title: Intra-arterial thrombolysis vs. standard treatment or intravenous thrombolysis in adults with acute ischemic stroke: a systematic review and meta-analysis.
abstract: BACKGROUND
  Recent evidence has suggested that intra-arterial thrombolysis may provide benefit beyond intravenous thrombolysis in ischemic stroke patients. Previous meta-analyses have only compared intra-arterial thrombolysis with standard treatment without thrombolysis. The objective was to review the benefits and harms of intra-arterial thrombolysis in ischemic stroke patients.
  
  
  METHODS
  We undertook a meta-analysis of randomized controlled trials comparing the efficacy and safety of intra-arterial thrombolysis with either standard treatment or intravenous thrombolysis following acute ischemic stroke. Primary outcomes included poor functional outcomes (modified Rankin Scale 3-6), mortality, and symptomatic intracranial hemorrhage. Study quality was assessed, and outcomes were stratified by comparison treatment received.
  
  
  RESULTS
  Four trials (n = 351) comparing intra-arterial thrombolysis with standard treatment were identified. Intra-arterial thrombolysis reduced the risk of poor functional outcomes (modified Rankin Scale 3-6) [relative risk (RR) = 0·80; 95% confidence interval = 0·67-0·95; P = 0·01]. Mortality was not increased (RR = 0·82; 95% confidence interval = 0·56-1·21; P = 0·32); however, risk of symptomatic intracranial hemorrhage was nearly four times more likely (RR = 3·90; 95% confidence interval = 1·41-10·76; P = 0·006). Two trials (n = 81) comparing intra-arterial thrombolysis with intravenous thrombolysis were identified. Intra-arterial thrombolysis was not found to reduce poor functional outcomes (modified Rankin Scale 3-6) (RR = 0·68; 95% confidence interval = 0·46-1·00; P = 0·05). Mortality was not increased (RR = 1·12; 95% confidence interval = 0·47-2·68; P = 0·79); neither was symptomatic intracranial hemorrhage (RR = 1·13; 95% confidence interval = 0·32-3·99; P = 0·85). Differences in time from symptom onset-to-treatment and type of thrombolytic administered were found across the trials.
  
  
  CONCLUSIONS
  This analysis finds a modest benefit of intra-arterial thrombolysis over standard treatment, although it does not find a clear benefit of intra-arterial thrombolysis over intravenous thrombolysis in acute ischemic stroke patients. However, few trials, small sample sizes, and indirectness limit the strength of evidence.
authors.affiliation: Department of Clinical Epidemiology and Biostatistics, Programs for Assessment of Technology in Health (PATH) Research Institute, St. Joseph's Healthcare, McMaster University, Hamilton, ON, Canada.
authors.forename: Julian
authors.initials: J
authors.lastname: Nam
authors.forename: He
authors.initials: H
authors.lastname: Jing
authors.forename: Daria
authors.initials: D
authors.lastname: O'Reilly
mesh_terms: D005343:Fibrinolytic Agents / Q000008:administration & dosage*; D006801:Humans; D007261:Infusions, Intra-Arterial; D007262:Infusions, Intravenous; D016032:Randomized Controlled Trials as Topic; D020127:Recovery of Function / Q000187:drug effects; D020521:Stroke / Q000188:drug therapy*; D015912:Thrombolytic Therapy / Q000379:methods*
chemical_list: D005343:Fibrinolytic Agents
keywords: intra-arterial thrombolysis; intravenous thrombolysis; ischemic stroke; late-presentation; meta-analysis; systematic review