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Efficacy of Statin/Ezetimibe for Secondary Prevention of Atherosclerotic Cardiovascular Disease in Asian Populations: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

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Abstract

Background

Several clinical trials have investigated the effect of statin/ezetimibe combination therapy on secondary prevention of atherosclerotic cardiovascular disease (ASCVD) in the Asian population.

Objective

This study aimed to summarize study results regarding the effect of statin/ezetimibe combination therapy on lipid parameters and highly sensitive C-reactive protein (HsCRP) biomarkers in ASCVD patients from Asian countries.

Methods

We searched the PubMed/MEDLINE, Web of Science, Scopus, and Google Scholar databases for relevant papers published from 2008 to June 2020. We included randomized controlled trials (RCTs) that (1) were conducted in ASCVD patients in Asian countries; (2) examined the effects of statin/ezetimibe combination therapies compared with a control group; and (3) reported sufficient data on lipid parameters and HsCRP biomarkers. The results were reported as weighted mean differences (WMDs) with 95% confidence intervals (CI) using random-effects models. Funnel plots and Egger’s regression test were used to assess publication bias.

Results

Twenty-four RCTs were reviewed and 20 were included in the meta-analysis. A total of 4344 participants were included (n = 2197 in the intervention group and n = 2147 in the control group), and the intervention durations ranged from 6 weeks to 3.6 years. Ezetimibe coadministered with statin therapy, compared with control treatment, significantly reduced low-density lipoprotein cholesterol (LDL-C; n = 20 studies) [WMD  − 0.39 mmol/L, 95% CI − 0.73 to − 0.05; p < 0.001], triglycerides (TG; n = 18 studies) [WMD − 0.23 mmol/L, 95% CI − 0.33 to − 0.13; p < 0.001], and total cholesterol (TC; n = 17 studies) [WMD − 0.31 mmol/L, 95% CI − 0.45 to − 0.17; p < 0.001). Although the effect of statin/ezetimibe combinations on high-density lipoprotein cholesterol (HDL-C; n = 17 studies) [WMD 0.02 mmol/L, 95% CI − 0.05 to 0.09; p < 0.001) was very minimal and no effect was observed on HsCRP levels (n = 11 studies).

Conclusions

Our study found that statin/ezetimibe combinations reduced LDL-C, TC, and TG levels but had minimal effects on HDL-C and no effect HsCRP biomarkers in ASCVD patients. The statin/ezetimibe therapy enabled a more effective reduction in LDL-C levels; however, the duration of the treatment was suboptimal.

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References

  1. Gidding SS, Allen NB. Cholesterol and atherosclerotic cardiovascular disease: a lifelong problem. J Am Heart Assoc. 2019;8:e012924. https://doi.org/10.1161/JAHA.119.012924.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Boekholdt SM, Arsenault BJ, Mora S, Pedersen TR, LaRosa JC, Nestel PJ, et al. Association of LDL cholesterol, non-HDL cholesterol, and apolipoprotein B levels with risk of cardiovascular events among patients treated with statins: a meta-analysis. JAMA. 2012;307:1302–9. https://doi.org/10.1001/jama.2012.366.

    Article  CAS  PubMed  Google Scholar 

  3. Piepoli MF, Hoes AW, Agewall S, Albus C, Brotons C, Catapano AL, et al. 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;37:2315–81. https://doi.org/10.1093/eurheartj/ehw106.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Kinoshita M, Yokote K, Arai H, Iida M, Ishigaki Y, Ishibashi S, et al. Japan Atherosclerosis Society (JAS) guidelines for prevention of atherosclerotic cardiovascular diseases 2017. J Atheroscler Thromb. 2018;25:846–98484. https://doi.org/10.5551/jat.GL2017.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Lloyd-Jones DM, Morris PB, Ballantyne CM, Birtcher KK, Daly DD, DePalma SM, et al. 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;68:92–125. https://doi.org/10.1016/j.jacc.2016.03.519.

    Article  PubMed  Google Scholar 

  6. Grundy SM, Stone NJ, Bailey AL, Beam C, Birtcher KK, Blumenthal RS, 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. J Am Coll Cardiol. 2019;73:e285–350. https://doi.org/10.1016/j.jacc.2018.11.003.

