본문 바로가기
KERD
논문KCI 등재

Statins in Acute Ischemic Stroke: A Systematic Review

Ji Sung Lee|Keun-Sik Hong
대한뇌졸중학회 (The Korean Stroke Society)|2015.09|대한뇌졸중영문학회지 (Journal of stroke)|제17권 제3호|pp. 282-301

1

조회

0

다운로드

5

인용

0

참고문헌

키워드

MortalityOutcomeAcute ischemic strokeStatinsStroke severitySymptomatic hemorrhagic transformation
주제분류신경과학

초록

Background and Purpose Statins have pleiotropic effects of potential neuroprotection. However, because of lack of large randomized clinical trials, current guidelines do not provide specific recommendations on statin initiation in acute ischemic stroke (AIS). The current study aims to systematically review the statin effect in AIS. Methods From literature review, we identified articles exploring prestroke and immediate post-stroke statin effect on imaging surrogate markers, initial stroke severity, functional outcome, and short-term mortality in human AIS. We summarized descriptive overview. In addition, for subjects with available data from publications, we conducted meta-analysis to provide pooled estimates. Results In total, we identified 70 relevant articles including 6 meta-analyses. Surrogate imaging marker studies suggested that statin might enhance collaterals and reperfusion. Our updated meta-analysis indicated that prestroke statin use was associated with milder initial stroke severity (odds ratio [OR] [95% confidence interval], 1.24 [1.05-1.48]; P=0.013), good functional outcome (1.50 [1.29-1.75]; P<0.001), and lower mortality (0.42 [0.21-0.82]; P=0.0108). In-hospital statin use was associated with good functional outcome (1.31 [1.12-1.53]; P=0.001), and lower mortality (0.41 [0.29-0.58]; P<0.001). In contrast, statin withdrawal was associated with poor functional outcome (1.83 [1.01-3.30]; P=0.045). In patients treated with thrombolysis, statin was associated with good functional outcome (1.44 [1.10-1.89]; P=0.001), despite an increased risk of symptomatic hemorrhagic transformation (1.63 [1.04-2.56]; P=0.035). Conclusions The current study findings support the use of statin in AIS. However, the findings were mostly driven by observational studies at risk of bias, and thereby large randomized clinical trials would provide confirmatory evidence.

Abstract

Background and Purpose Statins have pleiotropic effects of potential neuroprotection. However, because of lack of large randomized clinical trials, current guidelines do not provide specific recommendations on statin initiation in acute ischemic stroke (AIS). The current study aims to systematically review the statin effect in AIS. Methods From literature review, we identified articles exploring prestroke and immediate post-stroke statin effect on imaging surrogate markers, initial stroke severity, functional outcome, and short-term mortality in human AIS. We summarized descriptive overview. In addition, for subjects with available data from publications, we conducted meta-analysis to provide pooled estimates. Results In total, we identified 70 relevant articles including 6 meta-analyses. Surrogate imaging marker studies suggested that statin might enhance collaterals and reperfusion. Our updated meta-analysis indicated that prestroke statin use was associated with milder initial stroke severity (odds ratio [OR] [95% confidence interval], 1.24 [1.05-1.48]; P=0.013), good functional outcome (1.50 [1.29-1.75]; P<0.001), and lower mortality (0.42 [0.21-0.82]; P=0.0108). In-hospital statin use was associated with good functional outcome (1.31 [1.12-1.53]; P=0.001), and lower mortality (0.41 [0.29-0.58]; P<0.001). In contrast, statin withdrawal was associated with poor functional outcome (1.83 [1.01-3.30]; P=0.045). In patients treated with thrombolysis, statin was associated with good functional outcome (1.44 [1.10-1.89]; P=0.001), despite an increased risk of symptomatic hemorrhagic transformation (1.63 [1.04-2.56]; P=0.035). Conclusions The current study findings support the use of statin in AIS. However, the findings were mostly driven by observational studies at risk of bias, and thereby large randomized clinical trials would provide confirmatory evidence.

