Single-pill combination therapy in the treatment of dyslipidemia and in the prevention of cardiovascular events Review article
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Published:
Jun 30, 2025
Keywords:
dyslipidaemia, hypercholesterolaemia, LDL-cholesterol, fixed dose, single-pill
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Abstract
Cardiovascular diseases are main cause of deaths worldwide and in Poland. Dyslipidemia remains main reversable risk factor for cardiovascular diseases. The main elements of the treatment involves high-intensivity statins in maximally tolerated doses, ezetimibe and PCSK-9 inhibitors. Development of single-pill combination therapy including statin and ezetimibe increases compliance and in contrast to separate pills allows for amplification of hypolipemic effect for about 15%. Initiation therapy with single-pill fixed dose combination therapy was already proposed for treatment of patients post-acute coronary syndrome (European Society of Cardiology guidelines, II B). However, in regards to current state of knowledge, the faster and the lower the LDL-cholesterol the better prognosis achieved by the patients. Thus, the initiation of the therapy with single-pill fixed dose combination therapy may be considered in justified cases (especially among patients with high/very-high risk when LDL-cholesterol is higher than 120 mg/dl).
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How to Cite
Muszyński, P., & Tomaszuk-Kazberuk, A. (2025). Single-pill combination therapy in the treatment of dyslipidemia and in the prevention of cardiovascular events. Medycyna Faktow (J EBM), 18(2(67), 190-195. https://doi.org/10.24292/01.MF.0225.04
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References
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7. Kim B-K, Hong S-J, Lee Y-J et al. Long-term efficacy and safety of moderate-intensity statin with ezetimibe combination therapy versus high-intensity statin monotherapy in patients with atherosclerotic cardiovascular disease (RACING): a randomised, open-label, non-inferiority trial. The Lancet. 2022; 400(10349): 380-90.
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9. Lee SA, Hong SJ, Sung JH et al. Effectiveness of low-intensity atorvastatin 5 mg and ezetimibe 10 mg combination therapy compared with moderate-intensity atorvastatin 10 mg monotherapy: A randomized, double-blinded, multi-center, phase III study. Medicine (Baltimore). 2023; 102(47): e36122.
10. Otsuki H, Arashi H, Yamaguchi J et al. Effect of Ezetimibe + Pitavastatin on Cardiovascular Outcomes in Patients with ST-Segment Elevation Myocardial Infarction (from the HIJ-PROPER Study). Am J Cardiol. 2020; 132: 15-21.
11. Oyama K, Giugliano RP, Blazing MA et al. Baseline Low-Density Lipoprotein Cholesterol and Clinical Outcomes of Combining Ezetimibe With Statin Therapy in IMPROVE-IT. J Am Coll Cardiol. 2021; 78(15): 1499-507.
12. Farnier M, Santos RD, Cosin-Sales J et al. Projected impact of treatment intensification with statin, ezetimibe, and statin plus ezetimibe fixe-dose combination on MACE across six countries. Eur J Prev Cardiol. 2022; 29(17): 2264-71.
13. Tsujita K, Sugiyama S, Sumida H 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(5): 495-507.
14. Byrne RA, Rossello X, Coughlan JJ et al. 2023 ESC Guidelines for the management of acute coronary syndromes: Developed by the task force on the management of acute coronary syndromes of the European Society of Cardiology (ESC). Eur Heart J. 2023; 44(38): 3720-826.
15. Vrints C, Andreotti F, Koskinas KC et al. 2024 ESC Guidelines for the management of chronic coronary syndromes: Developed by the task force for the management of chronic coronary syndromes of the European Society of Cardiology (ESC) Endorsed by the European Association for Cardio-Thoracic Surgery (EACTS). Eur Heart J. 2024; 45(36): 3415-537.
16. Perez de Isla L, Liberopoulos E, Dovizio M et al. Differential Adherence to Free and Single-Pill Combination of Rosuvastatin/Ezetimibe: Findings from a Real-World Analysis in Italy. Adv Ther. 2024; 41(8): 3407-18.
17. Rea F, Savaré L, Corrao G et al. Adherence to Lipid-Lowering Treatment by Single-Pill Combination of Statin and Ezetimibe. Adv Ther. 2021; 38(10): 5270-85.
18. Ray KK, Reeskamp LF, Laufs U et al. Combination lipid-lowering therapy as first-line strategy in very high-risk patients. Eur Heart J. 2021; 43(8): 830-3.
19. Banach M, Reiner Ž, Surma S et al. 2024 Recommendations on the Optimal Use of Lipid-Lowering Therapy in Established Atherosclerotic Cardiovascular Disease and Following Acute Coronary Syndromes: A Position Paper of the International Lipid Expert Panel (ILEP). Drugs. 2024; 84(12): 1541-77.
