{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,11]],"date-time":"2025-09-11T19:11:56Z","timestamp":1757617916477,"version":"3.44.0"},"reference-count":33,"publisher":"Springer Science and Business Media LLC","issue":"5","license":[{"start":{"date-parts":[[2025,5,24]],"date-time":"2025-05-24T00:00:00Z","timestamp":1748044800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,5,24]],"date-time":"2025-05-24T00:00:00Z","timestamp":1748044800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Appl Health Econ Health Policy"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Background<\/jats:title>\n            <jats:p>Despite the decreased risk of cardiovascular disease (CVD) with statins, there remains an unfulfilled clinical need to prevent CVD events and premature mortality through further cholesterol-modifying interventions. In people with established CVD taking a statin, lipid therapy escalation to reduce low-density lipoprotein cholesterol (LDL-C) or non-high-density lipoprotein cholesterol (non-HDL-C) levels may lower the risk of CVD hospital admissions and improve survival. However, the cost-effectiveness of different cholesterol treatment escalation thresholds is uncertain.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Objective<\/jats:title>\n            <jats:p>This study aimed to identify the most cost-effective cholesterol threshold for escalating lipid therapy in people with established CVD who are taking a statin, to support the 2023 update of the NICE guideline on CVD in England.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>A cohort Markov model with a yearly cycle length was developed to compare the lifetime costs and quality-adjusted life years (QALYs) of various LDL-C treatment escalation thresholds (0\u20134.0 mmol\/L), using a combination of treatment effects from an original network meta-analysis of randomised controlled trials (RCTs), real-world data for estimating baseline cholesterol levels and CVD event rates from a published meta-analysis of statin RCTs. The model used the following CVD events: ischaemic stroke; transient ischaemic attack; peripheral artery disease; myocardial infarction; unstable angina; coronary revascularisation; and mortality. The model also used evidence-based estimates of resource use and costs, and published quality of life data. Baseline LDL-C levels and CVD hospital admission rates were estimated through a bespoke analysis of the English primary care data from Clinical Practice Research Datalink (CPRD), linked to Hospital Episode Statistics Admitted Patient Care (HES) and Office for National Statistics (ONS) death registrations.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>Data from 590,917 adult individuals (61.7% men) with CVD on a statin in primary care between 1 January 2013 and 28 February 2020 were included in the CPRD-HES-ONS analysis. The most cost-effective threshold for lipid therapy escalation was an LDL-C of 2.2 mmol\/L (or equivalent non-HDL-C of 2.9 mmol\/L) at NICE\u2019s lower cost per QALY of \u00a320,000. An LDL-C of 2.0 mmol\/L (or equivalent non-HDL-C of 2.6 mmol\/L) was the most cost-effective treatment escalation threshold in a significant proportion (38%) of probabilistic simulations and produced more health. At this threshold, the model predicted that 42% of people with CVD would require combination therapy with ezetimibe while 19% would require an injectable drug such as inclisiran. At NICE\u2019s upper cost per QALY of \u00a330,000, the most cost-effective LDL-C treatment escalation threshold was 1.7 mmol\/L (or equivalent non-HDL-C of 2.2 mmol\/L).<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>The results demonstrate the importance of establishing evidence of cost-effectiveness for cholesterol treatment escalation thresholds. The study\u2019s findings support the updated NICE guideline recommending a threshold of 2.0 mmol\/L LDL-C (or equivalent non-HDL-C of 2.6 mmol\/L) for secondary prevention of CVD.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1007\/s40258-025-00977-6","type":"journal-article","created":{"date-parts":[[2025,5,24]],"date-time":"2025-05-24T07:07:11Z","timestamp":1748070431000},"page":"869-883","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Using a Markov Model and Real-World Evidence to Identify the Most Cost-Effective Cholesterol Treatment Escalation Threshold for the Secondary Prevention of Cardiovascular Disease"],"prefix":"10.1007","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-6405-304X","authenticated-orcid":false,"given":"Alfredo","family":"Mariani","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Syed","family":"Mohiuddin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patrick","family":"Muller","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eleanor","family":"Samarasekera","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sharon A.","family":"Swain","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joseph","family":"Mills","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Riyaz","family":"Patel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Preiss","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eduard","family":"Shantsila","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Beatrice C.","family":"Downing","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Lonergan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shaun","family":"Rowark","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicky J.","family":"Welton","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rachael","family":"Williams","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Wonderling","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,5,24]]},"reference":[{"issue":"13","key":"977_CR1","doi-asserted-by":"publisher","first-page":"1635","DOI":"10.1093\/eurheartj\/ehs092","volume":"33","author":"J Perk","year":"2012","unstructured":"Perk J, De Backer G, Gohlke H, Graham I, Reiner Z, Verschuren M, et al. 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S.M. conducted quality assurance of the model. J.M., R.P., D.P. and E.Sh. are clinicians who agreed the clinical validity of the model structure and its parameters and assumptions. S.S. led the guideline development team, E.Sa. led the systematic review of trial evidence. P.M., S.R., M.L. and R.W. led the analysis of CPRD data. B.C.D. and N.J.W. conducted the network meta-analysis and D.W. led the economic model development team. A.M., S.M. and D.W. drafted the manuscript, and all authors commented on the draft and read and approved the final manuscript. The authors alone are responsible for the content and writing of the manuscript.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Author Contributions"}},{"value":"No external funding was received for conducting this study. B.C.D. and N.J.W. were supported by the Guidelines Technical Support Unit at the University of Bristol which is funded by NICE. NICE funded access to CPRD data and research services for the purposes of this study was granted under a Memorandum of Understanding with the MHRA.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Funding"}},{"value":"The authors have no conflicts of interest to declare. NDPH, University of Oxford, is coordinating the ORION-4 trial of inclisiran, with funding from Novartis, but D.P. receives no personal support from the grant and NDPH has a staff policy of not accepting honoraria from industry.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflicts of Interest"}},{"value":"A version of the model with confidential data replaced with dummy data may be available by reasonable request from the corresponding author.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Data and Code Availability"}},{"value":"Not applicable.","order":6,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to Participate"}},{"value":"Not applicable.","order":7,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for Publication"}},{"value":"The Research Data Governance process reviewed and approved the protocol for the CPRD aspects of this study (22_002517) on 30 January 2023.","order":8,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics Approval"}}]}}