Combination therapy with atorvastatin and ezetimibe – its place in contemporary lipidology Review article
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Published:
Nov 30, 2025
Keywords:
dyslipidaemia, atorvastatin, ezetimibe, combination therapy
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Abstract
Hypercholesterolaemia represents the most prevalent modifiable risk factor for cardiovascular disease in Poland, with only a small proportion of patients achieving target LDL cholesterol levels. Atorvastatin, a potent statin, effectively lowers LDL cholesterol and significantly reduces the incidence of cardiovascular events such as myocardial infarction and stroke. Its pleiotropic effects include endothelial improvement, anti-inflammatory action, and renal protection. The addition of ezetimibe to statin therapy produces an additional 20–25% reduction in LDL cholesterol concentrations without increasing adverse effects. Combination therapy with atorvastatin and ezetimibe decreases all-cause and cardiovascular mortality as well as the occurrence of major adverse cardiovascular events. This therapeutic approach is particularly indicated in patients at high and very high cardiovascular risk, especially those with diabetes mellitus, chronic kidney disease, or intolerance to high-dose statin therapy, constituting a fundamental element of contemporary lipid management.
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Surma, S., Holecki, M., & Barylski, M. (2025). Combination therapy with atorvastatin and ezetimibe – its place in contemporary lipidology. Medycyna Faktow (J EBM), 18(3(68), 360-366. https://doi.org/10.24292/01.MF.0325.04
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References
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14. Sever PS, Dahlof B, Poulter NR et al. Prevention of coronary and stroke events with atorvastatin in hypertensive patients who have average or lower-than-average cholesterol concentrations, in the Anglo-Scandinavian Cardiac Outcomes Trial – Lipid Lowering Arm (ASCOT-LLA): a multicentre randomised controlled trial. Lancet. 2003; 361: 1149-58.
15. Amarenco P, Bogousslavsky J, Callahan A 3rd et al.; for the Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) Investigators: High-dose atorvastatin after stroke or transient ischemic attack. N Engl J Med. 2006; 355: 549-59.
16. de Zeeuw D. Different renal protective effects of atorvastatin and rosuvastatin in diabetic and non-diabetic renal patients with proteinuria. Results of the PLANET trials: 2010 European Renal Association – European Dialysis and Transplant Association Congress; June 27, 2010; Munich, Germany.
17. Vogt L, Bangalore S, Fayyad R et al. Atorvastatin Has a Dose-Dependent Beneficial Effect on Kidney Function and Associated Cardiovascular Outcomes: Post Hoc Analysis of 6 Double-Blind Randomized Controlled Trials. J Am Heart Assoc. 2019; 8(9): e010827. http://doi.org/10.1161/JAHA.118.010827.
18. Surma S, Ciechanowski K. Przewlekła choroba nerek związana z otyłością – epidemiologia, patofizjologia i leczenie. Terapia. 2025; 4(448): 53-63.
19. Banach M, Jaiswal V, Ang SP et al.; Lipid and Blood Pressure Meta-analysis Collaboration (LBPMC) Group and the International Lipid Expert Panel (ILEP). Impact of Lipid-Lowering Combination Therapy With Statins and Ezetimibe vs Statin Monotherapy on the Reduction of Cardiovascular Outcomes: A Meta-analysis. Mayo Clin Proc. 2025: S0025-6196(25)00075-8. http://doi.org/10.1016/j.mayocp.2025.01.018.
20. Mach F, Koskinas KC, Roeters van Lennep JE et al.; ESC/EAS Scientific Document Group. 2025 Focused Update of the 2019 ESC/EAS Guidelines for the management of dyslipidaemias. Eur Heart J. 2025; 46(42): 4359-78. http://doi.org/10.1093/eurheartj/ehaf190.
21. Lin YC, Lai TS, Wu HY et al. Effects and Safety of Statin and Ezetimibe Combination Therapy in Patients with Chronic Kidney Disease: A Systematic Review and Meta-Analysis. Clin Pharmacol Ther. 2020; 108(4): 833-43. http://doi.org/10.1002/cpt.1859.
2. Banach M, Surma S, Kapłon-Cieślicka A et al. Position paper of the Polish Expert Group on the use of pitavastatin in the treatment of lipid disorders in Poland endorsed by the Polish Lipid Association. Arch Med Sci. 2023; 20(1): 28-42. http://doi.org/10.5114/aoms/175879.
3. Surma S, Barylski M. Dyslipidemia – leczenie hipolipemizujące „od kuchni”. Terapia 2025; 6(449): 62, 64-70.
4. Patti G, Spinoni EG, Grisafi L et al. Safety and efficacy of very low LDL-cholesterol intensive lowering: a meta-analysis and meta-regression of randomized trials. Eur Heart J Cardiovasc Pharmacother. 2023; 9(2): 138-47. http://doi.org/10.1093/ehjcvp/pvac049.
