Generic placeholder image

Current Vascular Pharmacology

Editor-in-Chief

ISSN (Print): 1570-1611
ISSN (Online): 1875-6212

Review Article

Have We Learnt all from IMPROVE-IT? Part II. Subanalyses of the Effects of Ezetimibe Added to Statin Therapy on Selected Clinical and Laboratory Outcomes, Cost-Effectiveness, Guidelines, and Clinical Implications

Author(s): Zlatko Fras* and Dimitri P. Mikhailidis

Volume 19, Issue 5, 2021

Published on: 27 July, 2020

Page: [469 - 486] Pages: 18

DOI: 10.2174/1570161118999200727230120

Price: $65

Abstract

In this second part of the review of the IMProved Reduction of Outcomes: Vytorin Efficacy International Trial (IMPROVE-IT), the findings in relation to patients with stroke, the ACS phenotype, history of coronary artery bypass graft surgery, heart failure, concurrent polyvascular atherosclerotic cardiovascular disease (ASCVD) and diabetes mellitus, and different levels of expression of selected cardiovascular biomarkers, are discussed. The combination therapy was proven safe, and drug discontinuation rates were not increased by adding ezetimibe. Since both statins and ezetimibe are now almost globally generically available, it can be concluded that for secondary prevention of ASCVD, adding ezetimibe to high-intensity statin therapy further reduces low-density lipoprotein cholesterol (LDL-C) and cardiovascular risk, cost-effectively.

Keywords: IMPROVE-IT trial, ezetimibe, statin, combination lipid-lowering drug therapy, secondary prevention, costeffectiveness, safety, lipid-lowering guidelines.

