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

Bosch J 1 , Lonn EM 1 , Dagenais GR 2 , Gao P 1 , Lopez-Jaramillo P 3 , Zhu J 4 Show all authors , Pais P 5 , Avezum A 6 , Sliwa K 7 , Chazova IE 8 , Peters RJG 9 , Held C 10 , Yusoff K 11 , Lewis BS 12 , Toff WD 13 , Khunti K 14 , Reid CM 15 , Leiter LA 16 , Yusuf S 1 , Hart RG 1

Affiliations 

  • 1 Population Health Research Institute, Hamilton Health Sciences, ON, Canada (J.B., E.M.L., P.G., R.G.H., S.Y.)
  • 2 Institut Universitaire de Cardiologie et Pneumologie de Québec, Université Laval, QC, Canada (G.R.D.)
  • 3 Instituto Masira, Facultad de Salud, Universidad de Santander, Bucaramanga, Colombia (P.L.-J.)
  • 4 Fu Wai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing (J.Z.)
  • 5 St. John's Research Institute, Bangalore, India (P.P.)
  • 6 Dante Pazzanese Institute of Cardiology and Sao Paulo University, São Paulo, Brazil (A.A.)
  • 7 Hatter Institute for Cardiovascular Research in Africa, Department of Medicine, University of Cape Town, Soweto Cardiovascular Research Group, South Africa (K.S.)
  • 8 National Medical Research Centre of Cardiology, Moscow, Russia (I.E.C.)
  • 9 Department of Cardiology, Academic Medical Center, Amsterdam, the Netherlands (R.J.G.P.)
  • 10 Uppsala Clinical Research Centre and Institute for Medical Sciences, Cardiology, Uppsala University, Uppsala Academic Hospital, Sweden (C.H.)
  • 11 Universiti Teknologi Majlis Amansh Rakyat, Selayang, Malaysia (K.Y.)
  • 12 Lady Davis Carmel Medical Center, Ruth and Bruce Rappaport School of Medicine, Technion-Israel Institute of Technology, Haifa, Israel (B.S.L.)
  • 13 University of Leicester and University Hospitals of Leicester NHS Trust, Leicester, United Kingdom (W.D.T.)
  • 14 Leicester Diabetes Centre, University of Leicester, United Kingdom (K. K.)
  • 15 School of Public Health and Preventive Medicine, Curtin University, Perth, Western Australia (C.M.R.)
  • 16 Li Ka Shing Knowledge Institute and Keenan Research Centre for Biomedical Science, St. Michael's Hospital, University of Toronto, ON, Canada (L.A.L.)
Stroke, 2021 08;52(8):2494-2501.
PMID: 33985364 DOI: 10.1161/STROKEAHA.120.030790

Abstract

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.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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