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.

College of Medicine University of the Philippines Pedro Gil Street Taft Ave Ermita Manila 1000 Metro Manila Philippines

Dante Pazzanese Institute of Cardiology and Sao Paulo University Av Dr Dante Pazzanese 500 Vila Mariana São Paulo SP 04012 909 Brazil

Department of Cardiovascular Sciences University of Leicester University Rd Leicester LE1 7RH UK

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

Fu Wai Hospital Chinese Academy of Medical Sciences and Peking Union Medical College 9 Dongdan 3rd Alley Dong Dan Dongcheng Beijing

HCor Hospital do Coração Des Eliseu Guilherme 147 Paraíso São Paulo SP 04004 030 Brazil

Hungarian Institute of Cardiology Semmelweis University Budapest Hungary

Institut Universitaire de Cardiologie et Pneumologie de Québec Université Laval 2725 Ch Ste Foy Québec QC G1V 4G5 Canada

Institute of Cardiology Narodnoho Opolchennya St 5 Kiev 03680 Ukraine

Instituto Cardiovascular de Rosario DSR Bv Oroño 440 S2000 Rosario Santa Fe Argentina

Instituto Masira Facultad de Salud Universidad de Santander Calle 70 No 55 210 Bucaramanga Colombia

Lady Davis Carmel Medical Center Ruth and Bruce Rappaport School of Medicine Technion Israel Institute of Technology Efron St 1 Haifa Israel

Leicester Diabetes Centre Gwendolen Rd Leicester LE5 4PW UK

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

School of Public Health and Preventive Medicine Monash University 553 St Kilda Rd Melbourne VIC 3004 Australia

St John's Medical College Sarjarpur Road Bangalore Karnataka 560034 India

St John's Research Institute 100 Feet Rd John Nagar Koramangala Bangalore Karnataka 560034 India

The Department of Cardiology Academic Medical Center Meibergdreef 9 1105 AZ Amsterdam Netherlands

The Department of Medicine 1200 Main St West McMaster University Hamilton ON L8N 3Z5 Canada

The Population Health Research Institute Hamilton Health Sciences 237 Barton Street East Hamilton Ontario L8L 2X2 Canada

The School of Public Health Curtin University Kent St Bentley Perth WA 6102 Australia

The School of Rehabilitation Science McMaster University IAHS Room 403 1400 Main St West Hamilton ON L8S 1C7 Canada

The Uppsala Clinical Research Centre and Institute for Medical Sciences Cardiology Uppsala University Uppsala Academic Hospital Dag Hammarskjölds Väg 21 752 37 Uppsala Sweden

UK and National Institute for Health Research Leicester Biomedical Research Centre Glenfield Hospital Groby Road Leicester LE3 9QP UK

Universiti Teknologi Majlis Amansh Rakyat Jalan Ilmu 1 1 40450 Shah Alam Selangor Malaysia

University College Sedaya International University UCSI Heights 1 Jalan Puncak Menara Gading Taman Connaught 56000 Cheras Wilayah Persekutuan Kuala Lumpur Malaysia

University Hospital Motol 5 Úvalu 84 150 06 Praha 5 Czechia

Eur Heart J. 2021 Aug 17;42(31):3008-3010. doi: 10.1093/eurheartj/ehab208. PubMed

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ClinicalTrials.gov
NCT00468923