[1]
Bohula EA, Wiviott SD, Giugliano RP, et al. Prevention of Stroke with the Addition of Ezetimibe to Statin Therapy in Patients With Acute Coronary Syndrome in IMPROVE-IT (Improved Reduction of Outcomes: Vytorin Efficacy International Trial). Circulation 2017; 136(25): 2440-50.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.117.029095] [PMID: 28972004]
[2]
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): 2387-97.
[http://dx.doi.org/10.1056/NEJMoa1410489] [PMID: 26039521]
[3]
Blazing MA, Giugliano RP, de Lemos JA, et al. On-treatment analysis of the Improved Reduction of Outcomes: Vytorin Efficacy International Trial (IMPROVE-IT). Am Heart J 2016; 182: 89-96.
[http://dx.doi.org/10.1016/j.ahj.2016.09.004] [PMID: 27914504]
[4]
De Caterina R, Salvatore T, Marchioli R. Cholesterol-lowering interventions and stroke: Insights from IMPROVE-IT. Atherosclerosis 2016; 248: 216-8.
[http://dx.doi.org/10.1016/j.atherosclerosis.2016.03.024] [PMID: 27035113]
[5]
Pandit AK, Kumar P, Kumar A, Chakravarty K, Misra S, Prasad K. High-dose statin therapy and risk of intracerebral hemorrhage: a meta-analysis. Acta Neurol Scand 2016; 134(1): 22-8.
[http://dx.doi.org/10.1111/ane.12540] [PMID: 26647879]
[6]
Noda H, Iso H, Irie F, et al. Low-density lipoprotein cholesterol concentrations and death due to intraparenchymal hemorrhage: the Ibaraki Prefectural Health Study. Circulation 2009; 119(16): 2136-45.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.108.795666] [PMID: 19364982]
[7]
Yano K, Reed DM, MacLean CJ. Serum cholesterol and hemorrhagic stroke in the Honolulu Heart Program. Stroke 1989; 20(11): 1460-5.
[http://dx.doi.org/10.1161/01.STR.20.11.1460] [PMID: 2815179]
[8]
Wang X, Dong Y, Qi X, Huang C, Hou L. Cholesterol levels and risk of hemorrhagic stroke: a systematic review and meta-analysis. Stroke 2013; 44(7): 1833-9.
[http://dx.doi.org/10.1161/STROKEAHA.113.001326] [PMID: 23704101]
[9]
Ma C, Gurol ME, Huang Z, et al. Low-density lipoprotein cholesterol and risk of intracerebral hemorrhage: A prospective study. Neurology 2019; 93(5): e445-57.
[http://dx.doi.org/10.1212/WNL.0000000000007853] [PMID: 31266905]
[10]
Rist PM, Buring JE, Ridker PM, Kase CS, Kurth T, Rexrode KM. Lipid levels and the risk of hemorrhagic stroke among women. Neurology 2019; 92(19): e2286-94.
[http://dx.doi.org/10.1212/WNL.0000000000007454] [PMID: 30971484]
[11]
Goldstein LB, Amarenco P, Szarek M, et al. SPARCL Investigators Hemorrhagic stroke in the Stroke Prevention by Aggressive Reduction in Cholesterol Levels study. Neurology 2008; 70(24 Pt 2): 2364-70.
[http://dx.doi.org/10.1212/01.wnl.0000296277.63350.77] [PMID: 18077795]
[12]
Amarenco P, Goldstein LB, Szarek M, et al. SPARCL Investigators Effects of intense low-density lipoprotein cholesterol reduction in patients with stroke or transient ischemic attack: the Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trial. Stroke 2007; 38(12): 3198-204.
[http://dx.doi.org/10.1161/STROKEAHA.107.493106] [PMID: 17962589]
[13]
Amarenco P, Labreuche J. Lipid management in the prevention of stroke: review and updated meta-analysis of statins for stroke prevention. Lancet Neurol 2009; 8(5): 453-63.
[http://dx.doi.org/10.1016/S1474-4422(09)70058-4] [PMID: 19375663]
[14]
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): 1670-81.
[http://dx.doi.org/10.1016/S0140-6736(10)61350-5] [PMID: 21067804]
[15]
Kernan WN, Ovbiagele B, Black HR, et al. American Heart Association Stroke Council, Council on Cardiovascular and Stroke Nursing, Council on Clinical Cardiology, and Council on Peripheral Vascular Disease. Guidelines for the prevention of stroke in patients with stroke and transient ischemic attack: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2014; 45(7): 2160-236.
[http://dx.doi.org/10.1161/STR.0000000000000024] [PMID: 24788967]
[16]
Sabatine MS, Giugliano RP, Keech AC, et al. FOURIER Steering Committee and Investigators Evolocumab and Clinical Outcomes in Patients with Cardiovascular Disease. N Engl J Med 2017; 376(18): 1713-22.
[http://dx.doi.org/10.1056/NEJMoa1615664] [PMID: 28304224]
[17]
Giugliano RP, Pedersen TR, Saver JL, et al. FOURIER Investigators Stroke Prevention With the PCSK9 (Proprotein Convertase Subtilisin-Kexin Type 9) Inhibitor Evolocumab Added to Statin in High-Risk Patients With Stable Atherosclerosis. Stroke 2020; 51(5): 1546-54.
[http://dx.doi.org/10.1161/STROKEAHA.119.027759] [PMID: 32312223]
[18]
