Statins and ischemic stroke prevention and treatment

Cover Page

Cite item

Full Text


In the article on the basis of the literature and results of numerous randomized placebo controlled trials current strategies of statins usage in primary and second prevention are presented. Particular attention is devoted to efficacy and perspectives of statins in acute stroke management. Summary recommendations on the statins usage in stroke prevention and medication have been stated.

About the authors

Andrey V. Fonyakin

Research Center of Neurology

ORCID iD: 0000-0001-5452-2152
Russian Federation, Moscow, Volokolamskoe shosse,80

Lyudmila A. Geraskina

Research Center of Neurology

Author for correspondence.
ORCID iD: 0000-0002-1253-1082
Russian Federation, Moscow, Volokolamskoe shosse,80


  1. Аронов Д.М., Бубнова М.Г. Плейотропные эффекты статинов на современном этапе их изучения (фокус на аторвастатин). Часть I. Кардиосоматика 2012; 3: 55–63.
  2. Диагностика и коррекция нарушений липидного обмена с целью профилактики и лечения атеросклероза. Клинические рекомендации ВНОК. Кардиоваскулярная терапия и профилактика 2009; 8 (6). Приложение 3.
  3. Марцевич С.Ю., Кутишенко Н.П. Первичная профилактика сердечно-сосудистых осложнений: роль статинов. Рациональная фармакотерапия в кардиологии 2009; 4: 80–84.
  4. Нейропротекция: модели, механизмы, терапия. Под ред. М. Бара; пер. с англ. под ред. В.П. Зыкова, П.Р. Камчатнова. М.:Бином. Лаборатория знаний, 2011: 429.
  5. Очерки ангионеврологии. Под ред. З.А. Суслиной. М.:Издательство «Атмосфера», 2005: 368.
  6. Пирадов М.А. Интенсивная терапия инсульта: взгляд на проблему. Анн. клин. и эксперимент. неврол. 2007; 1: 17–22.
  7. Сусеков А.В., Блохин А.Б., Лугинова З.Г. и др. Статины в профилактике ишемического инсульта. Рациональная фармакотерапия в кардиологии 2013; 9: 409–416.
  8. Суслина З.А. Сосудистая патология головного мозга: итоги и перспективы. Анн. клин. и эксперимент. неврол. 2007; 1: 10–16.
  9. Фонякин А.В., Гераскина Л.А., 2012 Профилактика ишемического инсульта. Практические рекомендации. Под ред. З.А. Суслиной. М.: Спецкнига, 2012: 40.
  10. Эффективность и безопасность лекарственной терапии при первичной и вторичной профилактике сердечно-сосудистых заболеваний. Рекомендации ВНОК, 2011.Рациональная фармакотерапия в кардиологии 2011; 7 (5), приложение: 2–72.
  11. Adams R.J., Chimowitz M.I., Alpert J.S. et al. Coronary risk evaluation in patients with transient ischemic attack and ischemic stroke: a scientific statement for healthcare professionals from the Stroke Council and the Council on Clinical Cardiology of the American Heart Association/American Stroke Association. Stroke 2003; 34: 2310–2322.
  12. Amarenco P., Goldstein L.B., Szarek M. et al. Effects of intense low density lipoprotein cholesterol reduction in patients with stroke or transient ischemic attack. The Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trial. Stroke 2007; 38: 3198–3204.
  13. Amarenco P., Labreuche J., Lavallee P., Touboul P.-J. Statin in stroke prevention and carotid atherosclerosis: systematic review and metaanalysis. Stroke 2004; 35: 2902–2909.
  14. Amarenco P., Moscowitz M.A. The dynamics of statins. From event prevention to neuroprotection. Stroke 2006; 37: 294–296.
  15. Amaud C., Vellard N.R., Mach F. et al. Cholesterol-independed effects of statins in inflamation, immunomodulation and atherosclerosis. Curr drug targets cardiovasc haematol disord, 2005; 5: 127–134.
  16. Arboix A., Garcia-Eroles L., Oliveres M. et al. Pretreatment with statins improves early outcome in patients with first-ever ischaemic stroke: a pleiotropic effect of statins or a beneficial effect of hypercholesterolemia? BMS Neurology 2010; 10: 47–54.
  17. Asahi M., Huang Z., Thomas S. et al. Protective effects of statins involving both tNOS and tPA in focal cerebral ischemia. J CerebBlood Flow Metab. 2005; 25: 722-729.
  18. Baigent C., Keech A., Kearney P.M. et al. Cholesterol treatment trialists` (CTT) collaborators. Efficacy and safety of cholesterol-lowering treatment: prospective metaanalysis of data from 90 056 participants in 14 randomized trials of statins. Lancet 2005; 366: 1267–1278.
  19. Benfante R., Yano K., Hwang L.J. et al. Elevated serum cholesterol is a risk factor for both coronary heart disease and thromboembolic stroke in Hawaiian Japanese men: implications of shared risk. Stroke 1994; 25: 814–820.
  20. Biffi A., Devan W.J., Anderson Ch. D. et al. Statin treatment and functional outcome after ischemic stroke. Stroke 2011; 42: 1314–1319.
  21. Briel M., Studer M., Glass T.R. et al. Effects of statins on stroke prevention in patients with and without coronary heart disease: a metaanalysis of randomized controlled trials. Am J Med. 2004; 117: 596–606.
  22. Brugts J.J., Yetgin T., Hoeks S. et al. The benefits of statins in people without established cardiovascular disease but with cardiovascular risk factors: meta-analysis of randomized controlled trial. BMJ 2009; 338:2376.
  23. Bucher N.C., Griffith L.E., Guyatt G.H. Effect of HMGcoA reductase inhibitors on stroke: a meta-analysis of randomized, controlled studies. Ann Intern Med. 1998; 128: 89–95.
  24. Cannon C., Braunwald E., McCabe C.H. et al. Intensive versus Moderate Lipid-lowering with statins after Acute Coronary Syndromes. N Engl J Med. 2004; 350: 1495–1504.
  25. Chen J., Zhang Z.G., Li Y. et al. Statins induce angiogenesis, neurogenesis, and synaptogenesis after stroke. Ann Neurol. 2003; 53: 743–751.
  26. Chroinin D.N., Asplund K., Asberg S. et al. Statin therapy and outcome after ischemic stroke. Systematic review and meta-analysis of observation studies and randomized trials. Stroke 2013; 44: 448–456.
  27. Collins R., Armitage J., Parish S. et al. for the Heart Protection Study Collaborative Group. Effects of cholesterol-lowering with simvastatin on stroke and other major vascular events in 20536 people with cerebrovascular disease or other high-risk conditions. Lancet 2004; 363: 757–767.
  28. Delanty N., Vaughan C.J. Vascular effects of statins in stroke. Stroke 1997; 28: 2315–2320.
  29. Downs J.R., Clearfield M., Weis S. et al. Primary prevention of acute coronary events with lovastatin in men and women with average cholesterol levels. Results of AFCAPS/TexCAPS. Air force texas coronary atherosclerosis prevention study. JAMA 1998; 279: 1615–1622.
  30. Flint A.C., Kamel H., Navi B.B. et al. Statin use during ischemic stroke hospitalization is strongly associated with improved poststroke survival. Stroke 2012; 43: 147–154.
  31. Furie K.L., Kasner S.E., Adams R.J. et al. Guidelines for prevention of stroke in patients with ischemic stroke or transient ischemic attack. A guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2011; 42: 227–276.
  32. Goldstein L.B., Amarenco P., Zivin J. et al. Statin treatment and stroke outcome in the stroke prevention by aggressive reduction in cholesterol levels (SPARCL) trial. Stroke 2009; 40: 3526–3531.
  33. Goldstein L.B., Bushnell Ch.D., Adams R.J. et al. Guidelines for the primary prevention of stroke. A guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2011; 42: 517–584.
  34. Goldstein L.D., Adams R., Alberts M.J. et al. Primary prevention of ischemic stroke. Stroke 2006; 37: 1583–1633.
  35. Guidelines for the early management of patients with acute ischemic stroke from the american heart association. American Stroke Association. Stroke 2013; 44: 870–947.
  36. Hjermann I., Velve Byre K., Holme I., Leren P. Effect of diet and smoking intervention on the incidence of coronary heart disease. Report from the Oslo Study Group of a randomized trial in healthy men. Lancet 1981; 2 (8259): 1303–1310.
  37. Iso H., Jacobs D.R. Jr., Wentworth D. et al. Serum cholesterol levels and six-year mortality from stroke in 350.977 men screened for the multiple risk factor intervention trial. N Engl J Med. 1989; 320: 904–910.
  38. Kagan A., Popper J.S., Rhoads G.G. Factors related to stroke incidence in Hawaii Japanese men: the Honolulu Heart Study. Stroke 1980; 11: 14–21.
  39. Kargman D.E., Tuck C., Berglund L.F. et al. Elevated high density lipoprotein levels are more important in atherosclerotic ischemic stroke subtypes: the Northen Manhattan Stroke Study. Ann Neurol. 1998; 44:442–443.
  40. Kaste M. Statins in threatened stroke. Stroke 2003; 34: 351–353.
  41. Kawashima S., Yamashita T., Miwa Y. et al. HMG-CoA reductase inhibitor has protective effects against stroke events in stroke-prone spontaneously hypertensive rats. Stroke 2003; 34: 157–163.
  42. Laufs U., Gertz K., Huang P. et al. Atorvastatin upregulates type III nitric oxide synthase in thrombocytes, decreases platelet activation, and protects from cerebral ischemia in normocholesterolemic mice. Stroke 2000; 31: 2442–2449.
  43. Law M.R., Wald N.J., Rudnicka A.R. Quantifying effect of statins on low density lipoprotein cholesterol, ischemic heart disease and stroke: systematic review and meta-analysis. Br Med J. 2003; 16: 624–629.
  44. Leppala J.M., Virtamo J., Fogelholm R. et al. Different risk factors for different stroke subtypes: association of blood pressure, cholesterol,and antioxidants. Stroke 1999; 30: 2535–2540.
  45. Muir K.W., Lees K.R., Ford I., Davis S. Magnesium for acute stroke (intravenous magnesium efficacy in stroke trial): Randomized controlled trial. Lancet 2004; 363: 439–445.
  46. Mullard A.J., Reeves M.J., Jacobs B.S. et al. Lipid testing and lipid lowering therapy in hospitalized ischemic stroke and transient ischemic attack patients: results from a statewide stroke registry. Stroke 2006; 37:44–49.
  47. Oliver M.E. Cholesterol, coronaries, clofibrate and death. N Engl J Med. 1978; 229: 1360–1362.
  48. Ovbiagele B., Saver J.L., Starkman S. et al. Statin enhancement of collateralization in acute stroke. Neurology 2007; 68: 2129–2131.
  49. Plehn J.F., Davis B.R., Sacks F.M. Reduction of stroke incidence after myocardial infarction with pravastatin: The Colesterol and Recurrent Events (CARE) Study. Circulation 1999; 99: 216–223.
  50. Prospective Studies Collaboration. Cholesterol, diastolic blood pressure and stroke: 13 000 strokes in 450 000 people in 45 prospective cohorts. Lancet 1995; 346: 1647–1653.
  51. Qizilbash N., Jones L., Warlow C. et al. Fibrinogen and lipid concentrations as risk factors for transient ischaemic attacks and minor ischaemic strokes. BMJ 1991; 303: 605–609.
  52. Qizilbash N., Lewington S., Duffy S. et al. Cholesterol, diastolic blood pressure and stroke: 13 000 stroke in 450 000 people in 45 prospective cohorts: Prospective Studies Collaboration. Lancet 1995; 346: 1647–1653.
  53. Ridker P.M., Danielson E., Fonseca F.A. et al. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. N Engl J Med. 2008; 359: 2195–2207.
  54. Sacco R.L., Adams R., Albers G. et al. Guidelines for prevention of stroke in patients with ischemic stroke or transient ischemic attack. Stroke 2006; 37: 577–617.
  55. Scandinavian Simvastatin Survival Study Study Group.Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian simvastatin survival study (4S). Lancet 1994; 344: 1383–1389.
  56. Shepherd J., Cobbe S.M., Ford I. et al. Prevention of coronary heart disease with pravastatin in men with hypercholesterinemia. West of Scotland Coronary Prevention Study Group. N Engl J Med. 1995; 333:1301–1307.
  57. Shuaib A., Lees K.R., Lyden P. et al. NXY-059 for the treatment of acute ischemic stroke. N Engl J Med. 2007; 357: 562–571.
  58. Squizzato A., Romualdi E., Dentali F., Ageno W. Statins for acute ischemic stroke. Stroke 2012; 43: e18–e19.
  59. Taylor F., Huffman M.D., Bacedo A.F. et al. Statins for the primary prevention of cardiovascular disease. Cocharane Database Syst Rev 2013; 1: CD004816.
  60. The Heart Protection Study Coollaborative Group. MRC/BHF Heart protection study of cholesterol lowering with simvastatin in 20536 high-risk individuals: a randomized placebo-controlled trial. Lancet 2002; 360: 7–22.
  61. The LIPID Study Group. Prevention of cardiovascular events and death with pravastatin in patients with coronary heart disease and a broad range of initial cholesterol levels. N Engl J Med. 1998; 339: 1310–1349.
  62. The SPARCL Investigators. 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: 549–559.
  63. Tonelli M., Lloyd A., Clement F. et al. Efficacy of statins for primary prevention in people at low cardiovascular risk: a meta-analysis. CMAJ 2011; 183: 1189–202.
  64. Wang C.Y., Liu P.Y., Liao J.K. Pleiotropic effects of statin therapy: molecular mechanisms and clinical results. Trends Mol. Med. 2008; 14: 37–44.
  65. Wang Q., Yan J., Chen X. et al. Statins: multiple neuroprotective mechanisms in neurodegerative diseases. Exp Neurol. 2011; 230: 27–34.
  66. Wood W.G., Eckert G.P., Igbavboa U., Muller W.E. Statins and neuroprotection. A prescription to move the field forward. Ann of the New York Acad of Sciences 2010; 1199: 69–76.
  67. Zhang X., Patel A., Horibe H. et al. Cholesterol, coronary heart disease and stroke in the Asia Pacific region. Int J Epidemiol. 2003; 32:563–572.

Supplementary files

Supplementary Files

Copyright (c) 2014 Fonyakin A.V., Geraskina L.A.

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.

СМИ зарегистрировано Федеральной службой по надзору в сфере связи, информационных технологий и массовых коммуникаций (Роскомнадзор).
Регистрационный номер и дата принятия решения о регистрации СМИ: серия ПИ № ФС 77-83204 от 12.05.2022.

This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies