Гиполипидемическая эффективность и профиль безопасности высоких доз аторвастатина и розувастатина

Назначение высоких доз аторвастатина 80 мг / сут и розувастатина 40 мг / сут входит в стандартный алгоритм лечения больных очень высокого и высокого СС риска. Это позволяет снизить уровень атерогенного холестерина липопротеидов низкой плотности (ХС ЛНП) примерно на 50 % и уменьшить риск развития сердечно-сосудистых заболеваний. Результаты проспективных исследований с аторвастатином и розувастатином демонстрируют значительное (на 45–55 %) снижение уровня ХС ЛНП и триглицеридов (на 11–50 %). Статья посвящена анализу доказательной базы данных по аторвастатину и розувастатину в проспективных исследованиях, обзору ретроспективной базы данных исследования VOYAGER, в том числе подгрупп пациентов с сахарным диабетом 2‑го типа, лиц с гипертриглицеридемией, оценке вариабельности гиполипидемического ответа и анализу снижения риска развития сердечно-сосудистых заболеваний и их осложнений при лечении этими статинами. Розувастатин в высшей суточной дозе 40 мг / сут имеет преимущества перед аторвастатином 80 мг / сут по степени снижения уровня ХС ЛНП. Оба статина обладают большой вариабельностью по степени снижения уровня триглицеридов и оказывают минимальное влияние на уровень холестерина липопротеидов высокой плотности. По результатам завершенных исследований розувастатин 40 мг / сут также имеет преимущества перед высокими дозами аторвастатина по переносимос­ти и безопасности.

1. Ference BA, Ginsberg HN, Graham I, Ray KK, Packard CJ, Bruckert E et al. Low-density lipoproteins cause atherosclerotic cardiovascular disease. 1. Evidence from genetic, epidemiologic, and clinical studies. A consensus statement from the European Atherosclerosis Society Consensus Panel. European Heart Journal. 2017;38(32):2459–72. DOI: 10.1093/eurheartj/ehx144

2. 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. Journal of the American College of Cardiology. 2019;73(24):e285–350. DOI: 10.1016/j.jacc.2018.11.003

3. Mach F, Baigent C, Catapano AL, Koskinas KC, Casula M, Badimon L et al. 2019 ESC/EAS guidelines for the management of dyslipidaemias: Lipid modification to reduce cardiovascular risk. Atherosclerosis. 2019;290(1):140–205. DOI: 10.1016/j.atherosclerosis.2019.08.014

4. Visseren FLJ, Mach F, Smulders YM, Carballo D, Koskinas KC, Bäck M et al. 2021 ESC Guidelines on cardiovascular disease prevention in clinical practice. European Heart Journal. 2021;42(34):3227–337. DOI: 10.1093/eurheartj/ehab484

5. Cannon CP, Blazing MA, Giugliano RP, McCagg A, White JA, Theroux P et al. Ezetimibe Added to Statin Therapy after Acute Coronary Syndromes. New England Journal of Medicine. 2015;372(25):2387–97. DOI: 10.1056/NEJMoa1410489

6. Sabatine MS, Giugliano RP, Keech AC, Honarpour N, Wiviott SD, Murphy SA et al. Evolocumab and Clinical Outcomes in Patients with Cardiovascular Disease. New England Journal of Medicine. 2017;376(18):1713–22. DOI: 10.1056/NEJMoa1615664

7. Schwartz GG, Steg PG, Szarek M, Bhatt DL, Bittner VA, Diaz R et al. Alirocumab and Cardiovascular Outcomes after Acute Coronary Syndrome. New England Journal of Medicine. 2018;379(22):2097–107. DOI: 10.1056/NEJMoa1801174

8. Schwartz GG, Gabriel Steg P, Bhatt DL, Bittner VA, Diaz R, Goodman SG et al. Clinical Efficacy and Safety of Alirocumab After Acute Coronary Syndrome According to Achieved Level of Low-Density Lipoprotein Cholesterol: A Propensity Score–Matched Analysis of the ODYSSEY OUTCOMES Trial. Circulation. 2021;143(11):1109–22. DOI: 10.1161/CIRCULATIONAHA.120.049447

9. Cannon CP, Steinberg BA, Murphy SA, Mega JL, Braunwald E. Meta-Analysis of Cardiovascular Outcomes Trials Comparing Intensive Versus Moderate Statin Therapy. Journal of the American College of Cardiology. 2006;48(3):438–45. DOI: 10.1016/j.jacc.2006.04.070

10. Оганов Р.Г., Кухарчук В.В., Арутюнов Г.П., Галявич А.С., Гуревич В.С., Дупляков Д.В. и др. Сохраняющиеся нарушения показателей липидного спектра у пациентов с дислипидемией, получающих статины, в реальной клинической практике в Российской Федерации (российская часть исследования DYSIS). Кардиоваскулярная терапия и профилактика. 2012;11(4):70-8. DOI: 10.15829/1728-8800-2012-4-70-78

11. Ершова А.И., Мешков А.Н., Якушин С.С., Лукьянов М.М., Мосейчук К.А., Марцевич С.Ю. и др. Диагностика и лечение больных с выраженной гиперхолестеринемией в реальной амбулаторноклинической практике (по данным регистра РЕКВАЗА). Рациональная фармакотерапия в кардиологии. 2014;10(6):612-6. DOI: 10.20996/1819-6446-2014-10-6-612-616

12. Ахмеджанов Н.М., Небиеридзе Д.В., Сафарян А.С., Выгодин В.А., Шураев А.Ю., Ткачева О.Н. и др. Анализ распространенности гиперхолестеринемии в условиях амбулаторной практики (по данным исследования АРГО): часть I. Рациональная фармакотерапия в кардиологии. 2015;11(3):253-60. DOI: 10.20996/1819-6446-2015-11-3-253-260

13. Jones P, Kafonek S, Laurora I, Hunninghake D. Comparative Dose Efficacy Study of Atorvastatin Versus Simvastatin, Pravastatin, Lovastatin, and Fluvastatin in Patients With Hypercholesterolemia (The CURVES Study). The American Journal of Cardiology. 1998;81(5):582–7. DOI: 10.1016/S0002-9149(97)00965-X

14. Smilde T, van Wissen S, Awollersheim H, Trip M, Kastelein J, Stalenhoef A. Effect of aggressive versus conventional lipid lowering on atherosclerosis progression in familial hypercholesterolemia (ASAP): a prospective, randomised, double-blind trial. The Lancet. 2001;357(9256):577–81. DOI: 10.1016/S0140-6736(00)04053-8

15. Pitt B, Waters D, Brown WV, van Boven AJ, Schwartz L, Title LM et al. Aggressive Lipid-Lowering Therapy Compared with Angioplasty in Stable Coronary Artery Disease. New England Journal of Medicine. 1999;341(2):70–6. DOI: 10.1056/NEJM199907083410202

16. Schwartz GG, Olsson AG, Ezekowitz MD, Ganz P, Oliver MF, Waters D et al. Effects of Atorvastatin on Early Recurrent Ischemic Events in Acute Coronary SyndromesThe MIRACL Study: A Randomized Controlled Trial. JAMA. 2001;285(13):1711–8. DOI: 10.1001/jama.285.13.1711

17. Amarenco P, Bogousslavsky J, Callahan A 3rd, Goldstein LB, Hennerici M, Rudolph AE et al. High-Dose Atorvastatin after Stroke or Transient Ischemic Attack. New England Journal of Medicine. 2006;355(6):549–59. DOI: 10.1056/NEJMoa061894

18. Cannon CP, Braunwald E, McCabe CH, Rader DJ, Rouleau JL, Belder R et al. Intensive versus Moderate Lipid Lowering with Statins after Acute Coronary Syndromes. Pravastatin or Atorvastatin Evaluation and Infection Therapy – Thrombolysis in Myocardial Infarction 22. (PROVE-IT TIMI 22). New England Journal of Medicine. 2004;350(15):1495–504. DOI: 10.1056/NEJMoa040583

19. Nissen SE, Tuzcu EM, Schoenhagen P, Brown BG, Ganz P, Vogel RA et al. Effect of Intensive Compared With Moderate LipidLowering Therapy on Progression of Coronary Atherosclerosis: A Randomized Controlled Trial. JAMA. 2004;291(9):1071–80. DOI: 10.1001/jama.291.9.1071

20. LaRosa JC, Grundy SM, Waters DD, Shear C, Barter P, Fruchart J-C et al. Intensive Lipid Lowering with Atorvastatin in Patients with Stable Coronary Disease. New England Journal of Medicine. 2005;352(14):1425–35. DOI: 10.1056/NEJMoa050461

