Direct Endovascular Thrombectomy or With Prior Intravenous Thrombolysis for Acute Ischemic Stroke: A Meta-Analysis

Abstract

Background and purpose: It is unclear whether endovascular thrombectomy alone compared with intravenous thrombolysis combination with endovascular thrombectomy can achieve similar neurological outcomes in patients with acute large vessel occlusion stroke. We aimed to perform a systematic review and meta-analysis of randomized controlled trials to compare endovascular thrombectomy alone or intravenous thrombolysis plus endovascular thrombectomy in this population.Methods: We systematically searched PubMed, Embase, and ClinicalTrials.gov. We restricted our search to randomized clinical trials that examined the clinical outcomes of endovascular thrombectomy alone vs. intravenous thrombolysis plus endovascular thrombectomy. The Cochrane risk of bias tool was used to assess study quality. Random-effects meta-analyses were used for evaluating all outcomes.Results: Total three randomized controlled trials with 1,092 individuals enrolled were included in the meta-analysis, including 543 (49.7%) who received endovascular thrombectomy alone and 549 (50.3%) who received intravenous thrombolysis plus endovascular thrombectomy. The primary outcome of 90-day functional independence (modified Rankin scale (mRS) score ≤ 2) was 44.6% (242/543) in the endovascular thrombectomy alone group vs. 42.8% (235/549) in the alteplase with endovascular thrombectomy group (odds ratio (OR), 1.08 [95% CI, 0.85–1.38]; P = 0.0539). Among pre-specified secondary outcomes, no significant between-group differences were found in excellent outcome (mRS score ≤ 1) (OR, 1.12 [95% CI, 0.85–1.47]; P = 0.418), mortality at 90 days (OR, 0.93 [95% CI, 0.68–1.29]; P = 0.673), successful reperfusion (thrombolysis in cerebral infarction 2b-3) (OR, 0.75 [95% CI, 0.54–1.05]; P = 0.099), and symptomatic intracranial hemorrhage (OR, 0.72 [95% CI, 0.45–1.15]; P = 0.171).Conclusions: Among patients with acute ischemic stroke in the anterior circulation within 4.5 h from the onset, endovascular thrombectomy alone was non-inferior to combined intravenous thrombolysis and endovascular thrombectomy.

Endovascular thrombectomy with or without intravenous alteplase for acute ischemic stroke due to large vessel occlusion: a systematic review and meta-analysis of randomized trials

“…Compared with two recent published systematic reviews addressing EVT alone versus EVT with intravenous thrombolysis in acute ischaemic stroke from large vessel occlusion,34 35 our review had the following distinctions. First, we used the GRADE approach to evaluate the certainty of evidence, which formally acknowledges imprecision in effect estimates.…”

“…In the systematic review of four trials, surrogate endpoints (successful reperfusion and any intracranial haemorrhage) showed significant improvement, the first favouring EVT plus alteplase and the second favouring EVT alone, and the authors did not address this issue 34. In the systematic review of three trials, there were no significant differences in successful reperfusion 35. Surrogate outcomes are less important when we have evidence to directly inform patient-important outcomes 36.…”

“…Our review recognised this and hence did not report these surrogate outcomes. Finally, on the definition of sICH used in these RCTs,13–18 we chose the Heidelberg criteria for DIRECT-MT, DEVT and MR CLEAN-NO IV trials,13 15 16 and the Safe Implementation of Thrombolysis in Stroke–Monitoring Study (SITS–MOST) criteria for the SKIP trial,14 while for the SWIFT DIRECT and DIRECT SAFE17 18 trials we used their own trial-specific definitions (online supplemental appendices 2 and 6); the previous systematic review of four trials34 used Heidelberg criteria for DIRECT-MT and MR CLEAN-NO IV trials13 16 and National Institute of Neurological Disorders and Stroke (NINDS) criteria for SKIP and DEVT trials14 15 (online supplemental appendix 6); the previous systematic review of three trials35 used Heidelberg criteria for DIRECT-MT trials13 and NINDS criteria for SKIP and DEVT trials 14 15. Notwithstanding these differences in methods, our conclusion is essentially the same—there is little to no differences in outcomes with EVT alone compared with EVT plus alteplase.…”

Clinical evidence comparing bridging and direct endovascular thrombectomy: progress and controversies

“…The PRISMA flow diagram of search strategy and the process of screening and study selection are shown in figure 1. Twenty-five relevant studies were finally included in qualitative synthesis 15–20 24–42…”

“…Several RCTs (eg, DIRECT-MT, DEVT, SKIP, MR CLEAN-NO IV, SWIFT DIRECT, and DIRECT-SAFE) and observational studies have been performed, greatly updating the clinical evidence available to clinicians 9–14. Subsequently, meta-analyses have attempted to further clarify this issue 15–20. However, these attempts and their source data differ in their methodologies and data reporting systems, limiting the ability to accurately assimilate data from different studies.…”