Место ингибиторов ГМГ-КоА-редуктазы в первичной профилактике сердечно-сосудистых заболеваний: соотношение пользы и риска
Изможерова Н.В., Косташ В.А., Шамбатов М.А., Попов А.А.
Систематический обзор посвящен анализу места статинов в первичной профилактике сердечно-сосудистых заболеваний (ССЗ). Проанализированы современные международные рекомендации и доказательная база, демонстрирующая эффективность терапии в снижении риска серьезных нежелательных сердечно-сосудистых событий (MACE). Особое внимание уделено дискуссионным вопросам, включая назначение статинов пациентам с промежуточным риском и лицам старше 75 лет, где соотношение пользы и рисков требует строго индивидуального подхода. Подчеркивается благоприятный профиль безопасности статинов, при этом многие субъективные побочные эффекты ассоциированы с ноцебо-феноменом, в то время как наиболее значимыми рисками являются дозозависимое повышение частоты развития сахарного диабета 2 типа и гепатотоксичность. Определение оптимальных критериев терапии, особенно в гериатрической практике, ожидается от результатов текущих масштабных исследований STAREE и PREVENTABLE.
Для цитирования: Изможерова Н.В., Косташ В.А., Шамбатов М.А., Попов А.А. Место ингибиторов ГМГ-КоА-редуктазы в первичной профилактике сердечно-сосудистых заболеваний: соотношение пользы и риска. Фарматека. 2025;32(8):128-135. DOI: https://dx.doi.org/10.18565/pharmateca.2025.8.128-135
Вклад авторов: Концепция и дизайн исследования, написание текста – Изможерова Н.В., Косташ В.А. Сбор и обработка материала – Косташ В.А., Шамбатов М.А. Редактирование – Изможерова Н.В., Попов А.А. Утверждение окончательного варианта статьи – все авторы.
Конфликт интересов: Авторы декларируют отсутствие явных и потенциальных конфликтов интересов, связанных с публикацией настоящей статьи.
Финансирование: Работа выполнена без спонсорской поддержки.
Ключевые слова
Список литературы
1. Global Cardiovascular Risk Consortium; Magnussen C., Ojeda F.M., Leong D.P. et al. Global effect of modifiable risk factors on cardiovascular disease and mortality. N Engl J Med. 2023;389(14):1273-1285. https://dx.doi.org/10.1056/NEJMoa2206916
2. Michaeli D.T., Michaeli J.C., Albers S., Boch T., Michaeli T. Established and Emerging Lipid-Lowering Drugs for Primary and Secondary Cardiovascular Prevention. Am J Cardiovasc Drugs. 2023;23(5):477–495. https://dx.doi.org/10.1007/s40256-023-00594-5
3. Ежов М.В., Кухарчук В.В., Сергиенко И.В. и др. Нарушения липидного обмена. Клинические рекомендации 2023. Российский кардиологический журнал. 2023;28(5):5471.
4. Mach F., Koskinas K.C., Roeters van Lennep J.E., et al., ESC/EAS Scientific Document Group, 2025 Focused Update of the 2019 ESC/EAS Guidelines for the management of dyslipidaemias: Developed by the task force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS), European Heart Journal, 2025;ehaf190. https://doi.org/10.1093/eurheartj/ehaf190
5. U.S. Preventive Services Task Force. Statin use for the primary prevention of cardiovascular disease in adults: preventive medication. Updated February 15, 2022. Accessed July 10, 2021. URL: https://www.uspreventiveservicestaskforce.org/uspstf/draft-update-summary/statin-use-primary-prevention-cardiovascular-disease-adults
6. Virani S.S. Statins and Primary Atherosclerotic Cardiovascular Disease Prevention-What We Know, Where We Need to Go, and Why Are We Not There Already? JAMA Netw Open. 2022;5(8):e2228538. https://dx.doi.org/10.1001/jamanetworkopen.2022.28538
7. Freeman D.J., Norrie J., Sattar N., et al. Pravastatin and the development of diabetes mellitus: evidence for a protective treatment effect in the West of Scotland Coronary Prevention Study. Circulation. 2001;103(3):357-362. https://dx.doi.org/10.1161/01.cir.103.3.357
8. Kushiro T., Mizuno K., Nakaya N., et al. Pravastatin for cardiovascular event primary prevention in patients with mild-to-moderate hypertension in the Management of Elevated Cholesterol in the Primary Prevention Group of Adult Japanese (MEGA) Study. Hypertension. 2009;53(2):135-141. https://dx.doi.org/10.1161/HYPERTENSIONAHA.108.120584
9. Hoshi R.A., Alotaibi M., Liu Y., et al. One-Year Effects of High-Intensity Statin on Bioactive Lipids: Findings From the JUPITER Trial. Arterioscler Thromb Vasc Biol. 2024;44(7):e196-e206. https://dx.doi.org/10.1161/ATVBAHA.124.321058
10. Zoungas S., Curtis A., Spark S., et al. Statins for extension of disability-free survival and primary prevention of cardiovascular events among older people: protocol for a randomised controlled trial in primary care (STAREE trial). BMJ Open. 2023;13(4):e069915. https://dx.doi.org/10.1136/bmjopen-2022-069915
