title: Dose-related effects of statins on symptomatic intracerebral hemorrhage and outcome after thrombolysis for ischemic stroke.
abstract: OBJECTIVE
  The aim of our study was to assess whether statins have dose-dependent effects on risk of symptomatic intracerebral hemorrhage (sICH) and outcome after intravenous thrombolysis for ischemic stroke.
  
  
  METHODS
  We pooled data from 2 European intravenous thrombolysis registries. Statin doses were stratified in 3 groups according to the attainable lowering of cholesterol levels (low dose: simvastatin 20 mg or equivalent; medium dose: simvastatin 40 mg or equivalent; and high dose: simvastatin 80 mg or equivalent). sICH was defined according to the European Cooperative Acute Stroke Study. Modified Rankin Scale score 0 to 2 at 3 months was considered a favorable outcome.
  
  
  RESULTS
  Among 1446 patients analyzed (median age, 75 years; median initial National Institutes of Health Stroke Scale score, 11; 54% men), 317 (22%) used statins before intravenous thrombolysis. Of them, 120 patients had low-dose, 134 medium-dose, and 63 high-dose statin therapy. sICH occurred in 4% of patients (n=53). Frequency of sICH was 2%, 6%, and 13% in patients with low-, medium-, and high-dose statin treatment, respectively (P<0.01). Adjusted odds ratio (OR) for sICH was 2.4 (95% confidence interval [CI], 1.1-5.3) and 5.3 (95% CI, 2.3-12.3) for patients with medium- and high-dose statins compared with non-statin users. Statin users more often achieved favorable outcome compared with non-statin users (58% versus 51%; P=0.03). An independent association of statin use with favorable outcome was detected (adjusted OR, 1.8; 95% CI, 1.3-2.5). The association was maintained when stratifying for statin dose, although it was not significant in the high-dose group anymore (OR, 1.7; 95% CI, 0.9-3.2).
  
  
  CONCLUSIONS
  We observed an association between increasing dose of statin use and risk of sICH after intravenous thrombolysis. Nevertheless, there was an overall beneficial effect of previous statin use on favorable 3-month outcome.
authors.affiliation: From Klinik und Hochschulambulanz für Neurologie (J.F.S., S.T., H.J.A., M.E., C.H.N.), Center for Stroke Research (J.F.S., H.J.A., J.B.F., M.E., C.H.N.), and Excellence Cluster NeuroCure (M.E.), Charité-Universitätsmedizin Berlin, Germany; and Department of Neurology and Stroke Unit, University Hospital Basel, Basel, Switzerland (D.J.S., H.G., L.H.B., C.T., P.A.L., S.T.E.).
authors.forename: Jan F
authors.initials: JF
authors.lastname: Scheitz
authors.forename: David J
authors.initials: DJ
authors.lastname: Seiffge
authors.forename: Serdar
authors.initials: S
authors.lastname: Tütüncü
authors.forename: Henrik
authors.initials: H
authors.lastname: Gensicke
authors.forename: Heinrich J
authors.initials: HJ
authors.lastname: Audebert
authors.forename: Leo H
authors.initials: LH
authors.lastname: Bonati
authors.forename: Jochen B
authors.initials: JB
authors.lastname: Fiebach
authors.forename: Christopher
authors.initials: C
authors.lastname: Tränka
authors.forename: Philippe A
authors.initials: PA
authors.lastname: Lyrer
authors.forename: Matthias
authors.initials: M
authors.lastname: Endres
authors.forename: Stefan T
authors.initials: ST
authors.lastname: Engelter
authors.forename: Christian H
authors.initials: CH
authors.lastname: Nolte
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002545:Brain Ischemia / Q000150:complications* / Q000628:therapy*; D002543:Cerebral Hemorrhage / Q000517:prevention & control*; D008078:Cholesterol, LDL / Q000097:blood; D015331:Cohort Studies; D003627:Data Interpretation, Statistical; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D012042:Registries; D012044:Regression Analysis; D020521:Stroke / Q000150:complications* / Q000628:therapy*; D015912:Thrombolytic Therapy / Q000009:adverse effects*; D016896:Treatment Outcome
chemical_list: D008078:Cholesterol, LDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors
keywords: hemorrhage; hydroxymethylglutaryl-CoA reductase inhibitors; stroke; thrombolytic therapy; tissue plasminogen activator