Cost-utility analysis of evolocumab in patients with ASCVD in Italy

Authors

  • Andrea Marcellusi Faculty of Economics, Economic Evaluation and HTA (EEHTA), CEIS, University of Rome “Tor Vergata”, Rome - Italy and Institute for Leadership and Management in Health - Kingston University London, London - UK
  • Chiara Bini Faculty of Economics, Economic Evaluation and HTA (EEHTA), CEIS, University of Rome “Tor Vergata”, Rome - Italy
  • Maria Assunta Rotundo Faculty of Economics, Economic Evaluation and HTA (EEHTA), CEIS, University of Rome “Tor Vergata”, Rome - Italy
  • Emanuela Arcangeli Value & Access Department Italy, Amgen Srl, Milan - Italy
  • Laura Martinez AMGEN Europe, Rotkreuz - Switzerland
  • Francesc Sorio Vilela AMGEN Europe, Rotkreuz - Switzerland
  • Francesco Saverio Mennini Faculty of Economics, Economic Evaluation and HTA (EEHTA), CEIS, University of Rome “Tor Vergata”, Rome - Italy and Institute for Leadership and Management in Health - Kingston University London, London - UK

DOI:

https://doi.org/10.33393/grhta.2021.2255

Keywords:

Cardiovascular disease, PCSK9 inhibitors

Abstract

Objective: The aim of this work was to evaluate the cost-effectiveness of evolocumab in addition to standard statin therapy with or without ezetimibe in the treatment of patients with clinically evident atherosclerotic cardiovascular disease (ASCVD) with levels of LDL-C above 100 mg/dL.

Method: A theoretical cohort of patients was forecast by a Markov model that includes 11 health states for a lifetime horizon. In the base-case, the standard therapy was characterized by statins with or without ezetimibe. Two sub-populations have been considered, Recent MI (Myocardial Infarction in the last year) and Multiple events (population with multiple MI). The results were also presented for a subset of the Multiple events populations consisting of patients who have experienced a myocardial infarction (MI) in the last year.

Results: For the Recent MI and Multiple events populations, ICER values of € 39,547 and € 35,744 respectively were estimated. The value of ICER was lower for the Multiple events with MI < 1 year population (€ 29,949). Considering statins with ezetimibe as standard therapy, ICER values were found to be equal to € 39,781, € 35,986 and € 30,190 respectively for the populations Recent MI, Multiple events and Multiple events with MI < 1 year.

Conclusions: The estimated ICER values for the Recent MI, Multiple events and Multiple events populations with MI < 1 year were below the cost-effectiveness threshold of € 40,000, suggesting therefore how the treatment with evolocumab in addition to the standard therapy can be a cost-effective treatment both compared to standard therapy with statins and standard therapy with statins + ezetimibe.

References

Bhatnagar D, Soran H, Durrington PN. Hypercholesterolaemia and its management. BMJ. 2008;337(aug21 1):a993. https://doi.org/10.1136/bmj.a993 PMID:18719012 DOI: https://doi.org/10.1136/bmj.a993

Roth GA, Fihn SD, Mokdad AH, Aekplakorn W, Hasegawa T, Lim SS. High total serum cholesterol, medication coverage and therapeutic control: an analysis of national health examination survey data from eight countries. Bull World Health Organ. 2011;89(2):92-101. https://doi.org/10.2471/BLT.10.079947 PMID:21346920 DOI: https://doi.org/10.2471/BLT.10.079947

Catapano AL, Graham I, De Backer G, et al; ESC Scientific Document Group. 2016 ESC/EAS Guidelines for the Management of Dyslipidaemias. Eur Heart J. 2016;37(39):2999-3058. https://doi.org/10.1093/eurheartj/ehw272 PMID:27567407 DOI: https://doi.org/10.1093/eurheartj/ehw272

Landmesser U, Chapman MJ, Farnier M, et al; European Society of Cardiology (ESC); European Atherosclerosis Society (EAS). European Society of Cardiology/European Atherosclerosis Society Task Force consensus statement on proprotein convertase subtilisin/kexin type 9 inhibitors: practical guidance for use in patients at very high cardiovascular risk. Eur Heart J. 2017;38(29):2245-2255. PMID:27789571 DOI: https://doi.org/10.1093/eurheartj/ehw480

