Intra-Arterial Thrombolysis vs. Standard Treatment or Intravenous Thrombolysis in Adults with Acute Ischemic Stroke: A Systematic Review and Meta-Analysis

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.