    Article  PubMed  Google Scholar 

  7. Arnett DK, Blumenthal RS, Albert MA, Michos ED, Buroker AB, Miedema MD, et al. 2019 ACC/AHA guideline on the primary prevention of cardiovascular disease. J Am Coll Cardiol. 2019;73:260–32929. https://doi.org/10.1161/CIR.0000000000000678.

    Article  Google Scholar 

  8. Authors/Task Force Members; ESC Committee for Practice Guidelines (CPG); ESC National Cardiac Societies. ESC/EAS Guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk. Atherosclerosis. 2019;2019(290):140–205. https://doi.org/10.1016/j.atherosclerosis.2019.08.014.

    Article  CAS  Google Scholar 

  9. Jeu L, Cheng JW. Pharmacology and therapeutics of ezetimibe (SCH 58235), a cholesterol-absorption inhibitor. Clin Ther. 2003;25(9):2352–87. https://doi.org/10.1016/s0149-2918(03)80281-3.

    Article  CAS  PubMed  Google Scholar 

  10. Jacobson TA, Ito MK, Maki KC, Orringer CE, Bays HE, Jones PH. National lipid association recommendations for patient-centered management of dyslipidemia: part 1—full report. J Clin Lipidol. 2015;9:129–69. https://doi.org/10.1016/j.jacl.2015.02.003.

    Article  PubMed  Google Scholar 

  11. Morrone D, Weintraub WS, Toth PP, Hanson ME, Lowe RS, Lin J, et al. Lipid-altering efficacy of ezetimibe plus statin and statin monotherapy and identification of factors associated with treatment response: a pooled analysis of over 21,000 subjects from 27 clinical trials. Atherosclerosis. 2012;223:251–61. https://doi.org/10.1016/j.atherosclerosis.2012.02.016.

    Article  CAS  PubMed  Google Scholar 

  12. Shaya FT, Sing K, Milam R, Husain F, del Aguila MA, Patel MY. Lipid-lowering efficacy of ezetimibe in patients with atherosclerotic cardiovascular disease: a systematic review and meta-analyses. Am J Cardiovasc Drugs. 2020;20:239–48. https://doi.org/10.1007/s40256-019-00379-9.

    Article  PubMed  Google Scholar 

  13. Koskinas KC, Siontis GC, Piccolo R, Mavridis D, Räber L, Mach F, et al. Effect of statins and non-statin LDL-lowering medications on cardiovascular outcomes in secondary prevention: a meta-analysis of randomized trials. Eur Heart J. 2017;39(14):1172–80. https://doi.org/10.1093/eurheartj/ehx566.

    Article  CAS  Google Scholar 

  14. Zhan S, Tang M, Liu F, Xia P, Shu M, Wu X. Ezetimibe for the prevention of cardiovascular disease and all‐cause mortality events. Cochrane Database Syst Rev. 2018;(11):CD012502. https://doi.org/10.1002/14651858.CD012502.pub2.

  15. Cannon CP, Blazing MA, Giugliano RP, McCagg A, White JA, Theroux P, et al. Ezetimibe added to statin therapy after acute coronary syndromes. N Engl J Med. 2015;372:2387–97. https://doi.org/10.1056/NEJMoa1410489.

    Article  CAS  PubMed  Google Scholar 

  16. Moher D, Shamseer L, Clarke M, Ghersi D, Liberati A, Petticrew M, et al. Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015 statement. Syst Rev. 2015;4:1. https://doi.org/10.1186/2046-4053-4-1.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Higgins JP, Altman DG, Gøtzsche PC, Jüni P, Moher D, Oxman AD, et al. The Cochrane collaboration’s tool for assessing risk of bias in randomised trials. BMJ. 2011;343:d5928. https://doi.org/10.1136/bmj.d5928.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Oh M, Kim H, Shin EW, Sung C, Kim DH, Moon DH, Lee CW. Effects of ezetimibe/simvastatin 10/10 mg versus rosuvastatin 10 mg on carotid atherosclerotic plaque inflammation. BMC Cardiovasc Disorder. 2019;19(1):201. https://doi.org/10.1186/s12872-019-1184-2.

    Article  CAS  Google Scholar 

  19. Wu NQ, Guo YL, Zhu CG, Gao Y, Zhao X, Sun D, et al. Comparison of statin plus ezetimibe with double-dose statin on lipid profiles and inflammation markers. Lipid Health Dis. 2018;17(1):265. https://doi.org/10.1186/s12944-018-0909-z.

    Article  CAS  Google Scholar 

  20. Hibi K, Sonoda S, Kawasaki M, Otsuji Y, Murohara T, Ishii H, et al. Effects of ezetimibe-statin combination therapy on coronary atherosclerosis in acute coronary syndrome. Circ J. 2018;82:757–66. https://doi.org/10.1253/circj.CJ-17-0598.

    Article  CAS  PubMed  Google Scholar 

  21. Takase S, Matoba T, Nakashiro S, Mukai Y, Inoue S, Oi K, et al. Ezetimibe in combination with statins ameliorates endothelial dysfunction in coronary arteries after stenting: the CuVIC trial (effect of cholesterol absorption inhibitor usage on target vessel dysfunction after coronary stenting), a multicenter randomized controlled trial. Arterioscler Thromb Vasc Biol. 2017;37:350–8. https://doi.org/10.1161/ATVBAHA.116.308388.

    Article  CAS  PubMed  Google Scholar 

  22. Liu Z, Hao H, Yin C, Chu Y, Li J, Xu D. Therapeutic effects of atorvastatin and ezetimibe compared with double-dose atorvastatin in very elderly patients with acute coronary syndrome. Oncotarget. 2017;8:41582. https://doi.org/10.18632/oncotarget.15078.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Ran D, Nie HJ, Gao YL, Deng SB, Du JL, Liu YJ, et al. A randomized, controlled comparison of different intensive lipid-lowering therapies in Chinese patients with non-ST-elevation acute coronary syndrome (NSTE-ACS): Ezetimibe and rosuvastatin versus high-dose rosuvastatin. Int J Cardiol. 2017;235:49–55. https://doi.org/10.1016/j.ijcard.2017.02.099.

    Article  PubMed  Google Scholar 

  24. Joshi S, Sharma R, Rao HK, Narang U, Gupta N. Efficacy of combination therapy of rosuvastatin and ezetimibe vs rosuvastatin monotherapy on lipid profile of patients with coronary artery disease. J Clin Diagn Res. 2017;11:28–31. https://doi.org/10.7860/JCDR/2017/30458.11004.

    Article  Google Scholar 

  25. 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;36:467–73. https://doi.org/10.23736/S0392-9590.17.03818-4.

    Article  PubMed  Google Scholar 

  26. Ueda Y, Hiro T, Hirayama A, Komatsu S, Matsuoka H, Takayama T, et al. Effect of ezetimibe on stabilization and regression of intracoronary plaque—the ZIPANGU study. Circulation J. 2017;81:1611–7. https://doi.org/10.1253/circj.CJ-17-0193.

    Article  CAS  Google Scholar 

  27. Ren Y, Zhu H, Fan Z, Gao Y, Tian N. Comparison of the effect of rosuvastatin versus rosuvastatin/ezetimibe on markers of inflammation in patients with acute myocardial infarction. Exp Ther Med. 2017;14:4942–50. https://doi.org/10.3892/etm.2017.5175.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Hagiwara N, Kawada-Watanabe E, Koyanagi R, Arashi H, Yamaguchi J, Nakao K, et al. Low-density lipoprotein cholesterol targeting with pitavastatin + ezetimibe for patients with acute coronary syndrome and dyslipidaemia: the HIJ-PROPER study, a prospective, open-label, randomized trial. Eur Heart J. 2017;38:2264–76. https://doi.org/10.1093/eurheartj/ehx162.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Yang YJ, Lee SH, Kim BS, Cho YK, Cho HJ, Im Cho K, et al. Combination therapy of rosuvastatin and ezetimibe in patients with high cardiovascular risk. Clin Ther. 2017;39:107–17. https://doi.org/10.1016/j.clinthera.2016.11.014.

    Article  CAS  PubMed  Google Scholar 

  30. Lin H, Zhang YM. The effect of ezetimibe and simvastatin combination therapy on percutaneous coronary intervention patients. Int J Cardiol. 2017;242:1–3. https://doi.org/10.1016/j.ijcard.2016.10.083.

    Article  PubMed  Google Scholar 

  31. Wang X, Zhao X, Li L, Yao H, Jiang Y, Zhang J. Effects of combination of ezetimibe and rosuvastatin on coronary artery plaque in patients with coronary heart disease. Heart Lung Circ. 2016;25:459–65. https://doi.org/10.1016/j.hlc.2015.10.012.