Goldstein JL, Brown MS. A century of cholesterol and coronaries: from plaques to genes to statins. Cell. 2015;161(1):161-172. https://doi.org/10.1016/j.cell.2015.01.036 PMID:25815993 DOI: https://doi.org/10.1016/j.cell.2015.01.036

Ference BA, Ginsberg HN, Graham I, et al. 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. Eur Heart J. 2017;38(32):2459-2472. https://doi.org/10.1093/eurheartj/ehx144 PMID:28444290 DOI: https://doi.org/10.1093/eurheartj/ehx144

Benjamin EJ, Blaha MJ, Chiuve SE, et al; American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Heart Disease and Stroke Statistics-2017 Update: A Report From the American Heart Association. Circulation. 2017;135(10):e146-e603. https://doi.org/10.1161/CIR.0000000000000485 PMID:28122885 DOI: https://doi.org/10.1161/CIR.0000000000000491

Davis KL, Meyers J, Zhao Z, McCollam PL, Murakami M. High-Risk Atherosclerotic Cardiovascular Disease in a Real-World Employed Japanese Population: Prevalence, Cardiovascular Event Rates, and Costs. J Atheroscler Thromb. 2015;22(12):1287-1304. https://doi.org/10.5551/jat.28852 PMID:26289083 DOI: https://doi.org/10.5551/jat.28852

Henk HJ, Paoli CJ, Gandra SR. A Retrospective Study to Examine Healthcare Costs Related to Cardiovascular Events in Individuals with Hyperlipidemia. Adv Ther. 2015;32(11):1104-1116. https://doi.org/10.1007/s12325-015-0264-7 PMID:26585336 DOI: https://doi.org/10.1007/s12325-015-0264-7

Jernberg T, Hasvold P, Henriksson M, Hjelm H, Thuresson M, Janzon M. Cardiovascular risk in post-myocardial infarction patients: nationwide real world data demonstrate the importance of a long-term perspective. Eur Heart J. 2015;36(19):1163-1170. https://doi.org/10.1093/eurheartj/ehu505 PMID:25586123 DOI: https://doi.org/10.1093/eurheartj/ehu505

Punekar RS, Fox KM, Richhariya A, et al. Burden of First and Recurrent Cardiovascular Events Among Patients With Hyperlipidemia. Clin Cardiol. 2015;38(8):483-491. https://doi.org/10.1002/clc.22428 PMID:26100722 DOI: https://doi.org/10.1002/clc.22428

Hallberg S, Gandra SR, Fox KM, et al. Healthcare costs associated with cardiovascular events in patients with hyperlipidemia or prior cardiovascular events: estimates from Swedish population-based register data. Eur J Health Econ. 2016;17(5):591-601. https://doi.org/10.1007/s10198-015-0702-0 PMID:26077550 DOI: https://doi.org/10.1007/s10198-015-0702-0

Toth PP, Danese M, Villa G, et al. Estimated burden of cardiovascular disease and value-based price range for evolocumab in a high-risk, secondary-prevention population in the US payer context. J Med Econ. 2017;20(6):555-564. https://doi.org/10.1080/13696998.2017.1284078PMID:28097904 DOI: https://doi.org/10.1080/13696998.2017.1284078

Baigent C, Blackwell L, Emberson J, et al; Cholesterol Treatment Trialists’ (CTT) Collaboration. Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials. Lancet. 2010;376(9753):1670-1681. https://doi.org/10.1016/S0140-6736(10)61350-5 PMID:21067804 DOI: https://doi.org/10.1016/S0140-6736(10)61350-5

Cannon CP, Blazing MA, Giugliano RP, et al; IMPROVE-IT Investigators. Ezetimibe Added to Statin Therapy after Acute Coronary Syndromes. N Engl J Med. 2015;372(25):2387-2397. https://doi.org/10.1056/NEJMoa1410489 PMID:26039521 DOI: https://doi.org/10.1056/NEJMoa1410489

Zetia US Prescribing information. May 16, 2015; Online http://www.merck.com/product/usa/pi_circulars/z/zetia/zetia_pi.pdf (Accessed July 2021)

