title: Combining statins with tissue plasminogen activator treatment after experimental and human stroke: a safety study on hemorrhagic transformation.
abstract: OBJECTIVE
  Statins may afford neuroprotection against ischemic injury, but it remains controversial whether combined treatment with tissue plasminogen activator (tPA) after stroke increases the risk of hemorrhagic transformation (HT), the major tPA-related complication. We evaluated the safety of combining statin with tPA administration during the acute phase of both experimental and human stroke.
  
  
  METHODS
  The occurrence and severity of HT, infarct volume, and neurological outcome were evaluated in spontaneous hypertensive rats (SHR) subjected to embolic middle cerebral arterial occlusion (MCAO), which received vehicle or simvastatin (20 mg/kg), 15 min after ischemia and tPA (9 mg/kg) 3 h after ischemia. Additionally, HT rate was evaluated in stroke patients who were treated with tPA (0.9 mg/kg) within 3 h after symptom onset, considering whether or not were under statins treatment when the stroke occurred.
  
  
  RESULTS
  In the experimental study, no differences in HT rates and severity were found between treatment groups, neither regarding mortality, neurological deficit, infarct volume, or metalloproteinases (MMPs) brain content. In the clinical study, HT rates and hemorrhage type were similar in stroke patients who were or not under statins treatment.
  
  
  CONCLUSIONS
  This study consistently confirms that the use of statins does not increase HT rates and severity when is combined with tPA administration.
authors.affiliation: Neurovascular Research Laboratory, Institut de Recerca Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Mireia
authors.initials: M
authors.lastname: Campos
authors.forename: Lidia
authors.initials: L
authors.lastname: García-Bonilla
authors.forename: Mar
authors.initials: M
authors.lastname: Hernández-Guillamon
authors.forename: Verónica
authors.initials: V
authors.lastname: Barceló
authors.forename: Anna
authors.initials: A
authors.lastname: Morancho
authors.forename: Manolo
authors.initials: M
authors.lastname: Quintana
authors.forename: Marta
authors.initials: M
authors.lastname: Rubiera
authors.forename: Anna
authors.initials: A
authors.lastname: Rosell
authors.forename: Joan
authors.initials: J
authors.lastname: Montaner
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D002543:Cerebral Hemorrhage / Q000139:chemically induced / Q000473:pathology*; D015331:Cohort Studies; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011446:Prospective Studies; D011897:Random Allocation; D051381:Rats; D011918:Rats, Inbred SHR; D020521:Stroke / Q000188:drug therapy* / Q000473:pathology*; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D010959:Tissue Plasminogen Activator
keywords: cerebral ischemia; hemorrhagic transformation; spontaneous hypertensive rats; statins; tissue plasminogen activator