CRediT contribution statement
Borislava Mihaylova (https://orcid.org/0000-0002-0951-1304) (Professor of Health Economics): Conceptualization, Methodology, Software, Validation, Investigation, Writing - Original Draft, Writing - Review & Editing, Visualization, Supervision, Project administration, Funding acquisition.
Runguo Wu (https://orcid.org/0000-0002-6523-5754) (Senior Health Economist): Methodology, Software, Validation, Formal analysis, Data Curation, Writing - Original Draft, Writing - Review & Editing, Visualization.
Junwen Zhou (https://orcid.org/0000-0002-6812-0944) (Senior Researcher in Health Economics): Methodology, Software, Validation, Formal analysis, Data Curation, Writing - Original Draft, Writing - Review & Editing, Visualization.
Claire Williams (https://orcid.org/0000-0002-3005-1541) (Senior Researcher in Health Economics): Methodology, Validation, Formal analysis, Data Curation, Writing - Original Draft, Writing - Review & Editing, Visualization.
Iryna Schlackow (https://orcid.org/0000-0002-4154-1431) (Senior Researcher in Health Economics): Methodology, Software, Formal analysis, Data Curation, Writing - Review & Editing, Funding acquisition.
Jonathan Emberson (https://orcid.org/0000-0001-7792-9422) (Professor of Medical Statistics and Epidemiology): Methodology, Investigation, Resources, Writing - Review & Editing, Funding acquisition.
Christina Reith (https://orcid.org/0000-0001-7448-9847) (Senior Clinical Research Fellow): Investigation, Resources, Writing - Review & Editing, Funding acquisition.
Anthony Keech (https://orcid.org/0000-0002-9426-9136) (Professor of Medicine, Cardiology and Epidemiology): Methodology, Investigation, Resources, Writing - Review & Editing.
John Robson (https://orcid.org/0000-0001-6889-0415) (Clinical Reader in Primary Care): Methodology, Investigation, Writing - Review & Editing, Supervision.
Richard Parnell (Public Representative): Investigation, Writing - Review & Editing, Visualization.
Jane Armitage (https://orcid.org/0000-0001-8691-9226) (Professor of Clinical Trials and Epidemiology): Methodology, Investigation, Resources, Writing - Review & Editing, Funding acquisition.
Alastair Gray (https://orcid.org/0000-0003-0239-7278) (Professor of Health Economics): Methodology, Investigation, Writing - Review & Editing, Funding acquisition.
John Simes (Professor of Clinical Epidemiology): Methodology, Investigation, Resources, Writing - Review & Editing.
Colin Baigent (https://orcid.org/0000-0003-4856-7420) (Professor of Epidemiology): Conceptualization, Methodology, Investigation, Resources, Writing - Review & Editing, Supervision, Funding acquisition.
Acknowledgements
Members of the project oversight group: Colin Baigent, Alison Gater, Borislava Mihaylova, Stephen Morris, Paul Roderick (chairperson), Natalie Rowland, Peter Sever and Liam Smeeth.
We thank the external members of our project oversight group for their guidance and support throughout the project development. Particular thanks are due to Alison Gater, a representative of the general public on the committee, for her helpful insights throughout the project and her contribution to project dissemination. We also thank Kenneth Wilkinson, a member of the project management group representing the general public from April 2019 to May 2022, and further members of the public with whom we discussed the project and emerging results, including members of the OxPop Public Advisory Panel, participating in the meeting held on 26 November 2022 in Oxford, UK.
This research has been conducted using data from Cholesterol Treatment Trialists’ Collaboration www.cttcollaboration.org/, UK Biobank Resource under Application Number 56757 www.ukbiobank.ac.uk, and Whitehall II study www.ucl.ac.uk/epidemiology-health-care/research/epidemiology-and-public-health/research/whitehall-ii. We thank all the participants, staff and other contributors to these resources. Cholesterol Treatment Trialists’ Collaborators.
CTT secretariat: J Armitage, C Baigent, E Barnes, L Blackwell, R Collins, K Davies, J Emberson, J Fulcher, H Halls, WG Herrington, L Holland, A Keech, A Kirby, B Mihaylova, R O’Connell, D Preiss, C Reith, J Simes and K Wilson.
