Antihypertensives and Statin Therapy for Primary Stroke Prevention: A Secondary Analysis of the HOPE-3 Trial.

Aged Antihypertensive Agents / administration & dosage Double-Blind Method Drug Therapy, Combination Female Follow-Up Studies Humans Hydroxymethylglutaryl-CoA Reductase Inhibitors / administration & dosage Male Middle Aged Primary Prevention / methods Stroke / diagnostic imaging
blood pressure candesartan cardiovascular disease lipoprotein primary prevention statin

Journal

Stroke
ISSN: 1524-4628
Titre abrégé: Stroke
Pays: United States
ID NLM: 0235266

Informations de publication

Date de publication:
08 2021
Historique:
pubmed: 15 5 2021
medline: 5 1 2022
entrez: 14 5 2021
Statut: ppublish

Résumé

The HOPE-3 trial (Heart Outcomes Prevention Evaluation–3) found that antihypertensive therapy combined with a statin reduced first stroke among people at intermediate cardiovascular risk. We report secondary analyses of stroke outcomes by stroke subtype, predictors, treatment effects in key subgroups. Using a 2-by-2 factorial design, 12 705 participants from 21 countries with vascular risk factors but without overt cardiovascular disease were randomized to candesartan 16 mg plus hydrochlorothiazide 12.5 mg daily or placebo and to rosuvastatin 10 mg daily or placebo. The effect of the interventions on stroke subtypes was assessed. Participants were 66 years old and 46% were women. Baseline blood pressure (138/82 mm Hg) was reduced by 6.0/3.0 mm Hg and LDL-C (low-density lipoprotein cholesterol; 3.3 mmol/L) was reduced by 0.90 mmol/L on active treatment. During 5.6 years of follow-up, 169 strokes occurred (117 ischemic, 29 hemorrhagic, 23 undetermined). Blood pressure lowering did not significantly reduce stroke (hazard ratio [HR], 0.80 [95% CI, 0.59–1.08]), ischemic stroke (HR, 0.80 [95% CI, 0.55–1.15]), hemorrhagic stroke (HR, 0.71 [95% CI, 0.34–1.48]), or strokes of undetermined origin (HR, 0.92 [95% CI, 0.41–2.08]). Rosuvastatin significantly reduced strokes (HR, 0.70 [95% CI, 0.52–0.95]), with reductions mainly in ischemic stroke (HR, 0.53 [95% CI, 0.37–0.78]) but did not significantly affect hemorrhagic (HR, 1.22 [95% CI, 0.59–2.54]) or strokes of undetermined origin (HR, 1.29 [95% CI, 0.57–2.95]). The combination of both interventions compared with double placebo substantially and significantly reduced strokes (HR, 0.56 [95% CI, 0.36–0.87]) and ischemic strokes (HR, 0.41 [95% CI, 0.23–0.72]). Among people at intermediate cardiovascular risk but without overt cardiovascular disease, rosuvastatin 10 mg daily significantly reduced first stroke. Blood pressure lowering combined with rosuvastatin reduced ischemic stroke by 59%. Both therapies are safe and generally well tolerated. URL: https://www.clinicaltrials.gov; Unique identifier: NCT00468923.

Sections du résumé

Background and Purpose
The HOPE-3 trial (Heart Outcomes Prevention Evaluation–3) found that antihypertensive therapy combined with a statin reduced first stroke among people at intermediate cardiovascular risk. We report secondary analyses of stroke outcomes by stroke subtype, predictors, treatment effects in key subgroups.
Methods
Using a 2-by-2 factorial design, 12 705 participants from 21 countries with vascular risk factors but without overt cardiovascular disease were randomized to candesartan 16 mg plus hydrochlorothiazide 12.5 mg daily or placebo and to rosuvastatin 10 mg daily or placebo. The effect of the interventions on stroke subtypes was assessed.
Results
Participants were 66 years old and 46% were women. Baseline blood pressure (138/82 mm Hg) was reduced by 6.0/3.0 mm Hg and LDL-C (low-density lipoprotein cholesterol; 3.3 mmol/L) was reduced by 0.90 mmol/L on active treatment. During 5.6 years of follow-up, 169 strokes occurred (117 ischemic, 29 hemorrhagic, 23 undetermined). Blood pressure lowering did not significantly reduce stroke (hazard ratio [HR], 0.80 [95% CI, 0.59–1.08]), ischemic stroke (HR, 0.80 [95% CI, 0.55–1.15]), hemorrhagic stroke (HR, 0.71 [95% CI, 0.34–1.48]), or strokes of undetermined origin (HR, 0.92 [95% CI, 0.41–2.08]). Rosuvastatin significantly reduced strokes (HR, 0.70 [95% CI, 0.52–0.95]), with reductions mainly in ischemic stroke (HR, 0.53 [95% CI, 0.37–0.78]) but did not significantly affect hemorrhagic (HR, 1.22 [95% CI, 0.59–2.54]) or strokes of undetermined origin (HR, 1.29 [95% CI, 0.57–2.95]). The combination of both interventions compared with double placebo substantially and significantly reduced strokes (HR, 0.56 [95% CI, 0.36–0.87]) and ischemic strokes (HR, 0.41 [95% CI, 0.23–0.72]).
Conclusions
Among people at intermediate cardiovascular risk but without overt cardiovascular disease, rosuvastatin 10 mg daily significantly reduced first stroke. Blood pressure lowering combined with rosuvastatin reduced ischemic stroke by 59%. Both therapies are safe and generally well tolerated.
Registration
URL: https://www.clinicaltrials.gov; Unique identifier: NCT00468923.

