Siddhart Mehta

Systematic Review and Pooled Analyses of Recent Neurointerventional Randomized Controlled Trials: Setting a New Standard of Care for Acute Ischemic Stroke Treatment after 20 Years.

Background: Recent advances in the treatment of ischemic stroke have focused on revascularization and led to better clinical and functional outcomes. A systematic review and pooled analyses of 6 recent multicentered prospective randomized controlled trials (MPRCT) were performed to compare intravenous tissue plasminogen activator (IV tPA) and endovascular therapy (intervention) with IV tPA alone (control) for anterior circulation ischemic stroke (AIS) secondary to large vessel occlusion (LVO). Objectives: Six MPRCTs (MR CLEAN, ESCAPE, EXTEND IA, SWIFT PRIME, REVASCAT and THERAPY) incorporating image-based LVO AIS were selected for assessing the following: (1) prespecified primary clinical outcomes of AIS patients in intervention and control arms: good outcomes were defined by a modified Rankin Scale score of 0-2 at 90 days; (2) secondary clinical outcomes were: (a) revascularization rates [favorable outcomes defined as modified Thrombolysis in Cerebral Infarction scale (mTICI) score of 2b/3]; (b) symptomatic intracranial hemorrhage (sICH) rates and mortality; (c) derivation of number needed to harm (NNH), number needed to treat (NNT), and relative percent difference (RPD) between intervention and control groups, and (d) random effects model to determine overall significance (forest and funnel plots). Results: A total of 1,386 patients were included. Good outcomes at 90 days were seen in 46% of patients in the intervention (p < 0.00001) and in 27% of patients in the control groups (p < 0.00002). An mTICI score of 2b/3 was achieved in 70.2% of patients in the intervention arm. The sICH and mortality in the intervention arm compared with the control arm were 4.7 and 14.3% versus 7.9 and 17.8%, respectively. The NNT and NNH in the intervention and control groups were 5.3 and 9.1, respectively. Patients in the intervention arm had a 50.1% (RPD) better chance of achieving a good 90-day outcome as compared to controls. Conclusions: Endovascular therapy combined with IV tPA (in appropriately selected patients) for LVO-related AIS is superior to IV tPA alone. These results support establishing an endovascular therapy in addition to IV tPA as the standard of care for AIS secondary to LVO.

Safety and Efficacy of a 3-Dimensional Stent Retriever With Aspiration-Based Thrombectomy vs Aspiration-Based Thrombectomy Alone in Acute Ischemic Stroke Intervention: A Randomized Clinical Trial

Importance The treatment effects of individual mechanical thrombectomy devices in large-vessel acute ischemic stroke (AIS) remain unclear. Objective To determine whether the novel 3-dimensional (3-D) stent retriever used in conjunction with an aspiration-based mechanical thrombectomy device (Penumbra System; Penumbra) is noninferior to aspiration-based thrombectomy alone in AIS. Design, Setting, and Participants This randomized, noninferiority clinical trial enrolled patients at 25 North American centers from May 19, 2012, through November 19, 2015, with follow-up for 90 days. Adjudicators of the primary end points were masked to treatment allocation. Patients with large-vessel intracranial occlusion AIS presenting with a National Institutes of Health Stroke Scale (NIHSS) score of at least 8 within 8 hours of onset underwent 1:1 randomization to 3-D stent retriever with aspiration or aspiration alone. The primary analyses were conducted in the intention-to-treat population. Interventions Mechanical thrombectomy using intracranial aspiration with or without the 3-D stent retriever. Main Outcomes and Measures The primary effectiveness end point was the rate of a modified Thrombolysis in Cerebral Infarction (mTICI) grade of 2 to 3 with a 15% noninferiority margin. Device- and procedure-related serious adverse events at 24 hours were the primary safety end points. Results Of 8082 patients screened, 198 patients were enrolled (111 women [56.1%] and 87 men [43.9%]; mean [SD] age, 66.9 [13.0] years) and randomized, including 98 in the 3-D stent retriever with aspiration group and 100 in the aspiration alone group; an additional 238 patients were eligible but not enrolled. The median baseline NIHSS score was 18.0 (interquartile range, 14.0-23.0). Eighty-two of 94 patients in the 3-D stent retriever and aspiration group (87.2%) had an mTICI grade of 2 to 3 compared with 79 of 96 in the aspiration alone group (82.3%; difference, 4.9%; 90% CI, −3.6% to 13.5%). None of the other measures were significantly different between the 2 groups. Device-related serious adverse events were reported by 4 of 98 patients in the 3-D stent retriever with aspiration group (4.1%) vs 5 of 100 patients in the aspiration only group (5.0%); procedure-related serious adverse events, 10 of 98 (10.2%) vs 14 of 100 (14.0%). A 90-day modified Rankin Scale score of 0 to 2 was reported by 39 of 86 patients in the 3-D stent retriever with aspiration group (45.3%) vs 44 of 96 patients in the aspiration only group (45.8%). Conclusions and Relevance The present study provides class 1 evidence for the noninferiority of the 3-D stent retriever with aspiration vs aspiration alone in AIS. Future trials should evaluate whether these results can be generalized to other stent retrievers. Trial Registration clinicaltrials.gov Identifier: NCT01584609