CTT Collaborating trialists: A to Z trial (phase Z) M Blazing, E Braunwald, J de Lemos, S Murphy; T Pedersen, M Pfeffer, H White and S Wiviott; AFCAPS/TEXCAPS (AirForce/Texas Coronary Atherosclerosis Prevention Study) M Clearfield, JR Downs, A Gotto and S Weis; ALERT (Assessment of Lescol in Renal Transplantation) B Fellström, H Holdaas (deceased), A Jardine and TR Pedersen; ALLHAT (Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial) D Gordon, B Davis; C Furberg, R Grimm, S Pressel, J Probstfield, M Rahman and L Simpson; ALLIANCE (Aggressive Lipid-Lowering Initiation Abates New Cardiac Events) M Koren; ASCOT (Anglo-Scandinavian Cardiac Outcomes Trial) B Dahlöf, A Gupta, N Poulter, P Sever and H Wedel; ASPEN (Atorvastatin Study for the Prevention of Coronary Heart Disease Endpoints in Non-Insulin Dependent Diabetes Mellitus) RH Knopp (deceased); AURORA (A study to evaluate the Use of Rosuvastatin in subjects On Regular haemodialysis: an Assessment of survival and cardiovascular events) S Cobbe, B Fellström, H Holdaas (deceased), A Jardine, R Schmieder and F Zannad; CARDS (Collaborative Atorvastatin Diabetes Study) DJ Betteridge (deceased), HM Colhoun, PN Durrington, J Fuller (deceased), GA Hitman and A Neil; CARE (Cholesterol And Recurrent Events Study) E Braunwald, B Davis, CM Hawkins, L Moyé, M Pfeffer and F Sacks; CORONA (Controlled Rosuvastatin Multinational Trial in Heart Failure) J Kjekshus, H Wedel and J Wikstrand; 4D (Die Deutsche Diabetes Dialyse Studie) C Wanner and V Krane; GISSI (Gruppo Italiano per lo Studio della Sopravvivenza nell’Infarto miocardico) Heart Failure and Prevention trials: MG Franzosi, R Latini, D Lucci, A Maggioni;, R Marchioli, EB Nicolis, L Tavazzi and G Tognoni; HOPE-3 J Bosch, E Lonn and S Yusuf; HPS (Heart Protection Study) J Armitage, L Bowman, R Collins, A Keech, M Landray, S Parish, R Peto and P Sleight (deceased); IDEAL (Incremental Decrease in Endpoints through Aggressive Lipid-lowering) JJP Kastelein and TR Pedersen; JUPITER (Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin) R Glynn, A Gotto, JJP Kastelein, W Koenig, J Macfadyen and PM Ridker; LIPID (Long-term Intervention with Pravastatin in Ischaemic Disease) A Keech, S MacMahon, I Marschner, A Tonkin, J Shaw, J Simes and H White; LIPS (Lescol Intervention Prevention Study) PW Serruys; Post-CABG (Post-Coronary Artery Bypass Graft Study) G Knatterud (deceased); PROSPER (Prospective Study of Pravastatin in the Elderly at Risk) GJ Blauw, S Cobbe, I Ford, M Murphy, GJ Blauw, P Macfarlane, C Packard, N Sattar, J Shepherd (deceased) and S Trompet; PROVE-IT (Pravastatin or Atorvastatin Evaluation and Infection Therapy) E Braunwald, CC Cannon and S Murphy; SEARCH (Study of Effectiveness of Additional Reductions in Cholesterol and Homocysteine) R Collins, J Armitage, L Bowman, R Bulbulia, R Haynes, S Parish, R Peto and P Sleight (deceased); SPARCL (Stroke Prevention by Aggressive Reduction in Cholesterol Levels) P Amarenco and K Welch; 4S (Scandinavian Simvastatin Survival Study) J Kjekshus, T Pedersen and L Wilhelmsen; TNT (Treating to New Targets) P Barter, A Gotto, J La Rosa, JJP Kastelein and J Shepherd (deceased); WOSCOPS (West of Scotland Coronary Prevention Study) S Cobbe, I Ford, S Kean, P Macfarlane, C Packard, M Roberston, N Sattar, J Shepherd (deceased) and R Young. Other CTT Members: H Arashi, R Clarke, M Flather, S Goto, U Goldbourt, J Hopewell, K Hovingh, G Kitas, C Newman, M Sabatine, GG Schwartz, L Smeeth, J Tobert, J Varigos and J Yamamguchi.
