Association Between Acute Statin Therapy, Survival, and Improved Functional Outcome After Ischemic Stroke: The North Dublin Population Stroke Study

Background and Purpose— Statins improve infarct volume and neurological outcome in animal stroke models. We investigated the relationship between statin therapy and ischemic stroke outcome in the North Dublin Population Stroke Study. Methods— A population-based prospective cohort study was performed using rigorous ascertainment methods. Prestroke and acute (≤72 hours) poststroke medications were recorded. Modified Rankin score and fatality were assessed at 7, 28, and 90 days and 1 year. Results— Of 448 ischemic stroke patients, statins were prescribed before stroke onset in 30.1% (134/445) and were begun acutely (≤72 hours) in an additional 42.5% (189/445). On logistic regression analysis, adjusting for age, prestroke disability (modified Rankin scale), NIHSS score, hypertension, and aspirin, new poststroke statin therapy was independently associated with improved early and late survival (compared with statin untreated patients: OR for death, 0.12; CI, 0.03–0.54 at 7 days; OR, 0.19; CI, 0.07–0.48 at 90 days; OR, 0.26; CI, 0.12–0.55 at 1 year; P≤0.006 for all). Similar findings were observed for statin therapy before stroke onset (adjusted OR for death compared with statin-untreated-patients, 0.04; CI, 0.00–0.33; P=0.003 at 7 days; OR, 0.23; CI, 0.09–0.58; P=0.002 at 90 days; OR, 0.48; CI, 0.23–1.01; P=0.05 at 1 year). Conclusions— Statin therapy at stroke onset and newly begun statins were associated with improved early and late outcomes, supporting data from experimental studies. Randomized trials of statin therapy for treatment of acute stroke are needed.

[1]  M. Reeves.  Letter by Reeves regarding article, "association between acute statin therapy, survival, and improved functional outcome after ischemic stroke: the north dublin population stroke study". , 2011, Stroke.

[2]  K. Furie,et al.  Statin Treatment and Functional Outcome After Ischemic Stroke: Case–Control and Meta-Analysis , 2011, Stroke.

[3]  Gustavo Saposnik,et al.  IScore: A Risk Score to Predict Death Early After Hospitalization for an Acute Ischemic Stroke , 2011, Circulation.

[4]  P. Kelly,et al.  Stroke Subtype Classification to Mechanism-Specific and Undetermined Categories by TOAST, A-S-C-O, and Causative Classification System: Direct Comparison in the North Dublin Population Stroke Study , 2010, Stroke.

[5]  J. Broderick,et al.  Stroke Incidence Is Decreasing in Whites But Not in Blacks: A Population-Based Estimate of Temporal Trends in Stroke Incidence From the Greater Cincinnati/Northern Kentucky Stroke Study , 2010, Stroke.

[6]  M. Hennerici,et al.  Statin Treatment and Stroke Outcome in the Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) Trial , 2009, Stroke.

[7]  Alex J Sutton,et al.  Statins for the prevention and treatment of infections: a systematic review and meta-analysis. , 2009, Archives of internal medicine.

[8]  R. Sacco,et al.  High-Dose Lovastatin for Acute Ischemic Stroke: Results of the Phase I Dose Escalation Neuroprotection with Statin Therapy for Acute Recovery Trial (NeuSTART) , 2009, Cerebrovascular Diseases.

[9]  Robert D. Brown,et al.  Statins in ischemic stroke: just low-density lipoprotein lowering or more? , 2009, Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association.

[10]  S. Schwab,et al.  Neuroprotection by pravastatin in acute ischemic stroke in rats , 2008, Brain Research Reviews.

[11]  J. Gargano,et al.  Effect of Pretreatment With Statins on Ischemic Stroke Outcomes , 2008, Stroke.

[12]  L. Mascitelli,et al.  STATIN TREATMENT WITHDRAWAL IN ISCHEMIC STROKE: A CONTROLLED RANDOMIZED STUDY , 2008, Neurology.

