Endovascular thrombectomy with or without intravenous thrombolysis in large-vessel ischemic stroke: A non-inferiority meta-analysis of 6 randomised controlled trials

Background: It is unclear whether thrombectomy alone is non-inferior to thrombectomy with intravenous thrombolysis in patients with acute ischemic stroke due to large-vessel occlusion.Purpose: To perform a comprehensive, trial-level data, non-inferiority meta-analysis of randomised controlled trials comparing endovascular thrombectomy with and without intravenous thrombolysis in patients with ischemic stroke due to large-vessel occlusion of anterior circulation.Methods: The prespecified primary efficacy outcome was functional independence, defined as a modified Rankin scale (mRS)score of 0 to 2 at 90 days. The two prespecified non-inferiority margins were risk differences of-10% and -5%. The study was registered in PROSPERO (CRD42022361110) and conducted according to PRISMA guidelines.Results: Six trials were included in this analysis (DIRECT-MT, DEVT, SKIP, MR CLEAN-NO IV, DIRECT-SAFE and SWIFT DIRECT) comprising a total of 2334 patients. Functional independence at 90 days was achieved by 570 (49.0%) of 1164 patients in the thrombectomy alone group and 595 (50.9%) of 1170 patients in the throm-bectomy with thrombolysis group (pooled risk difference -0.02, [95% CI-0.06-0.02]). Combined thrombec-tomy and thrombolysis were associated with significantly higher rates of successful reperfusion (pooled risk ratio 0.96 [95% CI, 0.93-0.99], p = 0.006) but at the expense of a significantly increased risk of overall -but not symptomatic -intracranial haemorrhage (pooled risk ratio 0.87 [95% CI, 0.77-0.98], p = 0.02).Conclusions: Compared with a combined treatment approach, thrombectomy alone was non-inferior at-10% non-inferiority margin, but not at a -5% inferiority margin for functional independence. Current evidence cannot exclude clinically important differences between the two treatment approaches.

Automated summary

This study compared the efficacy between thrombectomy alone and thrombectomy with intravenous thrombolysis in patients with acute ischemic stroke due to large-vessel occlusion. The results showed that although combined treatment increased successful reperfusion, it also increased the risk of overall intracranial hemorrhage. Thrombectomy alone was non-inferior to combined treatment in terms of functional independence at a 10% non-inferiority margin, but not at a 5% inferiority margin.