Abstract
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).
Résumé
Introduction
Il est possible de faire baisser efficacement et en toute sécurité le cholestérol
et la pression artérielle (PA) avec les statines et les antihypertenseurs tout en
réduisant de 20 à 30 % les manifestations cardiovasculaires majeures en l’espace de
cinq ans chez les personnes à risque élevé. Les données obtenues dans les populations
exposées à un risque plus faible sont néanmoins limitées. L’essai HOPE-3 (Heart Outcomes Prevention Evaluation-3) tâche de déterminer si l’abaissement du cholestérol à l’aide d’une statine, l’abaissement
de la pression artérielle à l’aide de deux agents antihypertenseurs administrés à
raison d’une faible dose et leur association permettent de réduire en toute sécurité
les manifestations cardiovasculaires majeures chez les personnes exposées à un risque
intermédiaire qui n’ont pas d’antécédents d’événements vasculaires et dont le taux
de cholestérol et la PA se situent dans la moyenne.
Méthodes
Au total, 12 705 femmes et hommes, les unes âgées de 65 ans et plus et les autres
de 55 ans et plus, qui présentent au moins un facteur de risque cardiovasculaire et
qui n’ont pas de maladie cardiovasculaire connue ni aucune indication ou contre-indication
claires aux médicaments à l’étude, ont été répartis aléatoirement pour recevoir de
la rosuvastatine à raison de 10 mg par jour ou un placebo et l’association candésartan/hydrochlorothiazide
à raison de 16/12,5 mg par jour ou un placebo (plan factoriel 2 × 2). Ces patients
seront suivis pendant une moyenne de 5,8 ans. Les principaux paramètres d’évaluation
de l’étude combinent le décès d’origine cardiovasculaire, l’infarctus du myocarde
non mortel et l’AVC non mortel d’une part, et le décès d’origine cardiovasculaire,
l’infarctus du myocarde non mortel, l’AVC non mortel, la réanimation après arrêt cardiaque,
l’insuffisance cardiaque et la revascularisation artérielle d’autre part.
Résultats
Les participants ont été recrutés dans 21 pays situés en Amérique du Nord, en Amérique
du Sud, en Europe, en Asie et en Australie. L’âge moyen au moment de la répartition
aléatoire était de 66 ans, et 46 % des sujets étaient des femmes.
Conclusions
L’essai HOPE-3 fournira de nouveaux renseignements sur l’abaissement du taux de cholestérol
et de la PA dans des populations exposées à un risque intermédiaire dont le taux de
cholestérol et la PA se situent dans la moyenne. Il devrait également fournir des
données à l’appui des stratégies de prévention primaire mises en place partout dans
le monde (HOPE-3 ClinicalTrials.gov NCT00468923).
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Canadian Journal of CardiologyAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
World Health Organization. The top 10 causes of death. Fact sheet N°310. Updated May 2014. Available at: http://www.who.int/mediacentre/factsheets/fs310/en/. Accessed August 31, 2015.