[13]  C. Molina,et al.  Simvastatin in the acute phase of ischemic stroke: a safety and efficacy pilot trial , 2007, European journal of neurology.

[14]  F. F. B. YANIKa,et al.  Hypertriglyceridemia-Induced Acute Pancreatitis During Pregnancy: Editorial Comment , 2018 .

[15]  A. Demchuk,et al.  Fast assessment of stroke and transient ischaemic attack to prevent early recurrence (FASTER): a randomised controlled pilot trial , 2007, The Lancet Neurology.

[16]  M. A. Moro,et al.  Statin treatment withdrawal in ischemic stroke , 2007, Neurology.

[17]  T. Dalkara,et al.  Statin pre-treatment protects brain against focal cerebral ischemia in diabetic mice. , 2007, The Journal of surgical research.

[18]  W. Howard.  Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90 056 participants in 14 randomised trials of statins , 2007 .

[19]  J. Farmer.  High-dose atorvastatin after stroke or transient ischemic attack. , 2007, Current atherosclerosis reports.

[20]  M. Hennerici,et al.  High-dose atorvastatin after stroke or transient ischemic attack. , 2006, The New England journal of medicine.

[21]  R. Califf,et al.  Statin Use and Sex-Specific Stroke Outcomes in Patients With Vascular Disease , 2006, Stroke.

[22]  S. Gutnikov,et al.  Population-based study of event-rate, incidence, case fatality, and mortality for all acute vascular events in all arterial territories (Oxford Vascular Study) , 2005, The Lancet.

[23]  R. Collins,et al.  Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90 056 participants in 14 randomised trials of statins , 2005, The Lancet.

[24]  E. Tremoli,et al.  Neuroprotective effect of simvastatin in stroke: a comparison between adult and neonatal rat models of cerebral ischemia. , 2005, Neurotoxicology.

[25]  R. Sacco,et al.  Lipid-lowering agent use at ischemic stroke onset is associated with decreased mortality , 2005, Neurology.

[26]  K. Lees,et al.  Statin administration prior to ischaemic stroke onset and survival: exploratory evidence from matched treatment–control study , 2005, European journal of neurology.

[27]  M. Fisher,et al.  HMG-CoA Reductase Inhibitors Improve Acute Ischemic Stroke Outcome , 2005, Stroke.

[28]  V. Feigin,et al.  Editorial comment--Stroke incidence studies one step closer to the elusive gold standard? , 2004, Stroke.

[29]  J. Martí-Fàbregas,et al.  Favorable Outcome of Ischemic Stroke in Patients Pretreated with Statins , 2004, Stroke.

[30]  S. Warach,et al.  Rising statin use and effect on ischemic stroke outcome , 2004, BMC medicine.

[31]  Yi Li,et al.  Statins induce angiogenesis, neurogenesis, and synaptogenesis after stroke , 2003, Annals of neurology.

[32]  E. Tremoli,et al.  Treatment With Statins After Induction of Focal Ischemia in Rats Reduces the Extent of Brain Damage , 2003, Arteriosclerosis, thrombosis, and vascular biology.

[33]  K. Hirata,et al.  HMG-CoA Reductase Inhibitor Has Protective Effects Against Stroke Events in Stroke-Prone Spontaneously Hypertensive Rats , 2003, Stroke.

[34]  R. de Caterina,et al.  Statins and stroke: evidence for cholesterol-independent effects , 2002 .

[35]  M. Moskowitz,et al.  Mevastatin, an HMG-CoA reductase inhibitor, reduces stroke damage and upregulates endothelial nitric oxide synthase in mice. , 2001, Stroke.

[36]  B. Psaty,et al.  Assessment and Control for Confounding by Indication in Observational Studies , 1999, Journal of the American Geriatrics Society.

[37]  M. Moskowitz,et al.  Stroke protection by 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase inhibitors mediated by endothelial nitric oxide synthase. , 1998, Proceedings of the National Academy of Sciences of the United States of America.