Schwartz GG, Steg PG, Szarek M, et al. ODYSSEY OUTCOMES Committees and Investigators Alirocumab and Cardiovascular Outcomes after Acute Coronary Syndrome. N Engl J Med 2018; 379(22): 2097-107.
[http://dx.doi.org/10.1056/NEJMoa1801174] [PMID: 30403574]
[19]
Jukema JW, Zijlstra LE, Bhatt DL, et al. ODYSSEY OUTCOMES Investigators Effect of Alirocumab on Stroke in ODYSSEY OUTCOMES. Circulation 2019; 140(25): 2054-62.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.119.043826] [PMID: 31707788]
[20]
Oesterle A, Laufs U, Liao JK. Pleiotropic Effects of Statins on the Cardiovascular System. Circ Res 2017; 120(1): 229-43.
[http://dx.doi.org/10.1161/CIRCRESAHA.116.308537] [PMID: 28057795]
[21]
Pesaro AE, Serrano CV Jr, Fernandes JL, et al. Pleiotropic effects of ezetimibe/simvastatin vs. high dose simvastatin. Int J Cardiol 2012; 158(3): 400-4.
[http://dx.doi.org/10.1016/j.ijcard.2011.01.062] [PMID: 21334753]
[22]
Sun L, Clarke R, Bennett D, et al. China Kadoorie Biobank Collaborative Group International Steering Committee; International Co-ordinating Centre, Oxford; National Co-ordinating Centre, Beijing; Regional Co-ordinating Centres. Causal associations of blood lipids with risk of ischemic stroke and intracerebral hemorrhage in Chinese adults. Nat Med 2019; 25(4): 569-74.
[http://dx.doi.org/10.1038/s41591-019-0366-x] [PMID: 30858617]
[23]
Judge C, Ruttledge S, Costello M, et al. Lipid Lowering Therapy, Low-Density Lipoprotein Level and Risk of Intracerebral Hemorrhage - A Meta-Analysis. J Stroke Cerebrovasc Dis 2019; 28(6): 1703-9.
[http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2019.02.018] [PMID: 30878368]
[24]
Brooks DC, Schindler JL. Management of Hyperlipidemia After Stroke. Curr Treat Options Cardiovasc Med 2019; 21(12): 93.
[http://dx.doi.org/10.1007/s11936-019-0774-8] [PMID: 31840196]
[25]
Faselis C, Imprialos K, Grassos H, Pittaras A, Kallistratos M, Manolis A. Is very low LDL-C harmful? Curr Pharm Des 2018; 24(31): 3658-64.
[http://dx.doi.org/10.2174/1381612824666181008110643] [PMID: 30295187]
[26]
Milionis H, Barkas F, Ntaios G, et al. Proprotein convertase subtilisin kexin 9 (PCSK9) inhibitors to treat hypercholesterolemia: Effect on stroke risk. Eur J Intern Med 2016; 34: 54-7.
[http://dx.doi.org/10.1016/j.ejim.2016.06.023] [PMID: 27363304]
[27]
Stein EA, Raal FJ. Targeting LDL: is lower better and is it safe? Best Pract Res Clin Endocrinol Metab 2014; 28(3): 309-24.
[http://dx.doi.org/10.1016/j.beem.2013.10.010] [PMID: 24840261]
[28]
Amarenco P, Kim JS, Labreuche J, et al. Treat Stroke to Target Investigators Benefit of Targeting a LDL (Low-Density Lipoprotein) Cholesterol <70 mg/dL During 5 Years After Ischemic Stroke. Stroke 2020; 51(4): 1231-9.
[http://dx.doi.org/10.1161/STROKEAHA.119.028718] [PMID: 32078484]
[29]
Amarenco P, Kim JS, Labreuche J, et al. Treat Stroke to Target Investigators A Comparison of Two LDL Cholesterol Targets after Ischemic Stroke. N Engl J Med 2020; 382(1): 9.
[http://dx.doi.org/10.1056/NEJMoa1910355] [PMID: 31738483]
[30]
Eisen A, Cannon CP, Blazing MA, et al. IMPROVE-IT (IMProved Reduction of Outcomes: Vytorin Efficacy International Trial) Investigators. The benefit of adding ezetimibe to statin therapy in patients with prior coronary artery bypass graft surgery and acute coronary syndrome in the IMPROVE-IT trial. Eur Heart J 2016; 37(48): 3576-84.
[http://dx.doi.org/10.1093/eurheartj/ehw377] [PMID: 27569841]
[31]
Nikolsky E, McLaurin BT, Cox DA, et al. Outcomes of patients with prior coronary artery bypass grafting and acute coronary syndromes: analysis from the ACUITY (Acute Catheterization and Urgent Intervention Triage Strategy) trial. JACC Cardiovasc Interv 2012; 5(9): 919-26.
[http://dx.doi.org/10.1016/j.jcin.2012.06.009] [PMID: 22995879]
[32]
Labinaz M, Kilaru R, Pieper K, et al. Outcomes of patients with acute coronary syndromes and prior coronary artery bypass grafting: results from the platelet glycoprotein IIb/IIIa in unstable angina: receptor suppression using integrilin therapy (PURSUIT) trial. Circulation 2002; 105(3): 322-7.
[http://dx.doi.org/10.1161/hc0302.102578] [PMID: 11804987]
[33]
Fanaroff AC, Roe MT, Clare RM, et al. Competing Risks of Cardiovascular Versus Noncardiovascular Death During Long-Term Follow-Up After Acute Coronary Syndromes. J Am Heart Assoc 2017; 6(9): e005840.
[http://dx.doi.org/10.1161/JAHA.117.005840] [PMID: 28923989]
[34]