Identifiants

DOI: 10.1161/STROKEAHA.120.030790 PMID: 33985364
pubmed: 33985364
doi: 10.1161/STROKEAHA.120.030790
doi:

Substances chimiques

Antihypertensive Agents 0
Hydroxymethylglutaryl-CoA Reductase Inhibitors 0

Banques de données

ClinicalTrials.gov
['NCT00468923']

Types de publication

Journal Article Multicenter Study Randomized Controlled Trial Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

2494-2501

Commentaires et corrections

Type : ErratumIn

Auteurs

Jackie Bosch (J)

Population Health Research Institute, Hamilton Health Sciences, ON, Canada (J.B., E.M.L., P.G., R.G.H., S.Y.).
School of Rehabilitation Science (J.B.), McMaster University, Hamilton, ON, Canada.

Eva M Lonn (EM)

Population Health Research Institute, Hamilton Health Sciences, ON, Canada (J.B., E.M.L., P.G., R.G.H., S.Y.).
Department of Medicine (E.M.L., R.G.H., S.Y.), McMaster University, Hamilton, ON, Canada.

Gilles R Dagenais (GR)

Institut Universitaire de Cardiologie et Pneumologie de Québec, Université Laval, QC, Canada (G.R.D.).

Peggy Gao (P)

Population Health Research Institute, Hamilton Health Sciences, ON, Canada (J.B., E.M.L., P.G., R.G.H., S.Y.).

Patricio Lopez-Jaramillo (P)

Instituto Masira, Facultad de Salud, Universidad de Santander, Bucaramanga, Colombia (P.L.-J.).

Jun Zhu (J)

Fu Wai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing (J.Z.).

Prem Pais (P)

St. John's Research Institute, Bangalore, India (P.P.).

Alvaro Avezum (A)

Dante Pazzanese Institute of Cardiology and Sao Paulo University, São Paulo, Brazil (A.A.).

Karen Sliwa (K)

Hatter Institute for Cardiovascular Research in Africa, Department of Medicine, University of Cape Town, Soweto Cardiovascular Research Group, South Africa (K.S.).

Irina E Chazova (IE)

National Medical Research Centre of Cardiology, Moscow, Russia (I.E.C.).

Ron J G Peters (RJG)

Department of Cardiology, Academic Medical Center, Amsterdam, the Netherlands (R.J.G.P.).

Claes Held (C)

Uppsala Clinical Research Centre and Institute for Medical Sciences, Cardiology, Uppsala University, Uppsala Academic Hospital, Sweden (C.H.).

Khalid Yusoff (K)

Universiti Teknologi Majlis Amansh Rakyat, Selayang, Malaysia (K.Y.).
University College Sedaya International University, Kuala Lumpur, Malaysia (K.Y.).

Basil S Lewis (BS)

Lady Davis Carmel Medical Center, Ruth and Bruce Rappaport School of Medicine, Technion-Israel Institute of Technology, Haifa, Israel (B.S.L.).

William D Toff (WD)

University of Leicester and University Hospitals of Leicester NHS Trust, Leicester, United Kingdom (W.D.T.).

Kamlesh Khunti (K)

Leicester Diabetes Centre, University of Leicester, United Kingdom (K. K.).

Christopher M Reid (CM)

School of Public Health and Preventive Medicine, Curtin University, Perth, Western Australia (C.M.R.).
Monash University, Melbourne, Victoria, Australia (C.M.R.).

Lawrence A Leiter (LA)

Li Ka Shing Knowledge Institute and Keenan Research Centre for Biomedical Science, St. Michael's Hospital, University of Toronto, ON, Canada (L.A.L.).

Salim Yusuf (S)

Population Health Research Institute, Hamilton Health Sciences, ON, Canada (J.B., E.M.L., P.G., R.G.H., S.Y.).
Department of Medicine (E.M.L., R.G.H., S.Y.), McMaster University, Hamilton, ON, Canada.

Robert G Hart (RG)

Population Health Research Institute, Hamilton Health Sciences, ON, Canada (J.B., E.M.L., P.G., R.G.H., S.Y.).
Department of Medicine (E.M.L., R.G.H., S.Y.), McMaster University, Hamilton, ON, Canada.

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Classifications MeSH

questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Sujet âgé › Antihypertensives and Statin Therapy for...
questionsmedicales.fr › Actions chimiques et utilisations › Actions pharmacologiques › Utilisations thérapeutiques › Agents cardiovasculaires › Antihypertenseurs › Antihypertensives and Statin Therapy for...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Méthodologie en recherche épidémiologique › Méthode en double aveugle › Antihypertensives and Statin Therapy for...
questionsmedicales.fr › Thérapeutique › Traitement médicamenteux › Association de médicaments › Antihypertensives and Statin Therapy for...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Caractéristiques des études épidémiologiques › Études épidémiologiques › Études de cohortes › Études de suivi › Antihypertensives and Statin Therapy for...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Antihypertensives and Statin Therapy for...
questionsmedicales.fr › Actions chimiques et utilisations › Actions pharmacologiques › Utilisations thérapeutiques › Agents régulateurs du métabolisme des lipides › Hypolipémiants › Anticholestérolémiants › Inhibiteurs de l'hydroxyméthylglutaryl-CoA réductase › Antihypertensives and Statin Therapy for...
questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Adulte d'âge moyen › Antihypertensives and Statin Therapy for...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Pratiques en santé publique › Prévention primaire › Antihypertensives and Statin Therapy for...
questionsmedicales.fr › Maladies cardiovasculaires › Maladies vasculaires › Angiopathies intracrâniennes › Accident vasculaire cérébral › Antihypertensives and Statin Therapy for...