21. Pedersen TR, Faergeman O, Kastelein JJ, Olsson AG, Tikkanen MJ, Holme I et al. High-Dose Atorvastatin vs Usual-Dose Simvastatin for Secondary Prevention After Myocardial InfarctionThe IDEAL Study: A Randomized Controlled Trial. JAMA. 2005;294(19):2437–45. DOI: 10.1001/jama.294.19.2437

22. Schuster H, Fox JC. Investigating cardiovascular risk reduction – the Rosuvastatin GALAXY ProgrammeTM. Expert Opinion on Pharmacotherapy. 2004;5(5):1187–200. DOI: 10.1517/14656566.5.5.1187

23. Jones PH, Davidson MH, Stein EA, Bays HE, McKenney JM, Miller E et al. Comparison of the efficacy and safety of rosuvastatin versus atorvastatin, simvastatin, and pravastatin across doses (STELLAR*Trial). The American Journal of Cardiology. 2003;92(2):152–60. DOI: 10.1016/S0002-9149(03)00530-7

24. Berne C, Siewert-Delle A, the URANUS study investigators. Comparison of rosuvastatin and atorvastatin for lipid lowering in patients with type 2 diabetes mellitus: results from the URANUS study. Cardiovascular Diabetology. 2005;4(1):7. DOI: 10.1186/1475-2840-4-7

25. Crouse JR, Raichlen JS, Riley WA, Evans GW, Palmer MK, O’Leary DH et al. Effect of Rosuvastatin on Progression of Carotid Intima-Media Thickness in Low-Risk Individuals With Subclinical Atherosclerosis: The METEOR Trial. JAMA. 2007;297(12):1344–53. DOI: 10.1001/jama.297.12.1344

26. Nicholls SJ, Brandrup-Wognsen G, Palmer M, Barter PJ. Metaanalysis of Comparative Efficacy of Increasing Dose of Atorvastatin Versus Rosuvastatin Versus Simvastatin on Lowering Levels of Atherogenic Lipids (from VOYAGER). The American Journal of Cardiology. 2010;105(1):69–76. DOI: 10.1016/j.amjcard.2009.08.651

27. Barter PJ, Brandrup-Wognsen G, Palmer MK, Nicholls SJ. Effect of statins on HDL-C: a complex process unrelated to changes in LDL-C: analysis of the VOYAGER Database. Journal of Lipid Research. 2010;51(6):1546–53. DOI: 10.1194/jlr.P002816

28. Karlson BW, Barter PJ, Palmer MK, Lundman P, Nicholls SJ. Comparison of the effects of different statins and doses on lipid levels in patients with diabetes: Results from VOYAGER. Nutrition, Metabolism and Cardiovascular Diseases. 2012;22(9):697–703. DOI: 10.1016/j.numecd.2012.03.003

29. Karlson BW, Palmer MK, Nicholls SJ, Lundman P, Barter PJ. A VOYAGER Meta-Analysis of the Impact of Statin Therapy on Low-Density Lipoprotein Cholesterol and Triglyceride Levels in Patients With Hypertriglyceridemia. The American Journal of Cardiology. 2016;117(9):1444–8. DOI: 10.1016/j.amjcard.2016.02.011

30. Karlson BW, Wiklund O, Palmer MK, Nicholls SJ, Lundman P, Barter PJ. Variability of low-density lipoprotein cholesterol response with different doses of atorvastatin, rosuvastatin, and simvastatin: results from VOYAGER. European Heart Journal - Cardiovascular Pharmacotherapy. 2016;2(4):212–7. DOI: 10.1093/ehjcvp/pvw006

31. Palmer MK, Nicholls SJ, Lundman P, Barter PJ, Karlson BW. Achievement of LDL-C goals depends on baseline LDL-C and choice and dose of statin: An analysis from the VOYAGER database. European Journal of Preventive Cardiology. 2013;20(6):1080–7. DOI: 10.1177/2047487313489875

32. Karlson BW, Palmer MK, Nicholls SJ, Lundman P, Barter PJ. Doses of rosuvastatin, atorvastatin and simvastatin that induce equal reductions in LDL-C and non-HDL-C: Results from the VOYAGER meta-analysis. European Journal of Preventive Cardiology. 2016;23(7):744–7. DOI: 10.1177/2047487315598710