Sharma A, Sun JL, Lokhnygina Y, et al. Patient Phenotypes, Cardiovascular Risk, and Ezetimibe Treatment in Patients After Acute Coronary Syndromes (from IMPROVE-IT). Am J Cardiol 2019; 123(8): 1193-201.
[http://dx.doi.org/10.1016/j.amjcard.2019.01.034] [PMID: 30739657]
[35]
Kontos MC, Wang TY, Chen AY, et al. The effect of high-risk ST elevation myocardial infarction transfer patients on risk-adjusted in-hospital mortality: A report from the American Heart Association Mission: Lifeline program. Am Heart J 2016; 180: 74-81.
[http://dx.doi.org/10.1016/j.ahj.2016.07.010] [PMID: 27659885]
[36]
McManus DD, Gore J, Yarzebski J, Spencer F, Lessard D, Goldberg RJ. Recent trends in the incidence, treatment, and outcomes of patients with STEMI and NSTEMI. Am J Med 2011; 124(1): 40-7.
[http://dx.doi.org/10.1016/j.amjmed.2010.07.023] [PMID: 21187184]
[37]
Ambrosy AP, Cerbin LP, Fudim M, et al. Natural History of Patients Postacute Coronary Syndrome Based on Heart Failure Status. Am J Cardiol 2018; 122(9): 1451-8.
[http://dx.doi.org/10.1016/j.amjcard.2018.07.034] [PMID: 30180960]
[38]
Bonaca MP, Gutierrez JA, Cannon C, et al. Polyvascular disease, type 2 diabetes, and long-term vascular risk: a secondary analysis of the IMPROVE-IT trial. Lancet Diabetes Endocrinol 2018; 6(12): 934-43.
[http://dx.doi.org/10.1016/S2213-8587(18)30290-0] [PMID: 30396865]
[39]
Qamar A, Giugliano RP, Bohula EA, et al. Biomarkers and Clinical Cardiovascular Outcomes With Ezetimibe in the IMPROVE-IT Trial. J Am Coll Cardiol 2019; 74(8): 1057-68.
[http://dx.doi.org/10.1016/j.jacc.2019.06.038] [PMID: 31439215]
[40]
Ford I, Shah AS, Zhang R, et al. High-sensitivity cardiac troponin, statin therapy, and risk of coronary heart disease. J Am Coll Cardiol 2016; 68(25): 2719-28.
[http://dx.doi.org/10.1016/j.jacc.2016.10.020] [PMID: 28007133]
[41]
White HD, Tonkin A, Simes J, et al. LIPID Study Investigators Association of contemporary sensitive troponin I levels at baseline and change at 1 year with long-term coronary events following myocardial infarction or unstable angina: results from the LIPID Study (Long-Term Intervention With Pravastatin in Ischaemic Disease). J Am Coll Cardiol 2014; 63(4): 345-54.
[http://dx.doi.org/10.1016/j.jacc.2013.08.1643] [PMID: 24140630]
[42]
Giugliano RP, Keech A, Murphy SA, et al. Clinical Efficacy and Safety of Evolocumab in High-Risk Patients Receiving a Statin: Secondary Analysis of Patients With Low LDL Cholesterol Levels and in Those Already Receiving a Maximal-Potency Statin in a Randomized Clinical Trial. JAMA Cardiol 2017; 2(12): 1385-91.
[http://dx.doi.org/10.1001/jamacardio.2017.3944] [PMID: 29117276]
[43]
Kritchevsky SB. Dietary lipids and the low blood cholesterol-cancer association. Am J Epidemiol 1992; 135(5): 509-20.
[http://dx.doi.org/10.1093/oxfordjournals.aje.a116318] [PMID: 1570817]
[44]
Neaton JD, Blackburn H, Jacobs D, et al. Multiple Risk Factor Intervention Trial Research Group Serum cholesterol level and mortality findings for men screened in the Multiple Risk Factor Intervention Trial. Arch Intern Med 1992; 152(7): 1490-500.
[http://dx.doi.org/10.1001/archinte.1992.00400190110021] [PMID: 1627030]
[45]
Tirschwell DL, Smith NL, Heckbert SR, Lemaitre RN, Longstreth WT Jr, Psaty BM. Association of cholesterol with stroke risk varies in stroke subtypes and patient subgroups. Neurology 2004; 63(10): 1868-75.
[http://dx.doi.org/10.1212/01.WNL.0000144282.42222.DA] [PMID: 15557504]
[46]
Berry PH, MacDonald JS, Alberts AW, et al. Brain and optic system pathology in hypocholesterolemic dogs treated with a competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase. Am J Pathol 1988; 132(3): 427-43.
[PMID: 3414776]
[47]
Giugliano RP, Wiviott SD, Blazing MA, et al. Long-term Safety and Efficacy of Achieving Very Low Levels of Low-Density Lipoprotein Cholesterol: A Prespecified Analysis of the IMPROVE-IT Trial. JAMA Cardiol 2017; 2(5): 547-55.
[http://dx.doi.org/10.1001/jamacardio.2017.0083] [PMID: 28291866]
[48]
Arnold SV, Spertus JA, Masoudi FA, et al. Beyond medication prescription as performance measures: optimal secondary prevention medication dosing after acute myocardial infarction. J Am Coll Cardiol 2013; 62(19): 1791-801.
[http://dx.doi.org/10.1016/j.jacc.2013.04.102] [PMID: 23973701]
[49]
Lauffenburger JC, Robinson JG, Oramasionwu C, Fang G. Racial/Ethnic and gender gaps in the use of and adherence to evidence-based preventive therapies among elderly Medicare Part D beneficiaries after acute myocardial infarction. Circulation 2014; 129(7): 754-63.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.113.002658] [PMID: 24326988]
