Internal and Emergency Medicine

, Volume 12, Issue 5, pp 679–687 | Cite as

The efficacy and safety of high-dose statins in acute phase of ischemic stroke and transient ischemic attack: a systematic review

  • Jing-xue Fang
  • Er-qiang Wang
  • Wei Wang
  • Yang Liu
  • Gang ChengEmail author


Inconsistent findings in the studies have been observed concerning the higher dose of statins use in the acute phase of ischemic stroke and transient ischemic attack (TIA). Therefore, we performed a systematic review to assess this issue. A computerized literature search in PubMed, Cochrane Library databases, and EMBASE for randomized controlled trials (RCTs) was conducted. The efficacy outcome indicators were National Institutes of Health Stroke Scale (NIHSS) score, infarct volume, and recurrence of stroke; the safety outcome indicators were intracranial hemorrhage events, cardiovascular and cerebrovascular events, and all-cause death. Pre-specified subgroup analyses were carried out. A total of seven RCTs with 1089 patients were included. Six studies reported the results of the NHISS score. A great reduction was found in NIHSS score in the statins group, and the difference is statistically significant [mean difference (MD) −1.15, 95% confidence interval (CI) −1.64 to −0.66, P < 0.00001]. However, no significant differences in the effect on recurrence of stroke [odds ratio (OR) 1.05, 95% CI 0.65–1.69, P = 0.85] (available in 3 studies), infarct volume [std. mean difference (SMD) 0.04, 95% CI −0.55 to 0.63, P = 0.89] (available in 2 studies), intracerebral hemorrhage events (OR 3.25, 95% CI 0.34–31.52, P = 0.31) (available in 2 studies), cardiovascular and cerebrovascular events (OR 0.70, 95% CI 0.35–1.43, P = 0.33) (available in 2 studies), and all-cause death (OR 1.18, 95% CI 0.60–2.35, P = 0.63) (available in 2 studies) were found. High-dose statin therapy in the acute phase of ischemic stroke and TIA significantly reduce the NIHSS score and improve short-term functional outcome without increasing related adverse events.


High-dose statins Ischemic stroke TIA Acute phase Systematic review 



Our study had no funding.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Statement of human and animal rights

All procedures in studies involving human participants are in accordance with the ethical standards of the institutional or national research committee and with the 1964 Helsinki declaration. This article does not contain any studies with animals performed by any of the author.

Informed consent

For this type of study, informed consent is not required.


  1. 1.
    Feigin VL, Lawes CM, Bennett DA, Barker-Collo SL, Parag V (2009) Worldwide stroke incidence and early case fatality reported in 56 population- based studies: a systematic review. Lancet Neurol 8:355–369CrossRefPubMedGoogle Scholar
  2. 2.
    Meschia JF, Bushnell C, Boden-Albala B et al (2014) Guidelines for the primary prevention of stroke: a statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 45:3754–3832CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Hong KS, Lee JS (2015) Statins in acute ischemic stroke: a systematic review. J Stroke 17:282–301CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Blum A (2014) HMG-CoA reductase inhibitors (statins), inflammation, and endothelial progenitor cells—new mechanistic insights of atherosclerosis. BioFactors 40:295–302CrossRefPubMedGoogle Scholar
  5. 5.
    Cimino M, Gelosa P, Gianella A, Nobili E, Tremoli E, Sironi L (2007) Statins: multiple mechanisms of action in the ischemic brain. Neuroscientist 13:208–213CrossRefPubMedGoogle Scholar
  6. 6.
    Yakusevich VV, Malygin AYu, Lychenko SV, Petrochenko AS, Kabanov AV (2012) The efficacy of high-dose simvastatin in acute period of ischemic stroke. Rational Pharmacother Cardiol 8:4–16CrossRefGoogle Scholar
  7. 7.
    Tuttolomondo A, Di Raimondo D, Pecoraro R, Maida C, Arnao V, Della Corte V, Simonetta I, Corpora F, Di Bona D, Maugeri R, Iacopino DG, Pinto A (2016) Early high-dosage atorvastatin treatment improved serum immune-inflammatory markers and functional outcome in acute ischemic strokes classified as large artery atherosclerotic stroke: a randomized trial. Medicine 95:e3186CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Heo JH, Song D, Nam HS, Kim EY, Kim YD, Lee KY, Lee KJ, Yoo J, Kim YN, Lee BC, Yoon BW, Kim JS, Investigators EUREKA (2016) Effect and safety of rosuvastatin in acute ischemic stroke. J Stroke 18:87–95CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Muscari A, Puddu GM, Santoro N, Serafini C, Cenni A, Rossi V, Zoli M (2011) The atorvastatin during ischemic stroke study: a pilot randomized controlled trial. Clin Neuropharmacol 34:141–147CrossRefPubMedGoogle Scholar
  10. 10.
    Tziomalos K, Giampatzis V, Bouziana SD, Spanou M, Kostaki S, Papadopoulou M, Angelopoulou SM, Konstantara F, Savopoulos C, Hatzitolios AI (2015) Comparative effects of more versus less aggressive treatment with statins on the long-term outcome of patients with acute ischemic stroke. Atherosclerosis 243:65–70CrossRefPubMedGoogle Scholar
  11. 11.
    Moher D, Liberati A, Tetzlaff J, Altman DG, PRISMA Group (2009) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. BMJ 339:b2535CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Higgins JPT, Green S (2011) Cochrane handbook for systematic reviews of interventions version 5.1.0 updated March 2011. The Cochrane Collaboration 2011. Accessed 06 June 2016
  13. 13.
    Beer C, Blacker D, Bynevelt M, Hankey GJ, Puddey IB (2012) A randomized placebo controlled trial of early treatment of acute ischemic stroke with atorvastatin and irbesartan. Int J Stroke 7:104–111CrossRefPubMedGoogle Scholar
  14. 14.
    Montaner J, Chacón P, Krupinski J, Rubio F, Millán M, Molina CA, Hereu P, Quintana M, Alvarez-Sabín J (2008) Simvastatin in the acute phase of ischemic stroke: a safety and efficacy pilot trial. Eur J Neurol 15:82–90CrossRefPubMedGoogle Scholar
  15. 15.
    Kennedy J, Hill MD, Ryckborst KJ, Eliasziw M, Demchuk AM, Buchan AM, Investigators FASTER (2007) Fast assessment of stroke and transient ischaemic attack to prevent early recurrence (FASTER): a randomised controlled pilot trial. Lancet Neurol 6:961–969CrossRefPubMedGoogle Scholar
  16. 16.
    Schneider DJ, Ricci MA, Taatjes DJ et al (1997) Changes in arterial expression of fibrinolytic system proteins inatherogenesis. Arterioscler Thromb Vasc Biol 17:3294–3301CrossRefPubMedGoogle Scholar
  17. 17.
    Goldstein LB, Amarenco P, Zivin J et al (2009) Statin treatment and stroke outcome in the Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trial. Stroke 40:3526–3531CrossRefPubMedGoogle Scholar
  18. 18.
    Arboix A, García-Eroles L, Oliveres M, Targa C, Balcells M, Massons J (2010) Pretreatment with statins improves early outcome in patients with first-ever ischaemic stroke: a pleiotropic effect of statins or a beneficial effect of hypercholesterolemia? BMC Neurol 10:47CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Athyros VG, Kakafika AI, Tziomalos K, Karagiannis A, Mikhailidis DP (2009) Pleiotropic effects of statins—clinical evidence. Curr Pharm Des 15:479–489CrossRefPubMedGoogle Scholar
  20. 20.
    Cannon CP, Steinberg BA, Murphy SA, Mega JL, Braunwald E (2006) Meta-analysis of cardiovascular outcomes trials comparing intensive versus moderate statin therapy. J Am Coll Cardiol 48:438–445CrossRefPubMedGoogle Scholar
  21. 21.
    Fernándezde Bobadilla J, Moreno R, Fernández C, Martínez A, Sánchez-Maestre C, Ezpeleta-Echevarri D (2009) Effect of intensive treatment with atorvastatin versus standard doses of statins on the risk of stroke. A meta-analysis from five randomized trials including 25,709 patients. Revue Neurol 48:561–565Google Scholar
  22. 22.
    Josan K, Majumdar SR, McAlister FA (2008) The efficacy and safety of intensive statin therapy: a meta-analysis of randomized trials. Can Med Assoc J 178:576–584CrossRefGoogle Scholar
  23. 23.
    de Vries FM, Kolthof J, Postma MJ, Denig P, Hak E (2014) Efficacy of standard and intensive statin treatment for the secondary prevention of cardiovascular and cerebrovascular events in diabetes patients: a meta-analysis. PLoS One 9:e111247CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Pandit AK, Kumar P, Kumar A, Chakravarty K, Misra S, Prasad K (2016) High-dose statin therapy and risk of intracerebral hemorrhage: a meta-analysis. Acta Neurol Scand 134:22–28CrossRefPubMedGoogle Scholar
  25. 25.
    Brott T, Adams HP Jr, Olinger CP, Walker M (1989) Measurement of acute cerebral infarction: a clinical examination scale. Stroke 20:864–870CrossRefPubMedGoogle Scholar
  26. 26.
    Kang J, Kim N, Park TH, Bang OY, Lee JS, Lee J, Han MK, Park SH, Gorelick PB, Bae HJ (2015) Early statin use in ischemic stroke patients treated with recanalization therapy: retrospective observational study. BMC Neurol 15:122CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Collins R, Armitage J, Parish S, Sleight P, Peto R, Heart Protection Study Collaborative Group (2004) 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 363:757–767CrossRefPubMedGoogle Scholar
  28. 28.
    Cholesterol Treatment Trialists’ (CTT) Collaboration, Baigent C, Blackwell L, Emberson J, Holland LE, Reith C, Bhala N, Peto R, Barnes EH, Keech A, Simes J, Collins R (2010) Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials. Lancet 376: 1670–1681Google Scholar
  29. 29.
    Scheitz JF, MacIsaac RL, Abdul-Rahim AH, Siegerink B, Bath PM, Endres M, Lees KR, Nolte CH, VISTA collaboration (2016) Statins and risk of poststroke hemorrhagic complications. Neurology 86:1590–1596CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    McKinney JS, Kostis WJ (2012) Statin therapy and the risk of intracerebral hemorrhage: a meta-analysis of 31 randomized controlled trials. Stroke 43:2149–2156CrossRefPubMedGoogle Scholar
  31. 31.
    Åsberg S, Eriksson M (2015) Statin therapy and the risk of intracerebral haemorrhage: a nationwide observational study. Int J Stroke Suppl A100:46–49CrossRefGoogle Scholar
  32. 32.
    Fukuma K (2015) Early statin intervention can reduce the early neurological deterioration and recurrence in acute lacunar stroke. Stroke 46:TP65Google Scholar
  33. 33.
    Ueno Y, Yamashiro K, Tanaka Y (2014) Rationale and design of the EPISTEME trial: efficacy of post-stroke intensive rosuvastatin treatment for aortogenic embolic stroke. Cardiovasc Drugs Ther 28:79–85CrossRefPubMedGoogle Scholar
  34. 34.
    Kurzepa J, Bielewicz J, Bartosik-Psujek H, Szczepańska-Szerej A, Stelmasiak Z (2008) Simvastatin inhibits the increase in serum tau protein levels in the acute phase of ischemic stroke. Pharmacol Rep 60:1014–1018PubMedGoogle Scholar

Copyright information

© SIMI 2017

Authors and Affiliations

  • Jing-xue Fang
    • 1
  • Er-qiang Wang
    • 2
  • Wei Wang
    • 1
  • Yang Liu
    • 1
  • Gang Cheng
    • 3
    Email author
  1. 1.School of Life Sciences and BiopharmaceutisShenyang Pharmaceutical UniversityShenyangChina
  2. 2.Department of NeurologyGeneral Hospital of Shenyang Military CommandShenyangChina
  3. 3.School of PharmacyShenyang Pharmaceutical UniversityShenyangChina

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