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      Cost-effectiveness of proprotein convertase subtilisin/kexin type 9 inhibition with evolocumab in patients with a history of myocardial infarction in Sweden

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          Abstract

          Aims

          To assess the cost-effectiveness of proprotein convertase subtilisin/kexin type 9 inhibition with evolocumab added to standard-of-care lipid-lowering treatment [maximum tolerated dose (MTD) of statin and ezetimibe] in Swedish patients with a history of myocardial infarction (MI).

          Methods and results

          Cost-effectiveness was evaluated using a Markov model based on Swedish observational data on cardiovascular event rates and efficacy from the FOURIER trial. Three risk profiles were considered: recent MI in the previous year; history of MI with a risk factor; and history of MI with a second event within 2 years. For each population, three minimum baseline low-density lipoprotein cholesterol (LDL-C) levels were considered: 2.5 mmol/L (≈100 mg/dL), based on the current reimbursement recommendation in Sweden; 1.8 mmol/L (≈70 mg/dL), based on 2016 ESC/EAS guidelines; and 1.4 mmol/L (≈55 mg/dL), or 1.0 mmol/L (≈40 mg/dL) for MI with a second event, based on 2019 ESC/EAS guidelines. Proprotein convertase subtilisin/kexin type 9 inhibition with evolocumab was associated with increased quality-adjusted life-years and costs vs. standard-of-care therapy. Incremental cost-effectiveness ratios (ICERs) were below SEK700 000 (∼€66 500), the generally accepted willingness-to-pay threshold in Sweden, for minimum LDL-C levels of 2.3 ( recent MI), 1.7 ( MI with a risk factor), and 1.7 mmol/L ( MI with a second event). Sensitivity analyses demonstrated that base-case results were robust to changes in model parameters.

          Conclusion

          Proprotein convertase subtilisin/kexin type 9 inhibition with evolocumab added to MTD of statin and ezetimibe may be considered cost-effective at its list price for minimum LDL-C levels of 1.7–2.3 mmol/L, depending on risk profile, with ICERs below the accepted willingness-to-pay threshold in Sweden.

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          Most cited references36

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          2019 ESC/EAS Guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk

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            Evolocumab and Clinical Outcomes in Patients with Cardiovascular Disease

            Evolocumab is a monoclonal antibody that inhibits proprotein convertase subtilisin-kexin type 9 (PCSK9) and lowers low-density lipoprotein (LDL) cholesterol levels by approximately 60%. Whether it prevents cardiovascular events is uncertain.
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              Low-density lipoproteins cause atherosclerotic cardiovascular disease. 1. Evidence from genetic, epidemiologic, and clinical studies. A consensus statement from the European Atherosclerosis Society Consensus Panel

              Abstract Aims To appraise the clinical and genetic evidence that low-density lipoproteins (LDLs) cause atherosclerotic cardiovascular disease (ASCVD). Methods and results We assessed whether the association between LDL and ASCVD fulfils the criteria for causality by evaluating the totality of evidence from genetic studies, prospective epidemiologic cohort studies, Mendelian randomization studies, and randomized trials of LDL-lowering therapies. In clinical studies, plasma LDL burden is usually estimated by determination of plasma LDL cholesterol level (LDL-C). Rare genetic mutations that cause reduced LDL receptor function lead to markedly higher LDL-C and a dose-dependent increase in the risk of ASCVD, whereas rare variants leading to lower LDL-C are associated with a correspondingly lower risk of ASCVD. Separate meta-analyses of over 200 prospective cohort studies, Mendelian randomization studies, and randomized trials including more than 2 million participants with over 20 million person-years of follow-up and over 150 000 cardiovascular events demonstrate a remarkably consistent dose-dependent log-linear association between the absolute magnitude of exposure of the vasculature to LDL-C and the risk of ASCVD; and this effect appears to increase with increasing duration of exposure to LDL-C. Both the naturally randomized genetic studies and the randomized intervention trials consistently demonstrate that any mechanism of lowering plasma LDL particle concentration should reduce the risk of ASCVD events proportional to the absolute reduction in LDL-C and the cumulative duration of exposure to lower LDL-C, provided that the achieved reduction in LDL-C is concordant with the reduction in LDL particle number and that there are no competing deleterious off-target effects. Conclusion Consistent evidence from numerous and multiple different types of clinical and genetic studies unequivocally establishes that LDL causes ASCVD.
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                Author and article information

                Journal
                Eur Heart J Qual Care Clin Outcomes
                Eur Heart J Qual Care Clin Outcomes
                ehjqcco
                European Heart Journal. Quality of Care & Clinical Outcomes
                Oxford University Press
                2058-5225
                2058-1742
                January 2022
                16 October 2020
                16 October 2020
                : 8
                : 1
                : 31-38
                Affiliations
                [1 ] Department of Cardiology, Medical Director Charité Cardiovascular Center (CC11), Campus Benjamin Franklin Charité – Universitätsmedizin Berlin , Hindenburgdamm 30, 12203, Berlin, Germany
                [2 ] Department of Learning, Informatics, Management and Ethics, Karolinska Institutet , 171 77, Stockholm, Sweden
                [3 ] Managing Director, The Swedish Institute for Health Economics , Box 2127, 220 02, Lund, Sweden
                [4 ] Department of Medical Sciences, Cardiology, Uppsala University , 751 85, Uppsala, Sweden
                [5 ] School of Health and Related Research, University of Sheffield , 30 Regent St, Sheffield, S1 4DA
                [6 ] Global Health Economics, Amgen (Europe) GmbH , Suurstoffi 22, 6343, Rotkreuz, Switzerland
                [7 ] Global Health Economics, Amgen Inc, 1 Amgen Center Drive , Thousand Oaks, CA, 91320, USA
                [8 ] Medical Affairs, Amgen AB , Gustav III: s Boulevard 54, 169 74, Solna, Sweden
                [9 ] Department of Medical Sciences, Uppsala University , 751 85, Uppsala, Sweden
                [10 ] Medical Affairs, Amgen (Europe) GmbH , Suurstoffi 22, 6343, Rotkreuz, Switzerland
                [11 ] Division of Cardiology, University of California Los Angeles, 10833 LeConte Avenue , Los Angeles, CA, 90095, USA
                Author notes
                Corresponding author. Tel: +49-(30) 450 513 702, Email: ulf.landmesser@ 123456charite.de
                Author information
                https://orcid.org/0000-0002-0214-3203
                Article
                qcaa072
                10.1093/ehjqcco/qcaa072
                8728027
                33063111
                d69ac6d3-7871-40fb-aa8b-2fb9b5fbf8ff
                © The Author(s) 2020. Published by Oxford University Press on behalf of the European Society of Cardiology.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com

                History
                : 19 May 2020
                : 27 July 2020
                : 30 September 2020
                : 31 August 2020
                Page count
                Pages: 8
                Funding
                Funded by: Amgen, DOI 10.13039/100002429;
                Categories
                Original Article
                AcademicSubjects/MED00200

                cost-effectiveness,evolocumab,low-density lipoprotein cholesterol,myocardial infarction,pcsk9 inhibitors,statins

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