5. Yebyo HG, Aschmann HE, Kaufmann M et al. Comparative effectiveness and safety of statins as a class and of specific statins for primary prevention of cardiovascular disease: A systematic review, meta-analysis, and network meta-analysis of randomized trials with 94,283 participants. Am Heart J. 2019; 210: 18-28. http://doi.org/10.1016/j.ahj.2018.12.007.
6. Ma W, Pan Q, Pan D et al. Efficacy and Safety of Lipid-Lowering Drugs of Different Intensity on Clinical Outcomes: A Systematic Review and Network Meta-Analysis. Front Pharmacol. 2021; 12: 713007. http://doi.org/10.3389/fphar.2021.713007.
7. Surma S, Barylski M. Leczenie hipolipemizujące – siła tkwi w… terapii skojarzonej statyna + ezetymib. Świat Medycyny i Farmacji. 2025; 4(283): 82, 84-90.
8. LaRosa JC, Grundy SM, Waters DD et al.; for the Treating to New Targets (TNT) Investigators. Intensive lipid lowering with atorvastatin in patients with stable coronary disease. N Eng J Med. 2005; 352: 1425-35.
9. Atorvastatin versus Revascularisation Treatment Investigators (AVERT). Aggressive lipid lowering therapy compared with angioplasty in stable coronary artery disease. N Engl J Med. 1999; 341: 70-84.
10. Koren MJ, Hunninghake DB; ALLIANCE Investigators. Clinical outcomes in managed-care patients with coronary heart disease treated aggressively in lipid-lowering disease management clinics: the alliance study. J Am Coll Cardiol. 2004; 44: 1772-9.
11. Olsson AG, Schwartz GG, Szarek M et al. High-density lipoprotein, but not low-density lipoprotein cholesterol levels influence short term prognosis after acute coronary syndrome: results from the MIRACL trial. Eur Heart J. 2005; 26: 890-6.
12. Ray KK, Cannon CP, McCabe CH et al. Early and late benefits of high-dose atorvastatin in patients with acute coronary syndromes: results from the PROVE IT-TIMI 22 trial. J Am Coll Cardiol. 2005; 46: 1405-10.
13. Colhoun HM, Betteridge DJ, Durrington PN et al. Primary prevention of cardiovascular disease with atorvastatin in type 2 diabetes in the Collaborative Atorvastatin Diabetes Study (CARDS): multicentre randomised placebo-controlled trial. Lancet. 2004; 364: 685-96.
14. Sever PS, Dahlof B, Poulter NR et al. Prevention of coronary and stroke events with atorvastatin in hypertensive patients who have average or lower-than-average cholesterol concentrations, in the Anglo-Scandinavian Cardiac Outcomes Trial – Lipid Lowering Arm (ASCOT-LLA): a multicentre randomised controlled trial. Lancet. 2003; 361: 1149-58.
15. Amarenco P, Bogousslavsky J, Callahan A 3rd et al.; for the Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) Investigators: High-dose atorvastatin after stroke or transient ischemic attack. N Engl J Med. 2006; 355: 549-59.
16. de Zeeuw D. Different renal protective effects of atorvastatin and rosuvastatin in diabetic and non-diabetic renal patients with proteinuria. Results of the PLANET trials: 2010 European Renal Association – European Dialysis and Transplant Association Congress; June 27, 2010; Munich, Germany.
17. Vogt L, Bangalore S, Fayyad R et al. Atorvastatin Has a Dose-Dependent Beneficial Effect on Kidney Function and Associated Cardiovascular Outcomes: Post Hoc Analysis of 6 Double-Blind Randomized Controlled Trials. J Am Heart Assoc. 2019; 8(9): e010827. http://doi.org/10.1161/JAHA.118.010827.
18. Surma S, Ciechanowski K. Przewlekła choroba nerek związana z otyłością – epidemiologia, patofizjologia i leczenie. Terapia. 2025; 4(448): 53-63.
19. Banach M, Jaiswal V, Ang SP et al.; Lipid and Blood Pressure Meta-analysis Collaboration (LBPMC) Group and the International Lipid Expert Panel (ILEP). Impact of Lipid-Lowering Combination Therapy With Statins and Ezetimibe vs Statin Monotherapy on the Reduction of Cardiovascular Outcomes: A Meta-analysis. Mayo Clin Proc. 2025: S0025-6196(25)00075-8. http://doi.org/10.1016/j.mayocp.2025.01.018.
20. Mach F, Koskinas KC, Roeters van Lennep JE et al.; ESC/EAS Scientific Document Group. 2025 Focused Update of the 2019 ESC/EAS Guidelines for the management of dyslipidaemias. Eur Heart J. 2025; 46(42): 4359-78. http://doi.org/10.1093/eurheartj/ehaf190.
21. Lin YC, Lai TS, Wu HY et al. Effects and Safety of Statin and Ezetimibe Combination Therapy in Patients with Chronic Kidney Disease: A Systematic Review and Meta-Analysis. Clin Pharmacol Ther. 2020; 108(4): 833-43. http://doi.org/10.1002/cpt.1859.