[50]
Ho PM, Spertus JA, Masoudi FA, et al. Impact of medication therapy discontinuation on mortality after myocardial infarction. Arch Intern Med 2006; 166(17): 1842-7.
[http://dx.doi.org/10.1001/archinte.166.17.1842] [PMID: 17000940]
[51]
Halvorsen S, Jortveit J, Hasvold P, Thuresson M, Øie E. Initiation of and long-term adherence to secondary preventive drugs after acute myocardial infarction. BMC Cardiovasc Disord 2016; 16: 115.
[http://dx.doi.org/10.1186/s12872-016-0283-6] [PMID: 27246583]
[52]
Mathews R, Wang TY, Honeycutt E, et al. TRANSLATE-ACS Study Investigators Persistence with secondary prevention medications after acute myocardial infarction: Insights from the TRANSLATE-ACS study. Am Heart J 2015; 170(1): 62-9.
[http://dx.doi.org/10.1016/j.ahj.2015.03.019] [PMID: 26093865]
[53]
Vinogradova Y, Coupland C, Brindle P, Hippisley-Cox J. Discontinuation and restarting in patients on statin treatment: prospective open cohort study using a primary care database. BMJ 2016; 353: i3305.
[http://dx.doi.org/10.1136/bmj.i3305] [PMID: 27353261]
[54]
De Geest S, Zullig LL, Dunbar-Jacob J, et al. ESPACOMP Medication Adherence Reporting Guideline (EMERGE). Ann Intern Med 2018; 169(1): 30-5.
[http://dx.doi.org/10.7326/M18-0543] [PMID: 29946690]
[55]
Ellis JJ, Erickson SR, Stevenson JG, Bernstein SJ, Stiles RA, Fendrick AM. Suboptimal statin adherence and discontinuation in primary and secondary prevention populations. J Gen Intern Med 2004; 19(6): 638-45.
[http://dx.doi.org/10.1111/j.1525-1497.2004.30516.x] [PMID: 15209602]
[56]
Rosenbaum D, Dallongeville J, Sabouret P, Bruckert E. Discontinuation of statin therapy due to muscular side effects: a survey in real life. Nutr Metab Cardiovasc Dis 2013; 23(9): 871-5.
[http://dx.doi.org/10.1016/j.numecd.2012.04.012] [PMID: 22748604]
[57]
Wei MY, Ito MK, Cohen JD, Brinton EA, Jacobson TA. Predictors of statin adherence, switching, and discontinuation in the USAGE survey: understanding the use of statins in America and gaps in patient education. J Clin Lipidol 2013; 7(5): 472-83.
[http://dx.doi.org/10.1016/j.jacl.2013.03.001] [PMID: 24079289]
[58]
Stroes ES, Thompson PD, Corsini A, et al. European Atherosclerosis Society Consensus Panel. Statin-associated muscle symptoms: impact on statin therapy-European Atherosclerosis Society Consensus Panel Statement on Assessment, Aetiology and Management. Eur Heart J 2015; 36(17): 1012-22.
[http://dx.doi.org/10.1093/eurheartj/ehv043] [PMID: 25694464]
[59]
Banach M, Rizzo M, Toth PP, et al. Statin intolerance - an attempt at a unified definition. Position paper from an International Lipid Expert Panel. Arch Med Sci 2015; 11(1): 1-23.
[http://dx.doi.org/10.5114/aoms.2015.49807] [PMID: 25861286]
[60]
Navar AM, Roe MT, White JA, et al. Medication Discontinuation in the IMPROVE-IT Trial. Circ Cardiovasc Qual Outcomes 2019; 12(1)e005041
[http://dx.doi.org/10.1161/CIRCOUTCOMES.118.005041] [PMID: 30630361]
[61]
Andrade SE, Walker AM, Gottlieb LK, et al. Discontinuation of antihyperlipidemic drugs--do rates reported in clinical trials reflect rates in primary care settings? N Engl J Med 1995; 332(17): 1125-31.
[http://dx.doi.org/10.1056/NEJM199504273321703] [PMID: 7700285]
[62]
Nanna MG, Navar AM, Giugliano RP, et al. Muscle Complaints or Events in Patients Randomized to Simvastatin or Ezetimibe/Simvastatin. J Am Coll Cardiol 2020; 75(7): 835-7.
[http://dx.doi.org/10.1016/j.jacc.2019.12.022] [PMID: 32081289]
[63]
Banach M, Mikhailidis DP. Statin Intolerance: Some Practical Hints. Cardiol Clin 2018; 36(2): 225-31.
[http://dx.doi.org/10.1016/j.ccl.2017.12.004] [PMID: 29609752]
[64]
Almalki ZS, Guo JJ, Alahmari A, Alotaibi N, Thaibah H. Cost-Effectiveness of Simvastatin Plus Ezetimibe for Cardiovascular Prevention in Patients With a History of Acute Coronary Syndrome: Analysis of Results of the IMPROVE-IT Trial. Heart Lung Circ 2018; 27(6): 656-65.
[http://dx.doi.org/10.1016/j.hlc.2017.05.139] [PMID: 28716519]
[65]
Agency for Healthcare Research and Quality HCUPnet: A tool for identifying, tracking, and analyzing national hospital statistics http://hcupnet.ahrq.gov/
[66]
Ara R, Pandor A, Tumur I, et al. Estimating the health benefits and costs associated with ezetimibe coadministered with statin therapy compared with higher dose statin monotherapy in patients with established cardiovascular disease: results of a Markov model for UK costs using data registries. Clin Ther 2008; 30(8): 1508-23.
