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.