33. Karlson BW, Palmer MK, Nicholls SJ, Lundman P, Barter PJ. To what extent do high-intensity statins reduce low-density lipoprotein cholesterol in each of the four statin benefit groups identified by the 2013 American College of Cardiology/American Heart Association guidelines? A VOYAGER meta-analysis. Atherosclerosis. 2015;241(2):450–4. DOI: 10.1016/j.atherosclerosis.2015.05.029

34. Karlson BW, Palmer MK, Nicholls SJ, Barter PJ, Lundman P. Effects of age, gender and statin dose on lipid levels: Results from the VOYAGER meta-analysis database. Atherosclerosis. 2017;265:54–9. DOI: 10.1016/j.atherosclerosis.2017.08.014

35. Karlson BW, Nicholls SJ, Lundman P, Barter PJ, Palmer MK. Modeling Statin-Induced Reductions of Cardiovascular Events in Primary Prevention: A VOYAGER Meta-Analysis. Cardiology. 2018;140(1):30–4. DOI: 10.1159/000488311

36. Stein EA, Lane M, Laskarzewski P. Comparison of Statins in Hypertriglyceridemia. The American Journal of Cardiology. 1998;81(4):66B-69B. DOI: 10.1016/S0002-9149(98)00041-1

37. Stone NJ, Robinson JG, Lichtenstein AH, Bairey Merz CN, Blum CB, Eckel RH et al. 2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults. Journal of the American College of Cardiology. 2014;63(25):2889–934. DOI: 10.1016/j.jacc.2013.11.002

38. Heart Protection Study Collaborative Group. MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20 536 high-risk individuals: a randomised placebocontrolled trial. The Lancet. 2002;360(9326):7–22. DOI: 10.1016/S0140-6736(02)09327-3

39. Ridker PM, Danielson E, Fonseca FAH, Genest J, Gotto AM, Kastelein JJP et al. Rosuvastatin to Prevent Vascular Events in Men and Women with Elevated C-Reactive Protein. New England Journal of Medicine. 2008;359(21):2195–207. DOI: 10.1056/NEJMoa0807646

40. Taguchi I, Iimuro S, Iwata H, Takashima H, Abe M, Amiya E et al. High-Dose Versus Low-Dose Pitavastatin in Japanese Patients With Stable Coronary Artery Disease (REAL-CAD): A Randomized Superiority Trial. Circulation. 2018;137(19):1997–2009. DOI: 10.1161/CIRCULATIONAHA.117.032615

41. Grundy SM, Cleeman JI, Merz CNB, Brewer HB, Clark LT, Hunninghake DB et al. A Summary of Implications of Recent Clinical Trials for the National Cholesterol Education Program Adult Treatment Panel III Guidelines. Arteriosclerosis, Thrombosis, and Vascular Biology. 2004;24(8):1329–30. DOI: 10.1161/01.ATV.0000139012.45265.e0

42. Holdgate GA, Ward WHJ, McTaggart F. Molecular mechanism for inhibition of 3-hydroxy-3-methylglutaryl CoA (HMG-CoA) reductase by rosuvastatin. Biochemical Society Transactions. 2003;31(3):528–31. DOI: 10.1042/bst0310528

43. Sattar N, Preiss D, Murray HM, Welsh P, Buckley BM, de Craen AJ et al. Statins and risk of incident diabetes: a collaborative meta-analysis of randomised statin trials. The Lancet. 2010;375(9716):735–42. DOI: 10.1016/S0140-6736(09)61965-6

44. Leiter LA, Rosenson RS, Stein E, Reckless JPD, Schulte K-L, Schleman M et al. Efficacy and safety of rosuvastatin 40mg versus atorvastatin 80 mg in high-risk patients with hypercholesterolemia: Results of the POLARIS study. Atherosclerosis. 2007;194(2):e154–64. DOI: 10.1016/j.atherosclerosis.2006.12.001

45. Stein B, Ward T, Hale G, Lyver E. Safety of High-Intensity Statins in the Veteran Population: Atorvastatin 40 to 80 mg Compared With Rosuvastatin 20 to 40 mg. Annals of Pharmacotherapy. 2020;54(5):405–13. DOI: 10.1177/1060028019888487