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. Intraarterial 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.