title: Intravenous thrombolysis for acute ischemic stroke associated to extracranial internal carotid artery occlusion: the ICARO-2 study.
abstract: OBJECTIVE
  In a case-control study in patients with acute ischemic stroke and extracranial internal carotid artery (eICA) occlusion, thrombolytic treatment was associated with increased mortality. The aim of this cohort study was to assess the efficacy and safety of thrombolysis in patients with eICA occlusion compared to those without eICA occlusion.
  
  
  METHODS
  Consecutive patients treated with intravenous tissue-type plasminogen activator within 4.5 h from symptom onset included in the Safe Implementation of Thrombolysis in Stroke - International Stroke Thrombolysis Registry (SITS-ISTR) in 20 Italian centres were analyzed. Acute carotid occlusion was diagnosed using ultrasound examination, angio-CT scan or angio-MRI. Since the SITS-ISTR database did not plan to report the site of vessel occlusion, each participating center provided the code of the patient with eICA occlusion. Patients were divided into 2 groups, those with and those without eICA occlusion. Main outcome measures were: death, disability (modified Rankin Scale, mRS, 3-6) and any intracranial bleeding at 3 months. Multiple logistic regression analysis was performed to reveal predictors for main outcomes. The following variables of interest were included in the analysis: presence of eICA occlusion, age, gender, diabetes mellitus, hyperlipidemia, atrial fibrillation, congestive heart failure, previous stroke, current smoking, antiplatelet treatment at stroke onset, baseline NIHSS score, baseline blood glucose, cholesterol and blood pressure, history of hypertension and stroke onset to treatment time.
  
  
  RESULTS
  A total of 1,761 patients without eICA occlusion and 137 with eICA occlusion were included in the study. At 3 months, 42 patients were lost to follow-up (3 with eICA occlusion). Death occurred in 30 (22.4%) patients with eICA occlusion and in 175 (10.2%) patients without (p < 0.0001). Death or disability at 3 months occurred in 91 of 134 patients with eICA occlusion (67.9%) compared with 654 of 1,722 patients without eICA occlusion (37.9%, p < 0.0001). No or minimal disability at 3 months (mRS 0-1) was reported in 25 (18.7%) patients with eICA occlusion and in 829 (48.2%) patients without (p < 0.0001). Any intracranial bleeding detected by CT or MRI at posttreatment imaging was seen in 16 (11.7%) patients with eICA occlusion and in 314 (17.8%) of those without (p = 0.09). The proportion of symptomatic intracerebral hemorrhage was 5.8% for patients with eICA occlusion and 8.0% for patients without (p = 0.16). At logistic regression analysis, eICA occlusion was associated with mortality (odds ratio, OR 5.7; 95% confidence interval, CI 2.9-11.1) and mortality or disability (OR 5.0; 95% CI 2.9-8.7) at 90 days.
  
  
  CONCLUSIONS
  This cohort study in patients with acute ischemic stroke treated with thrombolysis showed an association between eICA occlusion and adverse outcome.
authors.affiliation: Stroke Unit and Division of Cardiovascular Medicine, University of Perugia, Perugia, Italy. mpaciaroni@med.unipg.it
authors.forename: Maurizio
authors.initials: M
authors.lastname: Paciaroni
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Agnelli
authors.forename: Valeria
authors.initials: V
authors.lastname: Caso
authors.forename: Alessio
authors.initials: A
authors.lastname: Pieroni
authors.forename: Paolo
authors.initials: P
authors.lastname: Bovi
authors.forename: Manuel
authors.initials: M
authors.lastname: Cappellari
authors.forename: Andrea
authors.initials: A
authors.lastname: Zini
authors.forename: Paolo
authors.initials: P
authors.lastname: Nichelli
authors.forename: Domenico
authors.initials: D
authors.lastname: Inzitari
authors.forename: Mascia
authors.initials: M
authors.lastname: Nesi
authors.forename: Patrizia
authors.initials: P
authors.lastname: Nencini
authors.forename: Alessandro
authors.initials: A
authors.lastname: Pezzini
authors.forename: Alessandro
authors.initials: A
authors.lastname: Padovani
authors.forename: Tiziana
authors.initials: T
authors.lastname: Tassinari
authors.forename: Giovanni
authors.initials: G
authors.lastname: Orlandi
authors.forename: Alberto
authors.initials: A
authors.lastname: Chiti
authors.forename: Gino
authors.initials: G
authors.lastname: Gialdini
authors.forename: Andrea
authors.initials: A
authors.lastname: Alberti
authors.forename: Michele
authors.initials: M
authors.lastname: Venti
authors.forename: Monica
authors.initials: M
authors.lastname: Acciarresi
authors.forename: Cataldo
authors.initials: C
authors.lastname: D'Amore
authors.forename: Emilio
authors.initials: E
authors.lastname: Luda
authors.forename: Rossana
authors.initials: R
authors.lastname: Tassi
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Martini
authors.forename: Carlo
authors.initials: C
authors.lastname: Ferrarese
authors.forename: Simone
authors.initials: S
authors.lastname: Beretta
authors.forename: Claudia
authors.initials: C
authors.lastname: Trentini
authors.forename: Giorgio
authors.initials: G
authors.lastname: Silvestrelli
authors.forename: Alessia
authors.initials: A
authors.lastname: Lanari
authors.forename: Paolo
authors.initials: P
authors.lastname: Previdi
authors.forename: Alfonso
authors.initials: A
authors.lastname: Ciccone
authors.forename: Maria Luisa
authors.initials: ML
authors.lastname: Delodovici
authors.forename: Giorgio
authors.initials: G
authors.lastname: Bono
authors.forename: Giampiero
authors.initials: G
authors.lastname: Galletti
authors.forename: Simona
authors.initials: S
authors.lastname: Marcheselli
authors.forename: Massimo
authors.initials: M
authors.lastname: Del Sette
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Traverso
authors.forename: Maurizio
authors.initials: M
authors.lastname: Riva
authors.forename: Mauro
authors.initials: M
authors.lastname: Silvestrini
authors.forename: Raffaella
authors.initials: R
authors.lastname: Cerqua
authors.forename: Domenico
authors.initials: D
authors.lastname: Consoli
authors.forename: Serena
authors.initials: S
authors.lastname: Monaco
authors.forename: Danilo
authors.initials: D
authors.lastname: Toni
mesh_terms: D061605:Administration, Intravenous; D000368:Aged; D000369:Aged, 80 and over; D002545:Brain Ischemia / Q000188:drug therapy / Q000401:mortality; D002340:Carotid Artery Diseases / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D005343:Fibrinolytic Agents / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D015337:Multicenter Studies as Topic; D017063:Outcome Assessment, Health Care / Q000379:methods; D020521:Stroke / Q000150:complications / Q000188:drug therapy*; D015912:Thrombolytic Therapy / Q000009:adverse effects; D010959:Tissue Plasminogen Activator / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D005343:Fibrinolytic Agents; D010959:Tissue Plasminogen Activator