[http://dx.doi.org/10.1016/j.clinthera.2008.08.002] [PMID: 18803993]
[67]
van Nooten F, Davies GM, Jukema JW, Liem AH, Yap E, Hu XH. Economic evaluation of ezetimibe combined with simvastatin for the treatment of primary hypercholesterolaemia. Neth Heart J 2011; 19(2): 61-7.
[http://dx.doi.org/10.1007/s12471-010-0061-5] [PMID: 22020943]
[68]
Reckless J, Davies G, Tunceli K, Hu XH, Brudi P. Projected cost-effectiveness of ezetimibe/simvastatin compared with doubling the statin dose in the United Kingdom: findings from the INFORCE study. Value Health 2010; 13(6): 726-34.
[http://dx.doi.org/10.1111/j.1524-4733.2010.00742.x] [PMID: 20561328]
[69]
Pokharel Y, Chinnakondepalli K, Vilain K, et al. Impact of Ezetimibe on the Rate of Cardiovascular-Related Hospitalizations and Associated Costs Among Patients With a Recent Acute Coronary Syndrome: Results From the IMPROVE-IT Trial (Improved Reduction of Outcomes: Vytorin Efficacy International Trial). Circ Cardiovasc Qual Outcomes 2017; 10(5): e003201.
[http://dx.doi.org/10.1161/CIRCOUTCOMES.116.003201] [PMID: 28506979]
[70]
Mahoney EM, Wang K, Keo HH, et al. Reduction of Atherothrombosis for Continued Health (REACH) Registry Investigators Vascular hospitalization rates and costs in patients with peripheral artery disease in the United States. Circ Cardiovasc Qual Outcomes 2010; 3(6): 642-51.
[http://dx.doi.org/10.1161/CIRCOUTCOMES.109.930735] [PMID: 20940249]
[71]
Mahoney EM, Wang K, Cohen DJ, et al. REACH Registry Investigators One-year costs in patients with a history of or at risk for atherothrombosis in the United States. Circ Cardiovasc Qual Outcomes 2008; 1(1): 38-45.
[http://dx.doi.org/10.1161/CIRCOUTCOMES.108.775247] [PMID: 20031786]
[72]
Arbel R, Hammerman A, Azuri J. Usefulness of Ezetimibe Versus Evolocumab as Add-On Therapy for Secondary Prevention of Cardiovascular Events in Patients With Type 2 Diabetes Mellitus. Am J Cardiol 2019; 123(8): 1273-6.
[http://dx.doi.org/10.1016/j.amjcard.2019.01.021] [PMID: 30711247]
[74]
McConnachie A, Walker A, Robertson M, et al. Long-term impact on healthcare resource utilization of statin treatment, and its cost effectiveness in the primary prevention of cardiovascular disease: a record linkage study. Eur Heart J 2014; 35(5): 290-8.
[http://dx.doi.org/10.1093/eurheartj/eht232] [PMID: 23839541]
[75]
Pandya A, Sy S, Cho S, Weinstein MC, Gaziano TA. Cost-effectiveness of 10-Year Risk Thresholds for Initiation of Statin Therapy for Primary Prevention of Cardiovascular Disease. JAMA 2015; 314(2): 142-50.
[http://dx.doi.org/10.1001/jama.2015.6822] [PMID: 26172894]
[76]
Ward S, Lloyd Jones M, Pandor A, et al. A systematic review and economic evaluation of statins for the prevention of coronary events. Health Technol Assess 2007; 11(14): 1-160.
[http://dx.doi.org/10.3310/hta11140] [PMID: 17408535]
[77]
Kotseva K, De Bacquer D, De Backer G, et al. On Behalf of The Euroaspire Investigators Lifestyle and risk factor management in people at high risk of cardiovascular disease. A report from the European Society of Cardiology European Action on Secondary and Primary Prevention by Intervention to Reduce Events (EUROASPIRE) IV cross-sectional survey in 14 European regions. Eur J Prev Cardiol 2016; 23(18): 2007-18.
[http://dx.doi.org/10.1177/2047487316667784] [PMID: 27638542]
[78]
Vonbank A, Agewall S, Kjeldsen KP, et al. Comprehensive efforts to increase adherence to statin therapy. Eur Heart J 2017; 38(32): 2473-9.
[http://dx.doi.org/10.1093/eurheartj/ehw628] [PMID: 28077470]
[79]
Davies GM, Vyas A, Baxter CA. Economic evaluation of ezetimibe treatment in combination with statin therapy in the United States. J Med Econ 2017; 20(7): 723-31.
[http://dx.doi.org/10.1080/13696998.2017.1320559] [PMID: 28426345]
[80]
Virani SS, Akeroyd JM, Nambi V, et al. Implications for Ezetimibe Therapy Use Based on IMPROVE-IT Criteria. Am J Med 2015; 128(11): 1253-6.
[http://dx.doi.org/10.1016/j.amjmed.2015.05.027] [PMID: 26071828]
[81]
Maddox TM, Tang F, Downs JR, et al. Applicability of the IMPROVE-IT Trial to Current Patients With Acute Coronary Syndrome: An NCDR Research to Practice Project. JAMA Intern Med 2017; 177(6): 887-9.
[http://dx.doi.org/10.1001/jamainternmed.2017.0754] [PMID: 28437531]
[82]