- Prediction of lifetime risk for cardiovascular disease by risk factor burden at 50 years of age.Circulation. 2006; 113: 791-798
- Strategy of prevention: lessons from cardiovascular disease.BMJ. 1981; 282: 1847-1851
- Trends in the prevalence of low risk factor burden for cardiovascular disease among United States adults.Circulation. 2009; 120: 1181-1188
- Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): case-control study.Lancet. 2004; 364: 937-952
- Prevalence, awareness, treatment, and control of hypertension in rural and urban communities in high-, middle-, and low-income countries.JAMA. 2013; 310: 959-968
- Proportion and risk indicators of nonadherence to statin therapy: a meta-analysis.Can J Cardiol. 2012; 28: 574-580
- Adherence to drugs that prevent cardiovascular disease: meta-analysis on 376,162 patients.Am J Med. 2012; 125: 882-887
- Adherence to cardiovascular therapy: a meta-analysis of prevalence and clinical consequences.Eur Heart J. 2013; 34: 2940-2948
- Multiple risk factor interventions for primary prevention of coronary heart disease.Cochrane Database Syst Rev. 2011; 1: CD001561
- Low-fat dietary pattern and risk of cardiovascular disease: the Women's Health Initiative Randomized Controlled Dietary Modification Trial.JAMA. 2006; 295: 655-666
- Cardiovascular effects of intensive lifestyle intervention in type 2 diabetes.N Engl J Med. 2013; 369: 145-154
- Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin.N Engl J Med. 2002; 346: 393-403
- Effects on blood pressure of reduced dietary sodium and the Dietary Approaches to Stop Hypertension (DASH) diet. DASH-Sodium Collaborative Research Group.N Engl J Med. 2001; 344: 3-10
- Adherence to heart-healthy behaviors in a sample of the US population.Prev Chronic Dis. 2005; 2: A18
- Primary prevention of cardiovascular disease with a Mediterranean diet.N Engl J Med. 2013; 368: 1279-1290
- A strategy to reduce cardiovascular disease by more than 80%.BMJ. 2003; 326: 1419-1424
- The Polypill in the prevention of cardiovascular diseases: key concepts, current status, challenges, and future directions.Circulation. 2010; 122: 2078-2088
- Combination pharmacotherapy to prevent cardiovascular disease: present status and challenges.Eur Heart J. 2014; 35: 353-364
- Blood cholesterol and vascular mortality by age, sex, and blood pressure: a meta-analysis of individual data from 61 prospective studies with 55,000 vascular deaths.Lancet. 2007; 370: 1829-1839
- Age-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for one million adults in 61 prospective studies.Lancet. 2002; 360: 1903-1913
- Risk factor thresholds: their existence under scrutiny.BMJ. 2002; 324: 1570-1577
- Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials.Lancet. 2010; 376: 1670-1681
- Effects of different blood-pressure-lowering regimens on major cardiovascular events: results of prospectively-designed overviews of randomised trials.Lancet. 2003; 362: 1527-1535
- Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein.N Engl J Med. 2008; 359: 2195-2207
- Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia.N Engl J Med. 1995; 333: 1301-1307
- Primary prevention of acute coronary events with lovastatin in men and women with average cholesterol levels.JAMA. 1998; 279: 1615-1622
- Primary prevention of cardiovascular disease with pravastatin in Japan (MEGA Study): a prospective randomised controlled trial.Lancet. 2006; 368: 1155-1163
- Prevention of coronary and stroke events with atorvastatin in hypertensive patients who have average or lower-than-average cholesterol concentrations, in the Anglo-Scandinavian Cardiac Outcomes Trial-Lipid Lowering Arm (ASCOT-LLA): a multicentre randomised controlled trial.Lancet. 2003; 361: 1149-1158
- Primary prevention of cardiovascular disease with atorvastatin in type 2 diabetes in the Collaborative Atorvastatin Diabetes Study (CARDS): multicentre randomized placebo-controlled trial.Lancet. 2004; 364: 685-696
- Efficacy and safety of atorvastatin in the prevention of cardiovascular end points in subjects with type 2 diabetes.Diabetes Care. 2006; 29: 1478-1485
- Pravastatin in elderly individuals at risk of vascular disease (PROSPER): a randomised controlled trial.Lancet. 2002; 360: 1623-1630
- MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20 536 high-risk individuals: a randomised placebo-controlled trial.Lancet. 2002; 360: 7-22
- The effects of lowering LDL cholesterol with statin therapy in people at low risk of vascular disease: meta-analysis of individual data from 27 randomised trials.Lancet. 2012; 380: 581-590
- Updated national and international hypertension guidelines: a review of current recommendations.Drugs. 2014; 74: 2033-2051
- Why randomized controlled trials fail but needn’t: 1. Failure to gain “coal-face” commitment and to use the uncertainty principle.CMAJ. 2000; 162: 1311-1314
- Canadian Cardiovascular Society guidelines for the diagnosis and management of stable ischemic heart disease.Can J Cardiol. 2014; 30: 837-849
- Review of blood pressure control rates and outcomes.J Am Soc Hypertens. 2014; 8: 127-141
Article info
Publication history
Published online: July 08, 2015
Accepted:
July 1,
2015
Received:
June 24,
2015
Footnotes
See editorial by Waters and Chau, pages 275-277 of this issue.
See page 316 for disclosure information.
Identification
Copyright
© 2016 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.
