Cost-effectiveness of lipid lowering with statins and ezetimibe in chronic kidney disease

Iryna Schlackow, Seamus Kent, William Herrington, Jonathan Emberson, Richard Haynes, Christina Reith, Rory Collins, Martin J Landray, Alastair Gray, Colin Baigent, Borislava Mihaylova, SHARP Collaborative Group, R Collins, C Baigent, M J Landray, C Bray, Y Chen, A Baxter, A Young, M Hill, C Knott, A Cass, B Feldt-Rasmussen, B Fellström, D E Grobbee, C Grönhagen-Riska, M Haas, H Holdaas, L S Hooi, L Jiang, B Kasiske, U Krairittichai, A Levin, Z A Massy, V Tesar, R Walker, C Wanner, D C Wheeler, A Wiecek, T Dasgupta, W Herrington, D Lewis, M Mafham, W Majoni, C Reith, J Emberson, S Parish, D Simpson, J Strony, T Musliner, L Agodoa, J Armitage, Z Chen, J Craig, D de Zeeuw, J M Gaziano, R Grimm, V Krane, B Neal, V Ophascharoensuk, T Pedersen, P Sleight, J Tobert, C Tomson, Iryna Schlackow, Seamus Kent, William Herrington, Jonathan Emberson, Richard Haynes, Christina Reith, Rory Collins, Martin J Landray, Alastair Gray, Colin Baigent, Borislava Mihaylova, SHARP Collaborative Group, R Collins, C Baigent, M J Landray, C Bray, Y Chen, A Baxter, A Young, M Hill, C Knott, A Cass, B Feldt-Rasmussen, B Fellström, D E Grobbee, C Grönhagen-Riska, M Haas, H Holdaas, L S Hooi, L Jiang, B Kasiske, U Krairittichai, A Levin, Z A Massy, V Tesar, R Walker, C Wanner, D C Wheeler, A Wiecek, T Dasgupta, W Herrington, D Lewis, M Mafham, W Majoni, C Reith, J Emberson, S Parish, D Simpson, J Strony, T Musliner, L Agodoa, J Armitage, Z Chen, J Craig, D de Zeeuw, J M Gaziano, R Grimm, V Krane, B Neal, V Ophascharoensuk, T Pedersen, P Sleight, J Tobert, C Tomson

Abstract

Statin-based treatments reduce cardiovascular disease (CVD) risk in patients with non-dialysis chronic kidney disease (CKD), but it is unclear which regimen is the most cost-effective. We used the Study of Heart and Renal Protection (SHARP) CKD-CVD policy model to evaluate the effect of statins and ezetimibe on quality-adjusted life years (QALYs) and health care costs in the United States (US) and the United Kingdom (UK). Net costs below $100,000/QALY (US) or £20,000/QALY (UK) were considered cost-effective. We investigated statin regimens with or without ezetimibe 10 mg. Treatment effects on cardiovascular risk were estimated per 1-mmol/L reduction in low-density lipoprotein (LDL) cholesterol as reported in the Cholesterol Treatment Trialists' Collaboration meta-analysis, and reductions in LDL cholesterol were estimated for each statin/ezetimibe regimen. In the US, atorvastatin 40 mg ($0.103/day as of January 2019) increased life expectancy by 0.23 to 0.31 QALYs in non-dialysis patients with stages 3B to 5 CKD, at a net cost of $20,300 to $78,200/QALY. Adding ezetimibe 10 mg ($0.203/day) increased life expectancy by an additional 0.05 to 0.07 QALYs, at a net cost of $43,600 to $91,500/QALY. The cost-effectiveness findings and policy implications in the UK were similar. In summary, in patients with non-dialysis-dependent CKD, the evidence suggests that statin/ezetimibe combination therapy is a cost-effective treatment to reduce the risk of CVD.

Trial registration: ClinicalTrials.gov NCT00125593.

Keywords: chronic kidney disease; cost-effectiveness; ezetimibe; health care costs; quality-adjusted life years; statin.