Piepoli MF, Hoes AW, Agewall S, et al. ESC Scientific Document Group 2016 European Guidelines on cardiovascular disease prevention in clinical practice: The Sixth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by representatives of 10 societies and by invited experts)Developed with the special contribution of the European Association for Cardiovascular Prevention & Rehabilitation (EACPR). Eur Heart J 2016; 37(29): 2315-81.
[http://dx.doi.org/10.1093/eurheartj/ehw106] [PMID: 27222591]
[83]
Gencer B, Carballo D, Nanchen D, et al. Intensified lipid lowering using ezetimibe after publication of the IMPROVE-IT trial: A contemporary analysis from the SPUM-ACS cohort. Int J Cardiol 2020; 303: 8-13.
[http://dx.doi.org/10.1016/j.ijcard.2019.12.011] [PMID: 31859113]
[84]
Robinson JG, Huijgen R, Ray K, Persons J, Kastelein JJ, Pencina MJ. Determining When to Add Nonstatin Therapy: A Quantitative Approach. J Am Coll Cardiol 2016; 68(22): 2412-21.
[http://dx.doi.org/10.1016/j.jacc.2016.09.928] [PMID: 27908345]
[86]
National Institute for Health and Care Excellence (NICE) Ezetimibe for Treating Primary Heterozygous-Familial and Non-Familial Hypercholesterolaemia 2016. Available at : https://www.nice.org.uk/guidance/TA385/chapter/1-Recommendations
[87]
Lloyd-Jones DM, Morris PB, Ballantyne CM, et al. Writing Committee 2016 ACC Expert Consensus Decision Pathway on the Role of Non-Statin Therapies for LDL-Cholesterol Lowering in the Management of Atherosclerotic Cardiovascular Disease Risk: A Report of the American College of Cardiology Task Force on Clinical Expert Consensus Documents. J Am Coll Cardiol 2016; 68(1): 92-125.
[http://dx.doi.org/10.1016/j.jacc.2016.03.519] [PMID: 27046161]
[88]
Grundy SM, Stone NJ, Bailey AL, et al. 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. Circulation 2019; 139(25): e1082-143.
[PMID: 30586774]
[89]
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): 111-88.
[http://dx.doi.org/10.1093/eurheartj/ehz455] [PMID: 31504418]
[90]
Baigent C, Keech A, Kearney PM, et al. Cholesterol Treatment Trialists’ (CTT) Collaborators Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90,056 participants in 14 randomised trials of statins. Lancet 2005; 366(9493): 1267-78.
[http://dx.doi.org/10.1016/S0140-6736(05)67394-1] [PMID: 16214597]
[91]
Fulcher J, O’Connell R, Voysey M, et al. Cholesterol Treatment Trialists’ (CTT) Collaboration Efficacy and safety of LDL-lowering therapy among men and women: meta-analysis of individual data from 174,000 participants in 27 randomised trials. Lancet 2015; 385(9976): 1397-405.
[http://dx.doi.org/10.1016/S0140-6736(14)61368-4] [PMID: 25579834]
[92]
Mills EJ, Wu P, Chong G, et al. Efficacy and safety of statin treatment for cardiovascular disease: a network meta-analysis of 170,255 patients from 76 randomized trials. QJM 2011; 104(2): 109-24.
[http://dx.doi.org/10.1093/qjmed/hcq165] [PMID: 20934984]
[93]
Kearney PM, Blackwell L, Collins R, et al. Cholesterol Treatment Trialists’ (CTT) Collaborators Efficacy of cholesterol-lowering therapy in 18,686 people with diabetes in 14 randomised trials of statins: a meta-analysis. Lancet 2008; 371(9607): 117-25.
[http://dx.doi.org/10.1016/S0140-6736(08)60104-X] [PMID: 18191683]
[94]
Agouridis AP, Mikhailidis DP. Should we consider ezetimibe to reach even lower LDL-C targets? Curr Med Res Opin 2015; 31(3): 459-60.
[http://dx.doi.org/10.1185/03007995.2015.1005204] [PMID: 25565356]
[95]
Upadhyay A, Earley A, Lamont JL, Haynes S, Wanner C, Balk EM. Lipid-lowering therapy in persons with chronic kidney disease: a systematic review and meta-analysis. Ann Intern Med 2012; 157(4): 251-62.
[http://dx.doi.org/10.7326/0003-4819-157-4-201208210-00005] [PMID: 22910936]
[96]
Rizzo M, Barylski M, Rizvi AA, Montalto G, Mikhailidis DP, Banach M. Combined dyslipidemia: should the focus be LDL cholesterol or atherogenic dyslipidemia? Curr Pharm Des 2013; 19(21): 3858-68.
[http://dx.doi.org/10.2174/13816128113199990324] [PMID: 23286436]
[97]
Kastelein JJ, Akdim F, Stroes ES, et al. ENHANCE Investigators Simvastatin with or without ezetimibe in familial hypercholesterolemia. N Engl J Med 2008; 358(14): 1431-43.
[http://dx.doi.org/10.1056/NEJMoa0800742] [PMID: 18376000]
[98]
Paraskevas KI, Veith FJ, Mikhailidis DP. Carotid intima-media thickness and ezetimibe: the end of a misunderstanding? Curr Vasc Pharmacol 2011; 9(4): 381-4.
[http://dx.doi.org/10.2174/157016111796197198] [PMID: 21574949]
[99]
Paraskevas KI, Mikhailidis DP. More on carotid atherosclerosis and ezetimibe. Int Angiol 2017; 36(6): 580-1.