11. Ibanez B., Fernandez-Ortiz A., Fernandez-Friera L., et al. Progression of Early Subclinical Atherosclerosis (PESA) Study: JACC Focus Seminar 7/8. J Am Coll Cardiol. 2021;78(2):156-179. https://dx.doi.org/10.1016/j.jacc.2021.05.011
12. Khatiwada N., Hong Z. Potential Benefits and Risks Associated with the Use of Statins. Pharmaceutics. 2024;16(2):214. https://dx.doi.org/10.3390/pharmaceutics16020214
13. Bosco E., Hsueh L., McConeghy K.W., et al. Major adverse cardiovascular event definitions used in observational analysis of administrative databases: a systematic review. BMC Med Res Methodol. 2021;21(1):241. https://dx.doi.org/10.1186/s12874-021-01440-5
14. Zhou Z., Curtis A.J., Ernst M.E., et al. Comparison of statins for primary prevention of cardiovascular disease and persistent physical disability in older adults. Eur J Clin Pharmacol. 2022;78(3):467-476. doi:10.1007/s00228-021-03239-1
15. Aebi P.S., Adam L., Haller M., et al. Rationale and design of ‘discontinuing statins in multimorbid older adults without cardiovascular disease (STREAM)’: study protocol of a randomised non-inferiority clinical trial. BMJ Open. 2025;15(5):e093833. https://dx.doi.org/10.1136/bmjopen-2024-093833
16. Baratta F., Moscucci F., Lospinuso I., et al. Lipid-Lowering Therapy and Cardiovascular Prevention in Elderly. Drugs. 2025;85(6):801-812. https://dx.doi.org/10.1007/s40265-025-02182-0
17. Montgomery S., Miedema M.D., Dodson J.A. Aspirin and statin therapy for primary prevention of cardiovascular disease in older adults. Heart. 2022;108(14):1090-1097. https://dx.doi.org/10.1136/heartjnl-2021-320154
18. Zhang X., Xing L., Jia X., et al. Comparative Lipid-Lowering/Increasing Efficacy of 7 Statins in Patients with Dyslipidemia, Cardiovascular Diseases, or Diabetes Mellitus: Systematic Review and Network Meta-Analyses of 50 Randomized Controlled Trials. Cardiovasc Ther. 2020;2020:3987065. https://dx.doi.org/10.1155/2020/3987065
19. 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. Ann Pharmacother. 2020;54(5):405-413. https://dx.doi.org/10.1177/1060028019888487
20. Aliberti M.J.R., Tavares C.A.M., Pajewski N.M. Awaiting the verdict: Statins and the road ahead for primary prevention in older adults. J Am Geriatr Soc. 2024;72(2):332-336. https://dx.doi.org/10.1111/jgs.18764
21. Yebyo H.G., Zappacosta S., Aschmann H.E., Haile S.R., Puhan M.A. Global variation of risk thresholds for initiating statins for primary prevention of cardiovascular disease: a benefit-harm balance modelling study. BMC Cardiovasc Disord. 2020;20(1):418. doi:10.1186/s12872-020-01697-6
22. Mortensen M.B., Nordestgaard B.G. Elevated LDL cholesterol and increased risk of myocardial infarction and atherosclerotic cardiovascular disease in individuals aged 70-100 years: a contemporary primary prevention cohort. Lancet. 2020;396(10263):1644-1652. https://dx.doi.org/10.1016/S0140-6736(20)32233-9
23. Strandberg T.E. Benefits and limitations of statin use in primary cardiovascular prevention: recent advances. Pol Arch Intern Med. 2022;132(5):16258. doi:10.20452/pamw.16258
24. Jun J.E., Cho IJ,. Han K., et al. Statins for primary prevention in adults aged 75 years and older: A nationwide population-based case-control study. Atherosclerosis. 2019;283:28-34. https://dx.doi.org/10.1016/j.atherosclerosis.2019.01.030
25. Orkaby A.R., Driver J.A., Ho Y.L., et al. Association of Statin Use With All-Cause and Cardiovascular Mortality in US Veterans 75 Years and Older. JAMA. 2020;324(1):68-78. https://dx.doi.org/10.1001/jama.2020.7848
26. Zhou Z., Ofori-Asenso R., Curtis A.J., et al. Association of Statin Use With Disability-Free Survival and Cardiovascular Disease Among Healthy Older Adults. J Am Coll Cardiol. 2020;76(1):17-27. https://dx.doi.org/10.1016/j.jacc.2020.05.016
27. Bergami M., Cenko E., Yoon J., et al. Statins for primary prevention among elderly men and women. Cardiovasc Res. 2022;118(14):3000-3009. https://dx.doi.org/10.1093/cvr/cvab348
28. Yourman L.C., Cenzer I.S., Boscardin W.J., et al. Evaluation of Time to Benefit of Statins for the Primary Prevention of Cardiovascular Events in Adults Aged 50 to 75 Years: A Meta-analysis. JAMA Intern Med. 2021;181(2):179-185. https://dx.doi.org/10.1001/jamainternmed.2020.6084
29. Joseph J., Pajewski N.M., Dolor R.J., et al. Pragmatic evaluation of events and benefits of lipid lowering in older adults (PREVENTABLE): Trial design and rationale. J Am Geriatr Soc. 2023;71(6):1701-1713. https://dx.doi.org/10.1111/jgs.18312
30. National Institutes of Health. A Clinical Trial of Statin Therapy for Reducing Events in the Elderly (STAREE). URL: https://clinicaltrials.gov/ct2/show/NCT02099123 Accessed February 20, 2020.