    Article  PubMed  Google Scholar 

  32. 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;32:578. https://doi.org/10.6515/acs20151013h.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Masuda J, Tanigawa T, Yamada T, Nishimura Y, Sasou T, Nakata T, et al. Effect of combination therapy of ezetimibe and rosuvastatin on regression of coronary atherosclerosis in patients with coronary artery disease. Int Heart J. 2015;56(3):278–85. https://doi.org/10.1536/ihj.14-311.

    Article  CAS  PubMed  Google Scholar 

  34. Tsujita K, Sugiyama S, Sumida H, Shimomura H, Yamashita T, Yamanaga K, et al. Impact of dual lipid-lowering strategy with ezetimibe and atorvastatin on coronary plaque regression in patients with percutaneous coronary intervention: the multicenter randomized controlled PRECISE-IVUS trial. J Am Coll Cardiol. 2015;66:495–507. https://doi.org/10.1016/j.jacc.2015.05.065.

    Article  PubMed  Google Scholar 

  35. Arimura T, Miura SI, Ike A, Sugihara M, Iwata A, Nishikawa H, et al. Comparison of the efficacy and safety of statin and statin/ezetimibe therapy after coronary stent implantation in patients with stable angina. J Cardiol. 2012;60(2):111–8. https://doi.org/10.1016/j.jjcc.2012.03.002.

    Article  PubMed  Google Scholar 

  36. Okada K, Iwahashi N, Endo T, Himeno H, Fukui K, Kobayashi S, et al. Long-term effects of ezetimibe-plus-statin therapy on low-density lipoprotein cholesterol levels as compared with double-dose statin therapy in patients with coronary artery disease. Atherosclerosis. 2012;224:454–6. https://doi.org/10.1016/j.atherosclerosis.2012.07.036.

    Article  CAS  PubMed  Google Scholar 

  37. Cho YK, Hur SH, Han CD, Park HS, Yoon HJ, Kim H, et al. Comparison of ezetimibe/simvastatin 10/20 mg versus atorvastatin 20 mg in achieving a target low density lipoprotein-cholesterol goal for patients with very high risk. Korean Circ J. 2011;41:149–53. https://doi.org/10.4070/kcj.2011.41.3.149.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Fujisue K, Yamanaga K, Nagamatsu S, Shimomura H, Yamashita T, Nakao K, et al. Effects of statin plus ezetimibe on coronary plaques in acute coronary syndrome patients with diabetes mellitus: sub-analysis of PRECISE-IVUS trial. J Atheroscler Thromb. 2020. https://doi.org/10.5551/jat.54726.

    Article  PubMed  PubMed Central  Google Scholar 

  39. Sakuma M, Toyoda S, Hashimoto R, Yazawa H, Masuyama T, Hirose S, et al. Add-on ezetimibe treatment to low-dose statins vs medium-intensity statin monotherapy in coronary artery disease patients with poorly controlled dyslipidemia. Hypertens Res. 2019;42(12):1923–31. https://doi.org/10.1038/s41440-019-0308-5.

    Article  CAS  PubMed  Google Scholar 

  40. Lee JH, Kang HJ, Kim HS, Sohn DW, Oh BH, Park YB. Effects of ezetimibe/simvastatin 10/20 mg vs. atorvastatin 20 mg on apolipoprotein B/apolipoprotein A1 in Korean patients with type 2 diabetes mellitus: results of a randomized controlled trial. Am J Cardiovasc Drugs. 2013;13:343–51. https://doi.org/10.1007/s40256-013-0031-6.

    Article  CAS  PubMed  Google Scholar 

  41. Zubaid M, Shakir DK, Bazargani N, Binbrek A, Gopal R, Al-Tamimi O, et al. Effect of ezetimibe coadministration with simvastatin in a Middle Eastern population: a prospective, multicentre, randomized, double-blind, placebo-controlled trial. J Cardiovasc Med. 2008;9(7):688–93. https://doi.org/10.2459/JCM.0b013e3282f3a1b1.

    Article  Google Scholar 

  42. Silverman MG, Ference BA, Im K, Wiviott SD, Giugliano RP, Grundy SM, et al. Association between lowering LDL-C and cardiovascular risk reduction among different therapeutic interventions: a systematic review and meta-analysis. JAMA. 2016;316:1289–97. https://doi.org/10.1001/jama.2016.13985.