Further support from the British Heart Foundation, the UK Medical Research Council, the National Institute for Health Research Barts Biomedical Research Centre (NIHR203330) and NHMRC – Australia is acknowledged.
Data-sharing statement
Requests for individual patient data from trials contributing into the Cholesterol Treatment Trialists’ Collaboration should be made directly to the data custodians of each trial (see Cholesterol Treatment Trialists’ data policy on www.cttcollaboration.org/). Other data underlining this work may be obtained from third parties (UK Biobank www.ukbiobank.ac.uk/; Whitehall II study www.ucl.ac.uk/epidemiology-health-care/research/epidemiology-and-public-health/research/whitehall-ii; Health Survey for England https://beta.ukdataservice.ac.uk/datacatalogue/series/series?id=2000021) and are not publicly available. Researchers can apply to use the UK Biobank resource, Whitehall II study data, and UK Data Service data. For all other queries, please contact the corresponding author.
Ethics statement
Ethics committee approval was not required for this secondary research study.
Information governance statement
University of Oxford and Queen Mary University of London are committed to handling all personal information in line with the UK Data Protection Act (2018) and the General Data Protection Regulation (EU GDPR) 2016/679. Under the Data Protection legislation, the University of Oxford is the Data Controller in relation to use of UK Biobank and Cholesterol Treatment Trialists’ Collaboration data in the study, and you can find out more about how we handle personal data, including how to exercise your individual rights, and the contact details for our Data Protection Officer here: https://compliance.admin.ox.ac.uk/data-protection-policy. Under the Data Protection legislation, Queen Mary University of London is the Data Controller in relation to use of UK Biobank and Whitehall II data in the study, and you can find out more about how we handle personal data, including how to exercise your individual rights, and the contact details for our Data Protection Officer here: https://www.qmul.ac.uk/privacy/media/arcs/policyzone/Data-Protection-Policy-v03.1.pdf.
Disclosure of interests
Full disclosure of interests: Completed ICMJE forms for all authors, including all related interests, are available in the toolkit on the NIHR Journals Library report publication page at https://doi.org/10.3310/KDAP7034.
Primary conflicts of interest: Borislava Mihaylova reports grants from the National Institute for Health and Care Research (NIHR) and Barts Charity (London, UK) during the conduct of the study and membership of the following committees: NIHR Programme Grants for Applied Research (PGfAR) Subpanel A (2016–20), Value in Health Advisory Board (2019–present), the European Society of Cardiology (ESC) Clinical Practice Guidelines committee (2022–present) and the Task Force for the 2019 ESC/EAS Guidelines for the management of dyslipidaemias. Christina Reith reports grants from the NIHR, British Heart Foundation, Medical Research Council (MRC) and National Health and Medical Research Council (NHMRC)-Australia during the conduct of the study and membership of the Clinical Data Interchange Standards Consortium (CDISC) Board. Anthony Keech reports grants from the NHMRC-Australia, Amgen (Thousand Oaks, CA, USA), Mylan (Canonsburg, PA, USA) and Abbott Laboratories (Chicago, IL, USA) during the conduct of the study; consulting fees from AstraZeneca (Cambridge, UK); and speaker fees from Sanofi (Paris, France) and Pfizer (Sandwich, UK). John Robson reports grants from Barts Charity and NIHR during the conduct of the study. Richard Parnell reports membership of the following committees: EME Prioritisation Group 1 June 2015–1 June 2016, EME Strategy Advisory Committee 1 November 2019–31 December 2020, and EME – Funding Committee Members 1 June 2016–1 June 2020. Jane Armitage reports grants from the NIHR, British Heart Foundation, MRC and NHMRC-Australia and Novartis (Basel, Switzerland) during the conduct of the study and membership of the of BHF Clinical Studies Committee. Alastair Gray reports grants from the NIHR, British Heart Foundation and MRC during the conduct of the study. John Simes reports grants from Bayer (Leverkusen, Germany), Roche (Basel, Switzerland), Bristol Myers Squibb (Uxbridge, UK), AstraZeneca, MSD (London, UK), Pfizer, NHMRC-Australia and consulting fee paid to his institution from Detsamma Investments Pty Ltd as FivepHusion (NSW, Australia) during the conduct of the study. Colin Baigent reports grants from the NIHR, MRC, Boehringer Ingelheim (Ingelheim am Rhein, Germany) and Health Data Research UK (London, UK) during the conduct of the study and membership of the European Society of Cardiology’s Committee on Practice Guidelines (2018–present).