31. National Institute on Aging. Could taking statins prevent dementia, disability? URL: https://www.nih.gov/news-events/news-releases/could-taking-statins-prevent-dementia-disability Accessed February 20, 2020.
32. Moon J., Cohen Sedgh R., Jackevicius C.A. Examining the Nocebo Effect of Statins Through Statin Adverse Events Reported in the Food and Drug Administration Adverse Event Reporting System. Circ Cardiovasc Qual Outcomes. 2021;14(1):e007480. https://dx.doi.org/10.1161/CIRCOUTCOMES.120.007480
33. Grundy S.M., Vega G.L. Statin Intolerance and Noncompliance: An Empiric Approach. Am J Med. 2022;135(3):318-323. https://dx.doi.org/10.1016/j.amjmed.2021.09.014
34. Wood F.A., Howard J.P., Finegold J.A., et al. N-of-1 Trial of a Statin, Placebo, or No Treatment to Assess Side Effects. N Engl J Med. 2020;383(22):2182-2184. https://dx.doi.org/10.1056/NEJMc2031173
35. Cai T., Abel L., Langford O., et al. Associations between statins and adverse events in primary prevention of cardiovascular disease: systematic review with pairwise, network, and dose-response meta-analyses. BMJ. 2021;374:n1537. https://dx.doi.org/10.1136/bmj.n1537
36. Alzueta Istúriz N., Fernandez Gonzalez J., Echeverría Gorriti A., et al. Protocolo del estudio Estrategia de deprescripción de estatinas y ezetimiba en prevención primaria en mayores de 75 años: análisis de los resultados en salud
37. Raizner A.E., Quiñones M.A. Coenzyme Q10 for Patients With Cardiovascular Disease: JACC Focus Seminar. J Am Coll Cardiol. 2021;77(5):609-619. https://dx.doi.org/10.1016/j.jacc.2020.12.009.
38. Jaam M., Al-Naimi H.N., Haddad M.M., et al. Comparative efficacy and safety among high-intensity statins. Systematic Review and Meta-Analysis. J Comp Eff Res. 2023;12(3):e220163. https://dx.doi.org/10.57264/cer-2022-0163
39. Lembo M., Trimarco V., Izzo R., et al. Statin-induced risk of diabetes does not reduce cardiovascular benefits in primary prevention: a 6-year propensity-score matched study in a large population. Cardiovasc Diabetol. 2025;24(1):233. doi:10.1186/s12933-025-02798-2
40. Rikhi R., Shapiro M.D. Impact of Statin Therapy on Diabetes Incidence: Implications for Primary Prevention. Curr Cardiol Rep. 2024;26(12):1447-1452. https://dx.doi.org/10.1007/s11886-024-02141-3
41. Halili A., Eroglu T.E., Torp-Pedersen C., Zareini B. Statin use for primary prevention of cardiovascular disease among apparently healthy adults. Eur J Prev Cardiol. Published online June 24, 2025. doi:10.1093/eurjpc/zwaf357
42. Chopra A.K., Yadav R. Statins in primary prevention: is the enthusiasm justified? Indian Heart J. 2020;72(4):221-224. https://dx.doi.org/10.1016/j.ihj.2020.07.021
Об авторах / Для корреспонденции
Надежда Владимировна Изможерова, д.м.н., профессор, Уральский государственный медицинский университет, Екатеринбург, Россия; nadezhda_izm@mail.ru, ORCID: https://orcid.org/0000-0001-7826-9657 (автор, ответственный за переписку)В.А. Косташ, Уральский государственный медицинский университет, Екатеринбург, Россия; ORCID: https://orcid.org/0009-0004-8918-4279
М.А. Шамбатов, Уральский государственный медицинский университет, Екатеринбург, Россия; ORCID: https://orcid.org/0000-0001-7312-415X
А.А. Попов, Уральский государственный медицинский университет, Екатеринбург, Россия; ORCID: https://orcid.org/0000-0001-6216-2468