    Article  CAS  PubMed  Google Scholar 

  43. Navarese EP, Robinson JG, Kowalewski M, Kołodziejczak M, Andreotti F, Bliden K, et al. Association between baseline LDL-C level and total and cardiovascular mortality after LDL-C lowering: a systematic review and meta-analysis. JAMA. 2018;319:1566–79. https://doi.org/10.1001/jama.2018.2525.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Lorenzi M, Ambegaonkar B, Baxter CA, Jansen J, Zoratti MJ, Davies G. Ezetimibe in high-risk, previously treated statin patients: a systematic review and network meta-analysis of lipid efficacy. Clin Res Cardiol. 2019;108:487–509. https://doi.org/10.1007/s00392-018-1379-z.

    Article  PubMed  Google Scholar 

  45. Cholesterol Treatment Trialists Collaboration, Mihaylova B, Emberson J, Blackwell L, Keech A, Simes J, Barnes EH, et al. The effects of lowering LDL cholesterol with statin therapy in people at low risk of vascular disease: meta-analysis of individual data from 27 randomised trials. Lancet. 2012;380:581–90. https://doi.org/10.1016/S0140-6736(12)60367-5.

    Article  CAS  Google Scholar 

  46. Wu FL, Wang J, Ho W, Chou CH, Wu YJ, Choo DW, et al. Effectiveness of a combination of ezetimibe and statins in patients with acute coronary syndrome and multiple comorbidities: a 6-year population-based cohort study. Int J Cardiol. 2017;233:43–51. https://doi.org/10.1016/j.ijcard.2017.02.006.

    Article  PubMed  Google Scholar 

  47. Dai YY, Zhang HS, Zhang XG, Guan QG, Gao Y, Li YZ, et al. Statin-ezetimibe versus statin lipid-lowering therapy in patients with acute coronary syndromes undergoing percutaneous coronary intervention. J Thorac Dis. 2017;9:1345. https://doi.org/10.21037/jtd.2017.05.46.

    Article  PubMed  PubMed Central  Google Scholar 

  48. Huang Z, Li Q, Ye W, Zhang Q, Li X. Efficacy and safety of ezetimibe in combination with atorvastatin for acute coronary syndrome patients accompanied with type 2 diabetes: a single-center non-randomized cohort study. Chem Pharm Bull. 2019;67:419–25. https://doi.org/10.1248/cpb.c18-00685.

    Article  CAS  Google Scholar 

  49. FDA Approves Bempedoic Acid-Ezetimibe Combination for ASCVD, Heterozygous FH-Medscape. 2020. https://www.medscape.com/viewarticle/925808.

  50. Zhu Y, Hu H, Yang J, Yao Q, Xu H, Yu Y, et al. The efficacy and safety of statin in combination with ezetimibe compared with double-dose statin in patients with high cardiovascular risk: a meta-analysis. Bosn J Basic Med Sci. 2020;20(2):169–82.

    PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. Institute of Public Health, College of Medicine and Health Sciences, UAE University, Al Ain, United Arab Emirates

    Akshaya Srikanth Bhagavathula

  2. Gastroenterology Department, Sheikh Shakhbout Medical City, Abu Dhabi, United Arab Emirates

    Wafa Ali Aldhaleei

  3. Cardiology Department, Sheikh Shakhbout Medical City, Abu Dhabi, United Arab Emirates

    Nadya Obaid Al Matrooshi

  4. Department of Community Nutrition, Student Research Committee, Faculty of Nutrition and Food Technology, National Nutrition and Food Technology Research Institute, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Jamal Rahmani

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  1. Akshaya Srikanth Bhagavathula
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Contributions

ASB, JR, WAA, and NOAM designed the study; ASB, NOAM, and WAA independently carried out the literature search and screening of the articles; JR and ASB analysed the data; ASB and WAA wrote the manuscript; and all authors read and approved the final paper.

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Correspondence to Akshaya Srikanth Bhagavathula.

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Akshaya Srikanth Bhagavathula, Wafa Ali Aldhaleei, Nadya Obaid Al Matrooshi, and Jamal Rahmani declare no conflicts of interest.

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Bhagavathula, A.S., Aldhaleei, W.A., Al Matrooshi, N.O. et al. Efficacy of Statin/Ezetimibe for Secondary Prevention of Atherosclerotic Cardiovascular Disease in Asian Populations: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Clin Drug Investig 40, 809–826 (2020). https://doi.org/10.1007/s40261-020-00951-1

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