cholesterol and blood pressure (BP) can be effectively and safely lowered with statin drugs and BP-lowering drugs, reducing major cardiovascular (CV) events by 20%-30% within 5 years in high-risk individuals. However, there are limited data in lower-risk populations. The Heart Outcomes Prevention Evaluation-3 (HOPE-3) trial is evaluating whether cholesterol lowering with a statin drug, BP lowering with low doses of 2 antihypertensive agents, and their combination safely reduce major CV events in individuals at intermediate risk who have had no previous vascular events and have average cholesterol and BP levels.


METHODS
A total of 12,705 women 65 years or older and men 55 years or older with at least 1 CV risk factor, no known CV disease, and without any clear indication or contraindication to the study drugs were randomized to rosuvastatin 10 mg/d or placebo and to candesartan/hydrochlorothiazide 16/12.5 mg/d or placebo (2 × 2 factorial design) and will be followed for a mean of 5.8 years. The coprimary study outcomes are the composite of CV death, nonfatal myocardial infarction (MI), and nonfatal stroke and the composite of CV death, nonfatal MI, nonfatal stroke, resuscitated cardiac arrest, heart failure, and arterial revascularization.


RESULTS
Participants were recruited from 21 countries in North America, South America, Europe, Asia, and Australia. Mean age at randomization was 66 years and 46% were women.


CONCLUSIONS
The HOPE-3 trial will provide new information on cholesterol and BP lowering in intermediate-risk populations with average cholesterol and BP levels and is expected to inform approaches to primary prevention worldwide (HOPE-3 ClinicalTrials.gov NCT00468923).
Department of Medicine, McMaster University, Hamilton, Ontario, Canada; Population Health Research Institute, Hamilton Health Sciences and McMaster University, Hamilton, Ontario, Canada. Electronic address: eva.lonn@phri.ca.
Eva
E
Lonn
Population Health Research Institute, Hamilton Health Sciences and McMaster University, Hamilton, Ontario, Canada.
Jackie
J
Bosch
Population Health Research Institute, Hamilton Health Sciences and McMaster University, Hamilton, Ontario, Canada.
Janice
J
Pogue
Dante Pazzanese Institute of Cardiology, São Paulo, Brazil.
Alvaro
A
Avezum
Russian Cardiology Research Complex, Moscow, Russian Federation.
Irina
I
Chazova
College of Medicine of the University of the Philippines, Manula, Philippines.
Antonio
A
Dans
Fundacion ECLA, Rosario, Argentina.
Rafael
R
Diaz
University of Ottawa Heart Institute, Ottawa, Ontario, Canada.
George J
GJ
Fodor
Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
Claes
C
Held
University Hospital Motol, Prague, Czech Republic.
Petr
P
Jansky
Hungarian Institute of Cardiology, Semmelweis University, Budapest, Hungary.
Matyas
M
Keltai
Hungarian Institute of Cardiology, Semmelweis University, Budapest, Hungary.
Katalin
K
Keltai
Diabetes Research Centre, University of Leicester, Leicester, United Kingdom.
Kamlesh
K
Kunti
St. Paul's Hospital, The Catholic University of Korea, Seoul, Korea.
Jae-Hyung
JH
Kim
Li Ka Shing Knowledge Institute and Keenan Research Centre for Biomedical Science, St. Michael's Hospital, University of Toronto, Toronto, Ontario, Canada.
Lawrence
L
Leiter
Lady Davis Carmel Medical Center and the Ruth and Bruce Rappaport School of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.
Basil
B
Lewis
Fu Wai Hospital, Chinese Academy of Medical Sciences, Beijing, China.
Lisheng
L
Liu
Fundacion Oftalmolgica de Santander (FOSCAL) and Instituto Masira, Medical School, Universidad de Santander, Bucaramanga, Colombia.
Patricio
P
Lopez-Jaramillo
Division of Clinical Research and Training, St. John's Research Institute, Bangalore, India.
Prem
P
Pais
Ukranian Strazhesko Institute of Cardiology, Kiev, Ukraine.
Alexandr
A
Parkhomenko
Department of Cardiology, Academic Medical Center, Amsterdam, The Netherlands.
Ron J G
RJ
Peters
Hospital do Coração, São Paulo, Brazil.
Leopoldo S
LS
Piegas
Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Australia.
Christopher M
CM
Reid
Hatter Institute for Cardiovascular Research in Africa, Department of Medicine, University of Cape Town and Soweto Cardiovascular Research Group, University of the Witwatersrand, Johannesburg, South Africa.
Karen
K
Sliwa
Department of Cardiovascular Sciences, University of Leicester and Leicester NIHR Biomedical Research Unit in Cardiovascular Disease, Glenfield Hospital, Leicester, United Kingdom.
William D
WD
Toff
Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Australia.
John
J
Varigos
Division of Clinical Research and Training, St. John's Research Institute, Bangalore, India.
Denis
D
Xavier
Universiti Teknologi MARA, Selangor, Malaysia.
Khalid
K
Yusoff
Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Jun
J
Zhu
Institut Universitaire de Cardiologie et Pneumologie de Québec, Université Laval, Québec, Canada.
Gilles
G
Dagenais
Department of Medicine, McMaster University, Hamilton, Ontario, Canada; Population Health Research Institute, Hamilton Health Sciences and McMaster University, Hamilton, Ontario, Canada.
Salim
S
Yusuf
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D047228:Angiotensin II Type 1 Receptor Blockers; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D008078:Cholesterol, LDL; D004232:Diuretics; D013777:Tetrazoles; D006852:Hydrochlorothiazide; D000068718:Rosuvastatin Calcium; C081643:candesartan