Merck Sharp and Dohme Limited. Ezetrol 10 mg Tablets. Summary of product characteristics 2012. May 16, 2017]; Online https://www.medicines.org.uk/emc/medicine/12091/SPC/Ezetrol+10mg+Tablets/. (Accessed July 2021)

Stone NJ, Robinson JG, Lichtenstein AH, et al; American College of Cardiology/American Heart Association Task Force on Practice Guidelines. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2014;129(25)(suppl 2):S1-S45. https://doi.org/10.1161/01.cir.0000437738.63853.7aPMID:24222016

Mach F, Baigent C, Catapano AL, et al; ESC Scientific Document Group. 2019 ESC/EAS Guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk. Eur Heart J. 2020;41(1):111-188. https://doi.org/10.1093/eurheartj/ehz455 PMID:31504418 DOI: https://doi.org/10.1093/eurheartj/ehz455

Wei CY, Quek RGW, Villa G, et al. A systematic review of cardiovascular outcomes-based cost-effectiveness analyses of lipid-lowering therapies. Pharmacoeconomics. 2017;35(3):297-318. https://doi.org/10.1007/s40273-016-0464-2 . PMID: 27785772. DOI: https://doi.org/10.1007/s40273-016-0464-2

Peng W, Qiang F, Peng W, et al. Therapeutic efficacy of PCSK9 monoclonal antibodies in statin-nonresponsive patients with hypercholesterolemia and dyslipidemia: A systematic review and meta-analysis. Int J Cardiol. 2016;222:119-129. https://doi.org/10.1016/j.ijcard.2016.07.239PMID:27494723 DOI: https://doi.org/10.1016/j.ijcard.2016.07.239

Gouni-Berthold I, Descamps OS, Fraass U, et al. Systematic review of published Phase 3 data on anti-PCSK9 monoclonal antibodies in patients with hypercholesterolaemia. Br J Clin Pharmacol. 2016;82(6):1412-1443. https://doi.org/10.1111/bcp.13066 PMID:27478094 DOI: https://doi.org/10.1111/bcp.13066

Navarese EP, Kolodziejczak M, Schulze V, et al. Effects of proprotein convertase subtilisin/kexin type 9 antibodies in adults with hypercholesterolemia: A systematic review and meta-analysis. Ann Intern Med. 2015;163(1):40-51. https://doi.org/10.7326/M14-2957PMID:25915661 DOI: https://doi.org/10.7326/M14-2957

Sabatine MS, Giugliano RP, Keech A, et al. Rationale and design of the Further cardiovascular OUtcomes Research with PCSK9 Inhibition in subjects with Elevated Risk trial. Am Heart J. 2016;173:94-101. https://doi.org/10.1016/j.ahj.2015.11.015 PMID:26920601 DOI: https://doi.org/10.1016/j.ahj.2015.11.015

Gandra SR, Villa G, Fonarow GC, et al. Cost-Effectiveness of LDL-C Lowering With Evolocumab in Patients With High Cardiovascular Risk in the United States. Clin Cardiol. 2016;39(6):313-320. https://doi.org/10.1002/clc.22535 PMID:27092712 DOI: https://doi.org/10.1002/clc.22535

Villa G, Lothgren M, Kutikova L, et al. Cost-effectiveness of Evolocumab in Patients With High Cardiovascular Risk in Spain. Clin Ther. 2017;39(4):771-786.e3. https://doi.org/10.1016/j.clinthera.2017.02.011 PMID:28366593 DOI: https://doi.org/10.1016/j.clinthera.2017.02.011

Fonarow GC, Keech AC, Pedersen TR, et al. Cost-effectiveness of Evolocumab Therapy for Reducing Cardiovascular Events in Patients With Atherosclerotic Cardiovascular Disease. JAMA Cardiol. 2017;2(10):1069-1078. https://doi.org/10.1001/jamacardio.2017.2762 PMID:28832867 DOI: https://doi.org/10.1001/jamacardio.2017.2762