Copyright © 2019 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

Figures

Graphical abstract
Graphical abstract
Figure 1
Figure 1
Probability of a statin-based treatment to be cost-effective in moderate-to-advanced nondialysis chronic kidney disease (CKD) patients. Results shown for treatments on the cost-effectiveness frontier (i.e., the most cost-effective treatment for a given value of willingness to pay) within the range of willingness-to-pay values per quality-adjusted life-year (QALY). Typical cost-effectiveness thresholds are represented with dashed horizontal lines. Atorvastatin 20 mg daily was largely dominated by atorvastatin 40 mg daily and was omitted from the graph. LDL-C, low-density lipoprotein cholesterol; UK, United Kingdom; US, United States.
Figure 2
Figure 2
Cost-effectiveness of adding ezetimibe 10 mg to atorvastatin 40 mg daily for moderate-to-advanced nondialysis chronic kidney disease (CKD) patients, at different ezetimibe cost. The CKD and cardiovascular risk categories are derived directly from the 6235 moderate-to-advanced non–dialysis-dependent CKD patients in the Study of Heart and Renal Protection (SHARP). Typical cost-effectiveness thresholds are represented with dashed horizontal lines. *A total of 338 (17%) participants with CKD stage 3A (estimated glomerular filtration rate [eGFR] 60–45 ml/min per 1.73 m2). At the $100,000/quality-adjusted life-year [QALY] threshold in the United States (US) (a), ezetimibe 10 mg daily becomes cost-effective in all categories of patients when its price reaches $0.323/d. At the £20,000/QALY threshold in the United Kingdom (UK) (b), ezetimibe 10 mg daily becomes cost-effective in all categories of patients when its price reaches £0.019/d.