2. Jankowski P, Topór-Mądry R, Gąsior M et al. Management and predictors of clinical events in 75 686 patients with acute myocardial infarction. Polish Heart Journal (Kardiologia Polska). 2022; 80(4): 468-75.
3. Banach M, Burchardt P, Chlebus K et al. Wytyczne PTL/KLRwP/PTK/ PTDL/PTD/PTNT diagnostyki i leczenia zaburzeń lipidowych w Polsce 2021. Lekarz POZ Suplement. 2021.
4. Ross E, Shah N, Leeper N. Statin Intensity or Achieved LDL? Practice-based Evidence for the Evaluation of New Cholesterol Treatment Guidelines. PloS One. 2016; 11: e0154952.
5. Katzmann JL, Sorio-Vilela F, Dornstauder E et al. Non-statin lipid-lowering therapy over time in very-high-risk patients: effectiveness of fixe-dose statin/ezetimibe compared to separate pill combination on LDL-C. Clin Res Cardiol. 2022; 111(3) 243-52.
6. Banach M, Surma S, Toth PP. 2023: The year in cardiovascular disease – the year of new and prospective lipid lowering therapies. Can we render dyslipidemia a rare disease by 2024? Arch Med Sci. 2023; 19(6): 1602-15.
7. Kim B-K, Hong S-J, Lee Y-J et al. Long-term efficacy and safety of moderate-intensity statin with ezetimibe combination therapy versus high-intensity statin monotherapy in patients with atherosclerotic cardiovascular disease (RACING): a randomised, open-label, non-inferiority trial. The Lancet. 2022; 400(10349): 380-90.
8. Lee S-J, Joo JH, Park S et al. Combination Lipid-Lowering Therapy in Patients Undergoing Percutaneous Coronary Intervention. J Am Coll Cardiol. 2023; 82(5): 401-10.
9. Lee SA, Hong SJ, Sung JH et al. Effectiveness of low-intensity atorvastatin 5 mg and ezetimibe 10 mg combination therapy compared with moderate-intensity atorvastatin 10 mg monotherapy: A randomized, double-blinded, multi-center, phase III study. Medicine (Baltimore). 2023; 102(47): e36122.
10. Otsuki H, Arashi H, Yamaguchi J et al. Effect of Ezetimibe + Pitavastatin on Cardiovascular Outcomes in Patients with ST-Segment Elevation Myocardial Infarction (from the HIJ-PROPER Study). Am J Cardiol. 2020; 132: 15-21.
11. Oyama K, Giugliano RP, Blazing MA et al. Baseline Low-Density Lipoprotein Cholesterol and Clinical Outcomes of Combining Ezetimibe With Statin Therapy in IMPROVE-IT. J Am Coll Cardiol. 2021; 78(15): 1499-507.
12. Farnier M, Santos RD, Cosin-Sales J et al. Projected impact of treatment intensification with statin, ezetimibe, and statin plus ezetimibe fixe-dose combination on MACE across six countries. Eur J Prev Cardiol. 2022; 29(17): 2264-71.
13. Tsujita K, Sugiyama S, Sumida H 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(5): 495-507.
14. Byrne RA, Rossello X, Coughlan JJ et al. 2023 ESC Guidelines for the management of acute coronary syndromes: Developed by the task force on the management of acute coronary syndromes of the European Society of Cardiology (ESC). Eur Heart J. 2023; 44(38): 3720-826.
15. Vrints C, Andreotti F, Koskinas KC et al. 2024 ESC Guidelines for the management of chronic coronary syndromes: Developed by the task force for the management of chronic coronary syndromes of the European Society of Cardiology (ESC) Endorsed by the European Association for Cardio-Thoracic Surgery (EACTS). Eur Heart J. 2024; 45(36): 3415-537.
16. Perez de Isla L, Liberopoulos E, Dovizio M et al. Differential Adherence to Free and Single-Pill Combination of Rosuvastatin/Ezetimibe: Findings from a Real-World Analysis in Italy. Adv Ther. 2024; 41(8): 3407-18.
17. Rea F, Savaré L, Corrao G et al. Adherence to Lipid-Lowering Treatment by Single-Pill Combination of Statin and Ezetimibe. Adv Ther. 2021; 38(10): 5270-85.
18. Ray KK, Reeskamp LF, Laufs U et al. Combination lipid-lowering therapy as first-line strategy in very high-risk patients. Eur Heart J. 2021; 43(8): 830-3.
19. Banach M, Reiner Ž, Surma S et al. 2024 Recommendations on the Optimal Use of Lipid-Lowering Therapy in Established Atherosclerotic Cardiovascular Disease and Following Acute Coronary Syndromes: A Position Paper of the International Lipid Expert Panel (ILEP). Drugs. 2024; 84(12): 1541-77.