Borissov B, Urbich M, Georgieva B, Tsenov S, Villa G. Cost-effectiveness of evolocumab in treatment of heterozygous familial hypercholesterolaemia in Bulgaria: measuring health benefit by effectively treated patient-years. J Mark Access Health Policy. 2017;5(1):1412753. https://doi.org/10.1080/20016689.2017.1412753 PMID:29321830 DOI: https://doi.org/10.1080/20016689.2017.1412753

Fonarow GC, van Hout B, Villa G, Arellano J, Lindgren P. Updated Cost-effectiveness Analysis of Evolocumab in Patients With Very High-risk Atherosclerotic Cardiovascular Disease. JAMA Cardiol. 2019;4(7):691-695. https://doi.org/10.1001/jamacardio.2019.1647PMID:31166576 DOI: https://doi.org/10.1001/jamacardio.2019.1647

Lindh M, Banefelt J, Fox KM, et al. Cardiovascular event rates in a high atherosclerotic cardiovascular disease risk population: estimates from Swedish population-based register data. Eur Heart J Qual Care Clin Outcomes. 2019;5(3):225-232. https://doi.org/10.1093/ehjqcco/qcy058 PMID:30649251 DOI: https://doi.org/10.1093/ehjqcco/qcy058

Landmesser U, Lindgren P, Hagström E, et al. Cost-effectiveness of PCSK9 inhibition with evolocumab in patients with a history of myocardial infarction in Sweden. Eur Heart J Qual Care Clin Outcomes. 2020;qcaa072. https://doi.org/10.1093/ehjqcco/qcaa072 PMID:33063111 DOI: https://doi.org/10.1093/ehjqcco/qcaa072

Nuijten MJ, Pronk MH, Brorens MJ, et al. Reporting format for economic evaluation. Part II: focus on modelling studies. PharmacoEconomics. 1998;14(3):259-268. https://doi.org/10.2165/00019053-199814030-00003 PMID:10186465 DOI: https://doi.org/10.2165/00019053-199814030-00003

Ara R, Basarir H, Ward SE. Principles of health economic evaluations of lipid-lowering strategies. Curr Opin Lipidol. 2012;23(4):271-281. https://doi.org/10.1097/MOL.0b013e32835423d9 PMID:22617753 DOI: https://doi.org/10.1097/MOL.0b013e32835423d9

Ara R and Brazier J. Health related quality of life by age, gender and history of cardiovascular disease: results from the Health Survey for England. HEDS Discussion Paper. (2017). Online http://eprints.whiterose.ac.uk/10880/1/HEDS_DP_09-12.pdf.

Gray AM. Applied Methods of Cost-effectiveness Analysis in Healthcare. Oxford. Oxford University Press; 2010.

Sciattella P, et al. Rehospitalization due to Cardiovascular Events in Secondary Prevention Patients Treated with Lipid-Lowering Therapies in Italy. In: ISPOR Europe. Denmark: Copenaghen; 2019. https://doi.org/10.1016/j.jval.2019.09.808 DOI: https://doi.org/10.1016/j.jval.2019.09.808

Degli Esposti et al. Ipercolesterolemie familiari e pazienti a rischio cardiovascolare molto alto: analisi dei Real World Data. GIHTAD; 2016;9:2. Online https://springerhealthcare.it/GIHTAD/2016/08/02/introduzione/ (Accessed July 2021)

Hagström E et al., Rates of major cardiovascular events in patients with a history of myocardial infarction and additional cardiovascular risk factors: evidence from a Swedish nationwide register-based study. Value in Health, 23, S488–S489. https://doi.org/10.1016/j.jval.2020.08.506 DOI: https://doi.org/10.1016/j.jval.2020.08.506

ISTAT. Tavole di mortalità 2019. Online http://demo.istat.it/tvm2016/index.php?lingua=ita. (Accessed July 2021)

Instituto Nacional de Estadística. Tablas de mortalidad. Madrid; 2015. https://www.ine.es/jaxiT3/Tabla.htm?t=27154 (Accessed July 2021)

LaRosa JC, Grundy SM, Waters DD, et al; Treating to New Targets (TNT) Investigators. Intensive lipid lowering with atorvastatin in patients with stable coronary disease. N Engl J Med. 2005;352(14):1425-1435. https://doi.org/10.1056/NEJMoa050461 PMID:15755765 DOI: https://doi.org/10.1056/NEJMoa050461