References

    1. GBD 2016 Disease and Injury Incidence and Prevalence Collaborators Global, regional, and national incidence, prevalence, and years lived with disability for 328 diseases and injuries for 195 countries, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet. 2017;390:1211–1259.
    1. GBD 2016 Causes of Death Collaborators Global, regional, and national age-sex specific mortality for 264 causes of death, 1980-2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet. 2017;390:1151–1210.
    1. United States Renal Data System . National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases; Bethesda, MD: 2017. 2017 USRDS annual data report: Epidemiology of kidney disease in the United States.
    1. Chronic Kidney Disease Prognosis Consortium. Matsushita K., van der Velde M. Association of estimated glomerular filtration rate and albuminuria with all-cause and cardiovascular mortality in general population cohorts: a collaborative meta-analysis. Lancet. 2010;375:2073–2081.
    1. Go A.S., Chertow G.M., Fan D., McCulloch C.E., Hsu C.Y. Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization. N Engl J Med. 2004;351:1296–1305.
    1. Baigent C., Landray M.J., Reith C. The effects of lowering LDL cholesterol with simvastatin plus ezetimibe in patients with chronic kidney disease (Study of Heart and Renal Protection): a randomised placebo-controlled trial. Lancet. 2011;377:2181–2192.
    1. Cholesterol Treatment Trialists' (CTT) Collaboration Impact of renal function on the effects of LDL cholesterol lowering with statin-based regimens: a meta-analysis of individual participant data from 28 randomised trials. Lancet Diabetes Endocrinol. 2016;4:829–839.
    1. Cannon C.P., Blazing M.A., Giugliano R.P. Ezetimibe added to statin therapy after acute coronary syndromes. N Engl J Med. 2015;372:2387–2397.
    1. 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;376:1670–1681.
    1. Wanner C., Tonelli M., Kidney Disease Improving Global Outcomes Lipid Guideline Development Work Group M. KDIGO clinical practice guideline for lipid management in CKD: summary of recommendation statements and clinical approach to the patient. Kidney Int. 2014;85:1303–1309.
    1. Grundy S.M., Stone N.J., Bailey A.L. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. 2018 pii S0735-1097:39034-X.
    1. Goff D.C., Jr., Lloyd-Jones D.M., Bennett G. 2013 ACC/AHA guideline on the assessment of cardiovascular risk: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2014;129:S49–S73.
    1. Stone N.J., Robinson J.G., Lichtenstein A.H. 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:S1–S45.
    1. National Clinical Guideline Centre (UK). Lipid Modification: Cardiovascular Risk Assessment and the Modification of Blood Lipids for the Primary and Secondary Prevention of Cardiovascular Disease. NICE Clinical Guidelines, No. 181. In: London: National Institute for Health and Care Excellence (UK); 2014.
    1. National Institute for Health and Care Excellence (UK) Ezetimibe for treating primary heterozygous-familial and non-familial hypercholesterolaemia. Technology appraisal guidance (TA385) Available at:
    1. Mihaylova B., Schlackow I., Herrington W. Cost-effectiveness of simvastatin plus ezetimibe for cardiovascular prevention in CKD: results of the Study of Heart and Renal Protection (SHARP) Am J Kidney Dis. 2016;67:576–584.
    1. Schlackow I., Kent S., Herrington W. A policy model of cardiovascular disease in moderate-to-advanced chronic kidney disease. Heart. 2017;103:1880–1890.
    1. SHARP Collaborative Group Study of Heart and Renal Protection (SHARP): randomized trial to assess the effects of lowering low-density lipoprotein cholesterol among 9,438 patients with chronic kidney disease. Am Heart J. 2010;160:785–794.
    1. Heart Protection Study Collaborative Group Lifetime cost effectiveness of simvastatin in a range of risk groups and age groups derived from a randomised trial of 20,536 people. BMJ. 2006;333:1145.
    1. Heart Protection Study Collaborative Group Cost-effectiveness of simvastatin in people at different levels of vascular disease risk: economic analysis of a randomised trial in 20,536 individuals. Lancet. 2005;365:1779–1785.
    1. Erickson K.F., Japa S., Owens D.K., Chertow G.M., Garber A.M., Goldhaber-Fiebert J.D. Cost-effectiveness of statins for primary cardiovascular prevention in chronic kidney disease. J Am Coll Cardiol. 2013;61:1250–1258.
    1. Collins R., Reith C., Emberson J. Interpretation of the evidence for the efficacy and safety of statin therapy. Lancet. 2016;388:2532–2561.
    1. Law M., Rudnicka A.R. Statin safety: a systematic review. Am J Cardiol. 2006;97:52C–60C.
    1. Levey A.S., Stevens L.A., Schmid C.H. A new equation to estimate glomerular filtration rate. Ann Intern Med. 2009;150:604–612.
    1. Haynes R., Lewis D., Emberson J. Effects of lowering LDL cholesterol on progression of kidney disease. J Am Soc Nephrol. 2014;25:1825–1833.
    1. Kent S., Schlackow I., Lozano-Kuhne J. What is the impact of chronic kidney disease stage and cardiovascular disease on the annual cost of hospital care in moderate-to-severe kidney disease? BMC Nephrol. 2015;16:65.
    1. Bureau of Labor Statistics Consumer Price Index. 2016. Available at:
    1. Curtis L., Burns A. Unit Costs of Health and Social Care 2015. 2015. Available at:
    1. Centers for Medicare & Medicaid Services National Average Drug Acquisition Cost (NADAC). 2019. Available at:
    1. NHS Prescription Services NHS Electronic Drug Tariff. January 2019. Available at:
    1. Brooks R. EuroQol: the current state of play. Health Policy. 1996;37:53–72.
    1. Shaw J.W., Johnson J.A., Coons S.J. US valuation of the EQ-5D health states: development and testing of the D1 valuation model. Med Care. 2005;43:203–220.
    1. Dolan P. Modeling valuations for EuroQol health states. Med Care. 1997;35:1095–1108.
    1. Sanders G.D., Neumann P.J., Basu A. Recommendations for conduct, methodological practices, and reporting of cost-effectiveness analyses: second panel on cost-effectiveness in health and medicine. JAMA. 2016;316:1093–1103.
    1. The Green Book: appraisal and evaluation in central government. 2013. Available at:
    1. Gray A., Clarke P.M., Wolstenholme J.L., Wordsworth S. Oxford University Press; 2010. Applied Methods of Cost-effectiveness Analysis in Healthcare.
    1. Efron B., Tibshirani R.J. Taylor & Francis; 1994. An Introduction to the Bootstrap.
    1. Briggs A., Claxton K., Sculpher M. Oxford University Press; 2006. Decision Modelling for Health Economic Evaluation.
    1. Pletcher M.J., Lazar L., Bibbins-Domingo K. Comparing impact and cost-effectiveness of primary prevention strategies for lipid-lowering. Ann Intern Med. 2009;150:243–254.
    1. Preiss D., Seshasai S.R., Welsh P. Risk of incident diabetes with intensive-dose compared with moderate-dose statin therapy: a meta-analysis. JAMA. 2011;305:2556–2564.
    1. R: A Language and Environment for Statistical Computing [computer program] R Foundation for Statistical Computing, Vienna, Austria; 2008.
    1. Wickham H. Springer; New York: 2009. ggplot2: Elegant Graphics for Data Analysis.

Source: PubMed

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