Publications
Peer-reviewed publications
Zhou J, Wu R, Williams C, Emberson J, Reith C, Keech A, et al. Prediction models for individual-level healthcare costs associated with cardiovascular events in the UK. PharmacoEconomics 2023;41:547–59. https://doi.org/10.1007/s40273-022-01219-6
Wu R, Williams C, Zhou J, Schlackow I, Emberson J, Reith C, et al. Long-term cardiovascular risks and statin treatment impact on socioeconomic inequalities: a microsimulation model. Br J Gen Pract 2024;74:e189–98. https://doi.org/10.3399/BJGP.2023.0198
Zhou J, Williams C, Keng MJ, Wu R, Mihaylova B. Estimating costs associated with disease model states using generalized linear models: a tutorial. PharmacoEconomics 2023;74:e189–e198. https://doi.org/10.1007/s40273-023-01319-x
Mihaylova B, Wu R, Zhou J, Williams C, Emberson J, Schlackow I, et al. Lifetime effects and cost-effectiveness of standard and higher-intensity statin therapy across population categories in the UK: a microsimulation modelling study. Lancet Regional Health-Europe 2024;40:100887. https://doi.org/10.1016/j.lanepe.2024.100887
Mihaylova B, Wu R, Zhou J, Williams C, Schlackow I, Emberson J, et al. Lifetime effects and cost-effectiveness of statin therapy for older people in the United Kingdom: a modelling study. Heart 2024;110:1277–85. https://doi.org/10.1136/heartjnl-2024-324052
Published conference abstracts
Wu R, Williams C, Schlackow I, Zhou J, Emberson J, Reith C, et al. A model of lifetime health outcomes in cardiovascular disease based on clinical trials and large cohorts. Eur Heart J 2021;42:ehab724.3149. https://doi.org/10.1093/eurheartj/ehab724.3149
Mihaylova B, Wu R, Williams C, Zhou J, Schlackow I, Emberson J, et al. Cost-effectiveness of statin therapy in categories of patients in the UK. Eur Heart J 2022;43(Suppl. 2). https://doi.org/10.1093/eurheartj/ehac544.2841
Wu R, Williams C, Schlackow I, Zhou J, Emberson J, Reith C, et al. P70 calibrating cardiovascular disease policy model using large cohort data. Value Health 2022;25:S16. https://doi.org/10.1016/j.jval.2021.11.068. (www.sciencedirect.com/science/article/pii/S1098301521018635).
Wu R, Williams C, Zhou J, Schlackow I, Emberson J, Reith C, et al. Benefit accrual with cardiovascular disease prevention and effects of discontinuation: a modelling study. Eur Heart J 2022;43(Suppl. 2). https://doi.org/10.1093/eurheartj/ehac544.2850
Zhou J, Wu R, Williams C, Emberson J, Reith C, Keech A, et al. Impact of cardiovascular events on primary and hospital care costs: findings from UK Biobank study. Eur Heart J 2022;43(Suppl. 2). https://doi.org/10.1093/eurheartj/ehac544.2852
Zhou J, Wu R, Williams C, Mihaylova B. P55 excess annual hospital costs due to cardiovascular events in a contemporary UK population to inform health technology assessments. Value Health 2022;25:S12. https://doi.org/10.1016/j.jval.2021.11.053. (www.sciencedirect.com/science/article/pii/S1098301521018489).
Disclaimers
This article presents independent research funded by the National Institute for Health and Care Research (NIHR). The views and opinions expressed by authors in this publication are those of the authors and do not necessarily reflect those of the NHS, the NIHR, the HTA programme or the Department of Health and Social Care. If there are verbatim quotations included in this publication the views and opinions expressed by the interviewees are those of the interviewees and do not necessarily reflect those of the authors, those of the NHS, the NIHR, the HTA programme or the Department of Health and Social Care.