참고문헌 (93)

  1. Endres M, "Stroke protection by 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase inhibitors mediated by endothelial nitric oxide synthase", Proc Natl Acad Sci U S A, 95, pp.8880~8885 (1998)
  2. Kureishi Y, "The HMG-CoA reductase inhibitor simvastatin activates the protein kinase Akt and promotes angiogenesis in normocholesterolemic animals", Nat Med, 6, pp.1004~1010 (2000)
  3. Laufs U, "Atorvastatin upregulates type III nitric oxide synthase in thrombocytes, decreases platelet activation, and protects from cerebral ischemia in normocholesterolemic mice", Stroke, 31, pp.2442~2449 (2000)
  4. Amin-Hanjani S, "Mevastatin, an HMG-CoA reductase inhibitor, reduces stroke damage and upregulates endothelial nitric oxide synthase in mice", Stroke, 32, pp.980~986 (2001)
  5. Asahi M, "Protective effects of statins involving both eNOS and tPA in focal cerebral ischemia", J Cereb Blood Flow Metab, 25, pp.722~729 (2005)
  6. Goldstein LB, "Statins and ischemic stroke severity: cytoprotection", Curr Atheroscler Rep, 11, pp.296~300 (2009)
  7. Jain MK, "Anti-inflammatory effects of statins : clinical evidence and basic mechanisms", Nat Rev Drug Discov, 4, pp.977~987 (2005)
  8. 문경준, "Antioxidant Effects of Statins in Patients with Atherosclerotic Cerebrovascular Disease", Journal of Clinical Neurology, 10(2), pp.140~147 (2014), 대한신경과학회[DOI]
  9. Chen J, "Statins induce angiogenesis, neurogenesis, and synaptogenesis after stroke", Ann Neurol, 53, pp.743~751 (2003)
  10. Stenestrand U, "Early statin treatment following acute myocardial infarction and 1-year survival", JAMA, 285, pp.430~436 (2001)
  11. Fonarow GC, "Effect of statin use within the first 24 hours of admission for acute myocardial infarction on early morbidity and mortality", Am J Cardiol, 96, pp.611~616 (2005)
  12. Lenderink T, "Patients using statin treatment within 24 h after admission for ST-elevation acute coronary syndromes had lower mortality than non-users : a report from the first Euro Heart Survey on acute coronary syndromes", Eur Heart J, 27, pp.1799~1804 (2006)
  13. Nagashima M, "Effect of early statin treatment at standard doses on long-term clinical outcomes in patients with acute myocardial infarction (the Heart Institute of Japan, Department of Cardiology Statin Evaluation Program)", Am J Cardiol, 99, pp.1523~1528 (2007)
  14. Schwartz GG, "Effects of atorvastatin on early recurrent ischemic events in acute coronary syndromes: the MIRACL study: a randomized controlled trial", JAMA, 285, pp.1711~1718 (2001)
  15. de Lemos JA, "Early intensive vs a delayed conservative simvastatin strategy in patients with acute coronary syndromes: phase Z of the A to Z trial", JAMA, 292, pp.1307~1316 (2004)
  16. Cannon CP, "Intensive versus moderate lipid lowering with statins after acute coronary syndromes", N Engl J Med, 350, pp.1495~1504 (2004)
  17. Winchester DE, "Evidence of pre-procedural statin therapy a meta-analysis of randomized trials", J Am Coll Cardiol, 56, pp.1099~1109 (2010)
  18. O’Gara PT, "2013 ACCF", AHA guideline for the management of ST-elevation myocardial infarction: a report of the American College of Cardiology Foundation, Circulation, pp.2013, 127[DOI]
  19. Anderson JL, "ACCF", AHA focused update incorporated into the ACCF, non-ST-elevation myocardial infarction: a report of the American College of Cardiology Foundation, pp.American Heart Association Task Force on Practice Guidelines, Circulation[DOI]
  20. Levine GN, "2011 ACCF", AHA, American Heart Association Task Force on Practice Guidelines and the Society for Cardiovascular Angiography and Interventions, pp.Circulation, 2011[DOI]
  21. Higgins JPT, "Cochrane Handbook for Systematic Reviews of Interventions" (2008), Cochrane Collaboration and John Wiley & Sons Ltd