[PMID: 28854780]
[100]
Wang J, Ai XB, Wang F, Zou YW, Li L, Yi XL. Efficacy of ezetimibe combined with atorvastatin in the treatment of carotid artery plaque in patients with type 2 diabetes mellitus complicated with coronary heart disease. Int Angiol 2017; 36(5): 467-73.
[PMID: 28641407]
[101]
Luo P, Wang L, Zhu H, Du S, Wang G, Ding S. Impact of Atorvastatin Combined with Ezetimibe for the Treatment of Carotid Atherosclerosis in Patients with Coronary Heart Disease. Acta Cardiol Sin 2016; 32(5): 578-85.
[PMID: 27713607]
[102]
Avellone G, Di Garbo V, Guarnotta V, et al. Efficacy and safety of long-term ezetimibe/simvastatin treatment in patients with familial hypercholesterolemia. Int Angiol 2010; 29(6): 514-24.
[PMID: 21173733]
[103]
Gudzune KA, Monroe AK, Sharma R, Ranasinghe PD, Chelladurai Y, Robinson KA. Effectiveness of combination therapy with statin and another lipid-modifying agent compared with intensified statin monotherapy: a systematic review. Ann Intern Med 2014; 160(7): 468-76.
[http://dx.doi.org/10.7326/M13-2526] [PMID: 24514899]
[104]
Sharma M, Ansari MT, Abou-Setta AM, et al. Systematic review: comparative effectiveness and harms of combination therapy and monotherapy for dyslipidemia. Ann Intern Med 2009; 151(9): 622-30.
[http://dx.doi.org/10.7326/0003-4819-151-9-200911030-00144] [PMID: 19884623]
[105]
Savarese G, De Ferrari GM, Rosano GM, Perrone-Filardi P. Safety and efficacy of ezetimibe: A meta-analysis. Int J Cardiol 2015; 201: 247-52.
[http://dx.doi.org/10.1016/j.ijcard.2015.08.103] [PMID: 26301648]
[106]
Thomopoulos C, Skalis G, Michalopoulou H, Tsioufis C, Makris T. Effect of Low-Density Lipoprotein Cholesterol Lowering by Ezetimibe/Simvastatin on Outcome Incidence: Overview, Meta-Analyses, and Meta-Regression Analyses of Randomized Trials. Clin Cardiol 2015; 38(12): 763-9.
[http://dx.doi.org/10.1002/clc.22441] [PMID: 26282344]
[107]
Wong ND, Young D, Zhao Y, et al. Prevalence of the American College of Cardiology/American Heart Association statin eligibility groups, statin use, and low-density lipoprotein cholesterol control in US adults using the National Health and Nutrition Examination Survey 2011-2012. J Clin Lipidol 2016; 10(5): 1109-18.
[http://dx.doi.org/10.1016/j.jacl.2016.06.011] [PMID: 27678427]
[108]
Shrank WH, Barlow JF, Brennan TA. New Therapies in the Treatment of High Cholesterol: An Argument to Return to Goal-Based Lipid Guidelines. JAMA 2015; 314(14): 1443-4.
[http://dx.doi.org/10.1001/jama.2015.10017] [PMID: 26258765]
[109]
Heart Protection Study Collaborative Group MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial. Lancet 2002; 360(9326): 7-22.
[http://dx.doi.org/10.1016/S0140-6736(02)09327-3] [PMID: 12114036]
[110]
Bohula EA, Giugliano RP, Cannon CP, et al. Achievement of dual low-density lipoprotein cholesterol and high-sensitivity C-reactive protein targets more frequent with the addition of ezetimibe to simvastatin and associated with better outcomes in IMPROVE-IT. Circulation 2015; 132(13): 1224-33.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.115.018381] [PMID: 26330412]
[111]
Nissen SE, Tuzcu EM, Schoenhagen P, et al. REVERSAL Investigators Effect of intensive compared with moderate lipid-lowering therapy on progression of coronary atherosclerosis: a randomized controlled trial. JAMA 2004; 291(9): 1071-80.
[http://dx.doi.org/10.1001/jama.291.9.1071] [PMID: 14996776]
[112]
Habara M, Nasu K, Terashima M, et al. Impact on optical coherence tomographic coronary findings of fluvastatin alone versus fluvastatin + ezetimibe. Am J Cardiol 2014; 113(4): 580-7.
[http://dx.doi.org/10.1016/j.amjcard.2013.10.038] [PMID: 24388622]
[113]
Rosenblit PD. Lowering Targeted Atherogenic Lipoprotein Cholesterol Goals for Patients at “Extreme” ASCVD Risk. Curr Diab Rep 2019; 19(12): 146.
[http://dx.doi.org/10.1007/s11892-019-1246-y] [PMID: 31754844]
[114]
Serban MC, Banach M, Mikhailidis DP. Clinical implications of the IMPROVE-IT trial in the light of current and future lipid-lowering treatment options. Expert Opin Pharmacother 2016; 17(3): 369-80.
[http://dx.doi.org/10.1517/14656566.2016.1118055] [PMID: 26559810]
[115]
Mortensen MB, Blaha MJ, Nordestgaard BG. Eligibility and Preventive Potential for New Evidence-Based Cardiovascular Drugs in Secondary Prevention. JAMA Cardiol 2020; 5(2): 209-15.
[http://dx.doi.org/10.1001/jamacardio.2019.4759] [PMID: 31895459]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy