Abstract DP178: Adjunctive Intra-arterial Thrombolysis after Thrombectomy in Large Vessel Occlusion – A Network Meta-Analysis of Randomized Controlled Trials Evaluating Agents and Dosages

Background: Patients with successfully recanalized large vessel occlusions by endovascular thrombectomy (EVT) may have better functional outcomes after treatment with intra-arterial thrombolytic drugs (IAT). However, the relative efficacy and safety of different IAT agents and their respective doses remain unclear. Methods: We conducted a network meta-analysis of seven randomized clinical trials (RCTs) evaluating the effects of various doses of adjunctive IA thrombolytic agents compared to controls after successful thrombectomy. The primary efficacy outcome was excellent functional recovery at 90 days, defined as a modified Rankin Scale (mRS) score of 0-1. The primary safety outcome was symptomatic intracranial hemorrhage (sICH). Between-group comparison was estimated using odds ratios with 95% credible intervals. Treatment rankings among all compared interventions were assessed using surface under the cumulative ranking curve (SUCRA) probabilities. Results: In total, we analyzed 2,193 patients across six treatment nodes: tenecteplase (0.03125 mg/kg, 0.0625 mg/kg, 0.125 mg/kg), alteplase (0.225 mg/kg), Urokinase (100,000 IU) and controls (no IA thrombolytic drug). The network diagram is shown in Fig 1. Two treatments were associated with higher odds of excellent functional outcome as compared to controls: IA alteplase at 0.225 mg/kg (OR 2.03, 95%CrI 1.37 – 3.03, Fig 2B) and IA tenecteplase at 0.125 mg/kg (OR 1.91, 95% CrI 1.13-3.28, Figure 2B). However, IA alteplase and tenecteplase at 0.125 mg/kg did not outperform other IA agents (Fig 2). SUCRA plots suggested that there is a 52.38% chance that IA alteplase is the most effective treatment, and a 39.97% chance that TNK 0.125mg/kg is the most effective (Figure 3). IA tenecteplase at 0.03125 and 0.0625 mg/kg, along with urokinase, did not show a significant benefit over the control group for excellent functional outcomes (Fig 2). For safety, no IAT agent significantly reduced or increased the risk of sICH. Conclusion: Intra-arterial alteplase 0.225mg/kg and tenecteplase 0.125 mg/kg appear most likely to improve functional recovery following successful EVT compared to controls, though our results are limited by small sample sizes in certain treatment nodes, and dichotomization of outcomes which lack granularity. Further head-to-head trials are needed.