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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

Bosch J 1 , Lonn EM 1 , Jung H 1 , Zhu J 2 , Liu L 2 , Lopez-Jaramillo P 3 Show all authors , Pais P 4 , Xavier D 4 , Diaz R 5 , Dagenais G 6 , Dans A 7 , Avezum A 8 , Piegas LS 9 , Parkhomenko A 10 , Keltai K 11 , Keltai M 11 , Sliwa K 12 , Held C 13 , Peters RJG 14 , Lewis BS 15 , Jansky P 16 , Yusoff K 17 , Khunti K 18 , Toff WD 19 , Reid CM 20 , Varigos J 20 , Joseph P 1 , Leiter LA 21 , Yusuf S 1

Affiliations 

  • 1 The Population Health Research Institute, Hamilton Health Sciences, 237 Barton Street East, Hamilton, Ontario L8L 2X2, Canada
  • 2 Fu Wai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 9 Dongdan 3rd Alley, Dong Dan, Dongcheng, Beijing
  • 3 Instituto Masira, Facultad de Salud, Universidad de Santander, Calle 70 No 55-210, Bucaramanga, Colombia
  • 4 St. John's Research Institute, 100 Feet Rd, John Nagar, Koramangala, Bangalore, Karnataka 560034, India
  • 5 Instituto Cardiovascular de Rosario, DSR, Bv. Oroño 440, S2000 Rosario, Santa Fe, Argentina
  • 6 Institut Universitaire de Cardiologie et Pneumologie de Québec, Université Laval, 2725 Ch Ste-Foy, Québec, QC G1V 4G5, Canada
  • 7 College of Medicine, University of the Philippines, Pedro Gil Street, Taft Ave, Ermita, Manila, 1000 Metro Manila, Philippines
  • 8 Dante Pazzanese Institute of Cardiology and Sao Paulo University, Av. Dr. Dante Pazzanese, 500 - Vila Mariana, São Paulo - SP, 04012-909, Brazil
  • 9 HCor-Hospital do Coração, Des. Eliseu Guilherme, 147 - Paraíso, São Paulo - SP, 04004-030, Brazil
  • 10 Institute of Cardiology, Narodnoho Opolchennya St, 5, Kiev 03680, Ukraine
  • 11 Hungarian Institute of Cardiology, Semmelweis University, Budapest, Hungary
  • 12 Department of Medicine, Hatter Institute for Cardiovascular Research, University of Cape Town, Soweto Cardiovascular Research Group, 4th, 5th and 6th Floor, Chris Barnard Building Faculty of Health Sciences, Private Bag X3 7935, Cape Town, South Africa
  • 13 The Uppsala Clinical Research Centre and Institute for Medical Sciences, Cardiology, Uppsala University, Uppsala Academic Hospital, Dag Hammarskjölds Väg 21, 752 37 Uppsala, Sweden
  • 14 The Department of Cardiology, Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, Netherlands
  • 15 Lady Davis Carmel Medical Center, Ruth and Bruce Rappaport School of Medicine, Technion-Israel Institute of Technology, Efron St 1, Haifa, Israel
  • 16 University Hospital Motol, V Úvalu 84, 150 06 Praha 5, Czechia
  • 17 Universiti Teknologi Majlis Amansh Rakyat, Jalan Ilmu 1/1, 40450 Shah Alam, Selangor, Malaysia
  • 18 Leicester Diabetes Centre, Gwendolen Rd, Leicester LE5 4PW, UK
  • 19 Department of Cardiovascular Sciences, University of Leicester, University Rd, Leicester LE1 7RH, UK
  • 20 School of Public Health and Preventive Medicine, Monash University, 553 St. Kilda Rd., Melbourne, VIC 3004, Australia
  • 21 Li Ka Shing Knowledge Institute and Keenan Research Centre for Biomedical Science, St. Michael's Hospital, University of Toronto, 209 Victoria St, Toronto, ON M5B 1T8, Canada
Eur Heart J, 2021 08 17;42(31):2995-3007.
PMID: 33963372 DOI: 10.1093/eurheartj/ehab225

Abstract

AIMS: Rosuvastatin (10 mg per day) compared with placebo reduced major adverse cardiovascular (CV) events by 24% in 12 705 participants at intermediate CV risk after 5.6 years. There was no benefit of blood pressure (BP) lowering treatment in the overall group, but a reduction in events in the third of participants with elevated systolic BP. After cessation of all the trial medications, we examined whether the benefits observed during the active treatment phase were sustained, enhanced, or attenuated.

METHODS AND RESULTS: After the randomized treatment period (5.6 years), participants were invited to participate in 3.1 further years of observation (total 8.7 years). The first co-primary outcome for the entire length of follow-up was the composite of myocardial infarction, stroke, or CV death [major adverse cardiovascular event (MACE)-1], and the second was MACE-1 plus resuscitated cardiac arrest, heart failure, or coronary revascularization (MACE-2). In total, 9326 (78%) of 11 994 surviving Heart Outcomes Prevention Evaluation (HOPE)-3 subjects consented to participate in extended follow-up. During 3.1 years of post-trial observation (total follow-up of 8.7 years), participants originally randomized to rosuvastatin compared with placebo had a 20% additional reduction in MACE-1 [95% confidence interval (CI), 0.64-0.99] and a 17% additional reduction in MACE-2 (95% CI 0.68-1.01). Therefore, over the 8.7 years of follow-up, there was a 21% reduction in MACE-1 (95% CI 0.69-0.90, P = 0.005) and 21% reduction in MACE-2 (95% CI 0.69-0.89, P = 0.002). There was no benefit of BP lowering in the overall study either during the active or post-trial observation period, however, a 24% reduction in MACE-1 was observed over 8.7 years.

CONCLUSION: The CV benefits of rosuvastatin, and BP lowering in those with elevated systolic BP, compared with placebo continue to accrue for at least 3 years after cessation of randomized treatment in individuals without cardiovascular disease indicating a legacy effect.

TRIAL REGISTRATION NUMBER: NCT00468923.

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

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