E-024 Meta-analysis of randomized intra-arterial thrombolytic trials in the treatment of acute stroke. (16th November 2010) - Fields, J
Abstract : Background: Intra-arterial (IA) administration of tissue plasminogen activator (tPA) is an important therapeutic modality in the treatment of acute stroke. Three randomized, multicenter, placebo controlled trials have been performed evaluating IA thrombolytics within 6 h of onset of acute ischemic stroke; two of the trials were positive on some but not all functional end points and a third trial showed non-significant trends on all outcomes. We performed a meta-analysis to estimate with more precision the effect of IA tPA on several key clinical end points. Methods: We evaluated the PROACT, PROACT II and MELT trial methodologies to assess for compatibility in study protocols and statistical analysis. Data were then abstracted from these three trials and statistical analysis was performed using RevMan (RevMan V.5.0, The Nordic Cochrane Centre, Cochrane Collaboration, 2008). The following end points were evaluated: modified Rankin Scale (mRS) ≤1; mRS≤2; National Institutes of Health Stroke Scale (NIHSS) score 0 or 1; 90 day mortality; and spontaneous intracerebral hemorrhage (SICH) within 24 h. Results: Despite minor differences in protocols, the three trials appeared suitable for combined analysis. Functional outcomes were significantly improved by IA thrombolytic administration: IA thrombolytic treated patients were significantly more likely to have a mRS ≤1 (OR 2.0, 95% CI 1.1 to 3.6); mRS ≤2 (OR 1.7, 95% CI 1.0 to 2.9); and NIHSS score 0 or 1 (OR 2.4, 95% CI 1.3 to 4.4) at 90 day follow-up. There was no effect on mortality at 90 day (OR 0.84, 95% CI 0.5 to 1.5). The risk of SICH was significantly increased in the active treatment arms (OR 4.6, 95% CI 1.3 to 16). Conclusions: Meta-analysis of the randomized trials assessing IA administration of thrombolytics demonstrates that all standard functional end points for stroke trials were substantially improved in the active treatment arms. Despite a significantly increased risk of intracerebral hemorrhage, there was no net effect on mortality. These results support endovascular treatment of acute ischemic stroke patients with intra-arterial lytics.