Law MR, Wald NJ, Thompson SG. By how much and how quickly does reduction in serum cholesterol concentration lower risk of ischaemic heart disease? BMJ. 1994;308(6925):367-372. https://doi.org/10.1136/bmj.308.6925.367 PMID:8043072 DOI: https://doi.org/10.1136/bmj.308.6925.367

Gould AL, Rossouw JE, Santanello NC, Heyse JF, Furberg CD. Cholesterol reduction yields clinical benefit: impact of statin trials. Circulation. 1998;97(10):946-952. https://doi.org/10.1161/01.CIR.97.10.946 PMID:9529261 DOI: https://doi.org/10.1161/01.CIR.97.10.946

Robinson JG, Smith B, Maheshwari N, Schrott H. Pleiotropic effects of statins: benefit beyond cholesterol reduction? A meta-regression analysis. J Am Coll Cardiol. 2005;46(10):1855-1862. https://doi.org/10.1016/j.jacc.2005.05.085 PMID:16286171 DOI: https://doi.org/10.1016/j.jacc.2005.05.085

Collins R, Reith C, Emberson J, et al. Interpretation of the evidence for the efficacy and safety of statin therapy. Lancet. 2016;388(10059):2532-2561. https://doi.org/10.1016/S0140-6736(16)31357-5 PMID:27616593 DOI: https://doi.org/10.1016/S0140-6736(16)31357-5

Buchwald H, Varco RL, Matts JP, et al. Effect of partial ileal bypass surgery on mortality and morbidity from coronary heart disease in patients with hypercholesterolemia. Report of the Program on the Surgical Control of the Hyperlipidemias (POSCH). N Engl J Med. 1990;323(14):946-955. https://doi.org/10.1056/NEJM199010043231404 PMID:2205799 DOI: https://doi.org/10.1056/NEJM199010043231404

Frick MH, Elo O, Haapa K, et al. Helsinki Heart Study: primary-prevention trial with gemfibrozil in middle-aged men with dyslipidemia. Safety of treatment, changes in risk factors, and incidence of coronary heart disease. N Engl J Med. 1987;317(20):1237-1245. https://doi.org/10.1056/NEJM198711123172001 PMID:3313041 DOI: https://doi.org/10.1056/NEJM198711123172001

Ference BA, Robinson JG, Brook RD, et al. Variation in PCSK9 and HMGCR and Risk of Cardiovascular Disease and Diabetes. N Engl J Med. 2016;375(22):2144-2153. https://doi.org/10.1056/NEJMoa1604304 PMID:27959767 DOI: https://doi.org/10.1056/NEJMoa1604304

Koren, MJ et al., Final report of the OSLER-1 study. Long-term evoloculab for the treatment of hypercholesterolemia. Journal of the American College of Cardiology, 2019;74(17): 2132–2146. https://doi.org/10.1016/j.jacc.2019.08.1024 DOI: https://doi.org/10.1016/j.jacc.2019.08.1024

Matza LS, Stewart KD, Gandra SR, et al. Acute and chronic impact of cardiovascular events on health state utilities. BMC Health Serv Res. 2015;15(1):173. https://doi.org/10.1186/s12913-015-0772-9 PMID:25896804 DOI: https://doi.org/10.1186/s12913-015-0772-9

Tengs TO, Yu M, Luistro E. Health-related quality of life after stroke a comprehensive review. Stroke. 2001;32(4):964-972. https://doi.org/10.1161/01.STR.32.4.964 PMID:11283398 DOI: https://doi.org/10.1161/01.STR.32.4.964

Cesaro A, Gragnano F, Fimiani F, et al. Impact of PCSK9 inhibitors on the quality of life of patients at high cardiovascular risk. Eur J Prev Cardiol. 2020;27(5):556-558. https://doi.org/10.1177/2047487319839179 PMID:30913901 DOI: https://doi.org/10.1177/2047487319839179

AIFA. Liste di trasparenza. 2018; Online https://www.aifa.gov.it/liste-di-trasparenza.

Farmadati Italia S.R.L. 2018; Online https://www.farmadati.it/.