  22. Shook SJ, "Statin use is independently associated with smaller infarct volume in nonlacunar MCA territory stroke", J Neuroimaging, 16, pp.341~346 (2006)
  23. Ovbiagele B, "Statin enhancement of collateralization in acute stroke", Neurology, 68, pp.2129~2131 (2007)
  24. Nicholas JS, "The effect of statin pretreatment on infarct volume in ischemic stroke", Neuroepidemiology, 31, pp.48~56 (2008)
  25. Ford AL, "Preexisting statin use is associated with greater reperfusion in hyperacute ischemic stroke", Stroke, 42, pp.1307~1313 (2011)
  26. Sargento-Freitas J, "Preferential effect of premorbid statins on atherothrombotic strokes through collateral circulation enhancement", Eur Neurol, 68, pp.171~176 (2012)
  27. Malik N, "Demographic and clinical predictors of leptomeningeal collaterals in stroke patients", J Stroke Cerebrovasc Dis, 23, pp.2018~2022 (2014)
  28. Lee MJ, "Role of statin in atrial fibrillation-related stroke: an angiographic study for collateral flow", Cerebrovasc Dis, 37, pp.77~84 (2014)
  29. Pourati I, "Statin use is associated with enhanced collateralization of severely diseased coronary arteries", Am Heart J, 146, pp.876~881 (2003)
  30. Jonsson N, "Does pretreatment with statins improve clinical outcome after stroke? A pilot case-referent study", Stroke, 32, pp.1112~1115 (2001)
  31. Marti-Fàbregas J, "Favorable outcome of ischemic stroke in patients pretreated with statins", Stroke, 35, pp.1117~1121 (2004)
  32. Greisenegger S, "Effect of pretreatment with statins on the severity of acute ischemic cerebrovascular events", J Neurol Sci, 221, pp.5~10 (2004)
  33. Yoon SS, "Rising statin use and effect on ischemic stroke outcome", BMC Med, 2, pp.4~ (2004)
  34. Elkind MS, "Lipid-lowering agent use at ischemic stroke onset is associated with decreased mortality", Neurology, 65, pp.253~258 (2005)
  35. Moonis M, "HMG-CoA reductase inhibitors improve acute ischemic stroke outcome", Stroke, 36, pp.1298~1300 (2005)
  36. Aslanyan S, "Statin administration prior to ischaemic stroke onset and survival: exploratory evidence from matched treatment-control study", Eur J Neurol, 12, pp.493~498 (2005)
  37. Bushnell CD, "Statin use and sex-specific stroke outcomes in patients with vascular disease", Stroke, 37, pp.1427~1431 (2006)
  38. Chitravas N, "Is prestroke use of angiotensin-converting enzyme inhibitors associated with better outcome?", Neurology, 68, pp.1687~1693 (2007)
  39. Reeves MJ, "Effect of pretreatment with statins on ischemic stroke outcomes", Stroke, 39, pp.1779~1785 (2008)
  40. Goldstein LB, "Statin treatment and stroke outcome in the Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trial", Stroke, 40, pp.3526~3531 (2009)
  41. Yu AY, "Pre-stroke use of antihypertensives, antiplatelets, or statins and early ischemic stroke outcomes", Cerebrovasc Dis, 27, pp.398~402 (2009)
  42. Martínez-Sánchez P, "The beneficial effect of statins treatment by stroke subtype", Eur J Neurol, 16, pp.127~133 (2009)
  43. Cuadrado-Godia E, "Sex differences in the prognostic value of the lipid profile after the first ischemic stroke", J Neurol, 256, pp.989~995 (2009)
  44. Stead LG, "Statins in ischemic stroke: just low-density lipoprotein lowering or more?", J Stroke Cerebrovasc Dis, 18, pp.124~127 (2009)
  45. Arboix A, "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, pp.47~ (2010)
  46. Sacco S, "Effect of prior medical treatments on ischemic stroke severity and outcome", Funct Neurol, 26, pp.133~139 (2011)
  47. Ní Chróinín D, "Association between acute statin therapy, survival, and improved functional outcome after ischemic stroke: the North Dublin Population Stroke Study", Stroke, 42, pp.1021~1029 (2011)
  48. Tsai NW, "Statin pre-treatment is associated with lower platelet activity and favorable outcome in patients with acute non-cardio-embolic ischemic stroke", Crit Care, 15, pp.R163~ (2011)
  49. Biffi A, "Statin treatment and functional outcome after ischemic stroke: case-control and meta-analysis", Stroke, 42, pp.1314~1319 (2011)
  50. Hassan Y, "Statin use prior to ischemic stroke onset is associated with decreased in-hospital mortality", Fundam Clin Pharmacol, 25, pp.388~394 (2011)
  51. Flint AC, "Inpatient statin use predicts improved ischemic stroke discharge disposition", Neurology, 78, pp.1678~1683 (2012)
  52. Flint AC, "Statin use during ischemic stroke hospitalization is strongly associated with improved poststroke survival", Stroke, 43, pp.147~154 (2012)
  53. Hjalmarsson C, "The effect of statins on acute and long-term outcome after ischemic stroke in the elderly", Am J Geriatr Pharmacother, 10, pp.313~322 (2012)
  54. Aboa-Eboulé C, "Effect of previous statin therapy on severity and outcome in ischemic stroke patients: a population-based study", J Neurol, 260, pp.30~37 (2013)
  55. Phipps MS, "Stroke severity and outcomes for octogenarians receiving statins", Arch Gerontol Geriatr, 57, pp.377~382 (2013)
  56. Martínez-Sánchez P, "Treatment with statins and ischemic stroke severity: does the dose matter?", Neurology, 80, pp.1800~1805 (2013)
  57. Moonis M, "Pre and post-stroke use of statins improves stroke outcome", Indian J Community Med, 39, pp.214~217 (2014)
  58. Cordenier A, "Pre-stroke use of statins on stroke outcome: a meta-analysis of observational studies", Acta Neurol Belg, 111, pp.261~267 (2011)
  59. Ní Chróinín D, "Statin therapy and outcome after ischemic stroke: systematic review and meta-analysis of observational studies and randomized trials", Stroke, 44, pp.448~456 (2013)
  60. Tsai NW, "The association of statin therapy and high-sensitivity C-reactive protein level for predicting clinical outcome in acute non-cardioembolic ischemic stroke", Clin Chim Acta, 413, pp.1861~1865 (2012)
  61. Yeh PS, "Effect of statin treatment on three-month outcomes in patients with stroke-associated infection: a prospective cohort study", Eur J Neurol, 19, pp.689~695 (2012)
  62. Song B, "Association between statin use and short-term outcome based on severity of ischemic stroke: a cohort study", PLoS One, 9, pp.84389~ (2014)
  63. Al-Khaled M, "Statin treatment in patients with acute ischemic stroke", Int J Stroke, 9, pp.597~601 (2014)
  64. Blanco M, "Statin treatment withdrawal in ischemic stroke: a controlled randomized study", Neurology, 69, pp.904~910 (2007)
  65. Alvarez-Sabín J, "Prior statin use may be associated with improved stroke outcome after tissue plasminogen activator", Stroke, 38, pp.1076~1078 (2007)
  66. Bang OY, "Cholesterol level and symptomatic hemorrhagic transformation after ischemic stroke thrombolysis", Neurology, 68, pp.737~742 (2007)
  67. Uyttenboogaart M, "Lipid profile, statin use, and outcome after intravenous thrombolysis for acute ischaemic stroke", J Neurol, 255, pp.875~880 (2008)
  68. Meier N, "Prior statin use, intracranial hemorrhage, and outcome after intra-arterial thrombolysis for acute ischemic stroke", Stroke, 40, pp.1729~1737 (2009)
  69. Restrepo L, "Impact of hyperlipidemia and statins on ischemic stroke outcomes after intra-arterial fibrinolysis and percutaneous mechanical embolectomy", Cerebrovasc Dis, 28, pp.384~390 (2009)
  70. Miedema I, "Statin use and functional outcome after tissue plasminogen activator treatment in acute ischaemic stroke", Cerebrovasc Dis, 29, pp.263~267 (2010)
  71. Engelter ST, "IV thrombolysis and statins", Neurology, 77, pp.888~895 (2011)
  72. Cappellari M, "Does statin in the acute phase of ischemic stroke improve outcome after intravenous thrombolysis? A retrospective study", J Neurol Sci, 308, pp.128~134 (2011)
  73. Meseguer E, "Outcomes after thrombolysis in AIS according to prior statin use: a registry and review", Neurology, 79, pp.1817~1823 (2012)
  74. Rocco A, "Impact of statin use and lipid profile on symptomatic intracerebral haemorrhage, outcome and mortality after intravenous thrombolysis in acute stroke", Cerebrovasc Dis, 33, pp.362~368 (2012)
  75. Martinez-Ramirez S, "Statin pretreatment may increase the risk of symptomatic intracranial haemorrhage in thrombolysis for ischemic stroke: results from a case-control study and a meta-analysis", J Neurol, 259, pp.111~118 (2012)
  76. Cappellari M, "The THRombolysis and STatins (THRaST) study", Neurology, 80, pp.655~661 (2013)
  77. Zhao HD, "The effects of previous statin treatment on plasma matrix metalloproteinase-9 level in chinese stroke patients undergoing thrombolysis", J Stroke Cerebrovasc Dis, 23, pp.2788~2793 (2014)
  78. Scheitz JF, "Dose-related effects of statins on symptomatic intracerebral hemorrhage and outcome after thrombolysis for ischemic stroke", Stroke, 45, pp.509~514 (2014)
  79. Scheitz JF, "Reduced risk of poststroke pneumonia in thrombolyzed stroke patients with continued statin treatment", Int J Stroke, 10, pp.61~66 (2015)
  80. Rodríguez de Antonio LA, "Previous statins treatment and risk of post-stroke infections", Neurologia, 26, pp.150~156 (2011)
  81. Rodríguez-Sanz A, "High-density lipoprotein: a novel marker for risk of in-hospital infection in acute ischemic stroke patients?", Cerebrovasc Dis, 35, pp.291~297 (2013)
  82. Becker K, "Early statin use is associated with increased risk of infection after stroke", J Stroke Cerebrovasc Dis, 22, pp.66~71 (2013)
  83. Kennedy J, "Fast assessment of stroke and transient ischaemic attack to prevent early recurrence (FASTER): a randomised controlled pilot trial", Lancet Neurol, 6, pp.961~969 (2007)
  84. Montaner J, "Simvastatin in the acute phase of ischemic stroke: a safety and efficacy pilot trial", Eur J Neurol, 15, pp.82~90 (2008)
  85. Muscari A, "The atorvastatin during ischemic stroke study: a pilot randomized controlled trial", Clin Neuropharmacol, 34, pp.141~147 (2011)
  86. Beer C, "A randomized placebo controlled trial of early treatment of acute ischemic stroke with atorvastatin and irbesartan", Int J Stroke, 7, pp.104~111 (2012)
  87. Zare M, "The effect of statin therapy in stroke outcome: a double blind clinical trial", Int J Prev Med, 3, pp.68~72 (2012)
  88. Squizzato A, "Statins for acute ischemic stroke", Cochrane Database Syst Rev, (8), pp.CD007551~ (2011)
  89. Elkind MS, "High-dose lovastatin for acute ischemic stroke: results of the phase I dose escalation neuroprotection with statin therapy for acute recovery trial (NeuSTART)", Cerebrovasc Dis, 28, pp.266~275 (2009)
  90. Jauch EC, "Guidelines for the early management of patients with acute ischemic stroke: a guideline for healthcare professionals from the American Heart Association", American Stroke Association, 2013, pp.44, 870~947
  91. Choi JC, "Effect of pre-stroke statin use on stroke severity and early functional recovery: a retrospective cohort study", BMC Neurol, 15, pp.120~ (2015)
  92. Bavry AA, "Long-term benefit of statin therapy initiated during hospitalization for an acute coronary syndrome: a systematic review of randomized trials", Am J Cardiovasc Drugs, 7, pp.135~141 (2007)
  93. Afilalo J, "Intensive statin therapy in acute coronary syndromes and stable coronary heart disease: a comparative meta-analysis of randomised controlled trials", Heart, 93, pp.914~921 (2007)

관련 논문AI추천

Effect and Safety of Rosuvastatin in Acute Ischemic Stroke김영대, 김윤남, 김응엽, 남효석, 송동범, 유준상, 윤병우, 이경열, 이기정, 이병철, 허지회, Jong S. Kim대한뇌졸중학회 · 대한뇌졸중영문학회지2016 · 제18권 제1호Early Statins after Intravenous or Endovascular Recanalization Is Beneficial Regardless of Timing, Intensity, and Stroke Mechanism김범준, 배희준, 양미화, 정한길, 한문구대한뇌졸중학회 · 대한뇌졸중영문학회지2017 · 제19권 제3호급성기 뇌경색 환자에서 Staitn 처방과 임상결과 지표 분석구희원, 김귀숙, 서성연, 이주연, 정근화, 조윤숙한국병원약사회 · 병원약사회지2018 · 제35권 제2호Statin Prescription Adhered to Guidelines for Patients Hospitalized due to Acute Ischemic Stroke or Transient Ischemic Attack권형민, 배희준, 오미선, 유경호, 이병철, 이준영, 조아현, 최혜연, 홍근식대한신경과학회 · Journal of Clinical Neurology2013 · 제9권 제4호Dyslipidemia Treatment and Cerebrovascular Disease: Evidence Regarding the Mechanism of Stroke김범준, Ha Sang Hee한국지질동맥경화학회 · 지질·동맥경화학회지2024 · 제13권 제2호Endovascular Recanalization Therapy in Acute Ischemic Stroke: Updated Meta-analysis of Randomized Controlled Trials고상배, 나정호, 유경호, 이지성, 홍근식대한뇌졸중학회 · 대한뇌졸중영문학회지2015 · 제17권 제3호

이 간행물의 다른 논문 (16건)

Choosing a Hyperacute Stroke Imaging Protocol for Proper Patient Selection and Time Efficient Endovascular Treatment: Lessons from Recent TrialsAndrew M. Demchuk, Jin Soo Leepp. 221-228Patent Foramen Ovale and Stroke–Current StatusOh Young Bang, Mi ji Lee, Sookyung Ryoo, Suk Jae Kim, Ji Won Kimpp. 229-237Vessel Wall Imaging of the Intracranial and Cervical Carotid ArteriesDeok Hee Lee, Young Jun Choi, Seung Chai Jungpp. 238-255Stroke Connectome and Its Implications for Cognitive and Behavioral Sequela of StrokeJae-Sung Lim, Dong-Wha Kangpp. 256-267Endovascular Recanalization Therapy in Acute Ischemic Stroke: Updated Meta-analysis of Randomized Controlled Trials홍근식, 나정호, 고상배, 유경호, 이지성pp. 268-281
원문 보기