Associazione Italiana Economia Sanitaria (AIES). Proposta di Linee-Guida per la valutazione economica degli interventi sanitari. Poilitiche Sanitarie. 2009;10(2):91-99.

Henry CA, Lyon RA, Ling H. Clinical efficacy and safety of evolocumab for low-density lipoprotein cholesterol reduction. Vasc Health Risk Manag. 2016;12:163-169. PMID:27143910 DOI: https://doi.org/10.2147/VHRM.S82387

Krähenbühl S, Pavik-Mezzour I, von Eckardstein A. Unmet Needs in LDL-C Lowering: When Statins Won’t Do! Drugs. 2016;76(12):1175-1190. https://doi.org/10.1007/s40265-016-0613-0PMID:27456066 DOI: https://doi.org/10.1007/s40265-016-0613-0

AIM-HIGH Investigators, Boden WE, Probstfield JL, et al. Niacin in patients with low HDL cholesterol levels receiving intensive statin therapy. N Engl J Med. 2011;365(24):2255-67. https://doi.org/10.1056/NEJMoa1107579 . PMID: 22085343. DOI: https://doi.org/10.1056/NEJMoa1107579

Brugts JJ, Yetgin T, Hoeks SE, et al. The benefits of statins in people without established cardiovascular disease but with cardiovascular risk factors: meta-analysis of randomised controlled trials. BMJ. 2009;338(jun30 1):b2376. https://doi.org/10.1136/bmj.b2376PMID:19567909 DOI: https://doi.org/10.1136/bmj.b2376

Janković SM, Tešić D, Anđelković J, Kostić M. Profile of evolocumab and its cost-effectiveness in patients with high cardiovascular risk: literature review. Expert Rev Pharmacoecon Outcomes Res. 2018;18(5):461-474. https://doi.org/10.1080/14737167.2018.1501679 PMID:30014724 DOI: https://doi.org/10.1080/14737167.2018.1501679

Kiortsis DN, Giral P, Bruckert E, Turpin G. Factors associated with low compliance with lipid-lowering drugs in hyperlipidemic patients. J Clin Pharm Ther. 2000;25(6):445-451. https://doi.org/10.1046/j.1365-2710.2000.00315.x PMID:11123498 DOI: https://doi.org/10.1046/j.1365-2710.2000.00315.x

Mennini FS, Bianic F, Baio G, et al. Estimating The Cost-Effectiveness Profile Of A Vaccination Programme With A Nine-Valent Hpv Vaccine In Italy. Value Health. 2015;18(7):A457. https://doi.org/10.1016/j.jval.2015.09.1171 DOI: https://doi.org/10.1016/j.jval.2015.09.1171

Mennini FS, Costa S, Favato G, Picardo M. Anti-HPV vaccination: a review of recent economic data for Italy. Vaccine. 2009;27(suppl 1):A54-A61. https://doi.org/10.1016/j.vaccine.2009.02.052 PMID:19480963 DOI: https://doi.org/10.1016/j.vaccine.2009.02.052

Danese MD, Permbergon-Ross P, Catterick D, Villa G. Estimation of the increased risk associated with recurrent events or polyvascular atherosclerotic cardiovascular disease in the United Kingdom. Eur J Prev Cardiol. 2020;28(3):335–343. https://doi.org/10.1177/2047487319899212 PMID: 31964187 DOI: https://doi.org/10.1177/2047487319899212

Brahmer J, Reckamp KL, Baas P, et al. Nivolumab versus Docetaxel in Advanced Squamous-Cell Non-Small-Cell Lung Cancer. N Engl J Med. 2015;373(2):123-35. https://doi.org/10.1056/NEJMoa1504627 . PMID: 26028407 DOI: https://doi.org/10.1056/NEJMoa1504627

Published

2021-11-02

How to Cite

1.
Marcellusi A, Bini C, Rotundo MA, Arcangeli E, Martinez L, Sorio Vilela F, Mennini FS. Cost-utility analysis of evolocumab in patients with ASCVD in Italy. Grhta [Internet]. 2021 Nov. 2 [cited 2021 Dec. 7];8:155-67. Available from: https://journals.aboutscience.eu/index.php/grhta/article/view/2255

Issue

Section

Original Research Article

Most read articles by the same author(s)