Quiz Ref ID Seven randomized clinical trials have consistently demonstrated that patients with a large vessel occlusion in the anterior circulation benefit from endovascular treatment following intravenous thrombolysis (IVT).^1-7 However, IVT prior to endovascular treatment has potential benefits and risks. Intravenous thrombolysis may sometimes contribute to reperfusion, averting the need for endovascular treatment.⁵ Intravenous thrombolysis may facilitate endovascular reperfusion and promote dissolution of downstream microemboli improving distal perfusion.^8,9 Conversely, IVT may increase the risk of intracranial or systemic hemorrhage, lead to thrombus fragmentation and worsening distal perfusion, and delay the start of the endovascular treatment.^10,11 Furthermore, IVT limits the use of antithrombotic therapy within 24-hour, and increases health care costs.¹²

Acute basilar artery occlusion (BAO) is a rare but potentially catastrophic medical condition accounting for 1% of all ischemic strokes and 5% of large vessel occlusion (LVO) strokes.^1,2 Despite recent advances in the treatment of acute stroke, up to 68% of the patients with acute BAO die or remain severely disabled.^3,4 Early recanalization of an occluded artery in acute stroke has been proven to be associated with favorable functional outcomes.⁵ Recanalization treatments include intravenous thrombolysis (IVT), intra-arterial thrombolysis, mechanical thrombectomy (MT), angioplasty, stenting, or combination therapies.² Although intravenous recombinant tissue plasminogen activator (rt-PA; Alteplase) remains the first-line treatment for acute ischemic stroke (AIS), its benefit is hampered by a short therapeutic window and limited recanalization in LVO strokes.⁶

Endovascular treatment has been shown to significantly increase the reperfusion rate and improve the functional outcomes of patients with acute ischemic stroke due to large vessel occlusion.^1-4 However, endovascular thrombectomy has historically failed to yield successful reperfusion in approximately 30% of patients.⁵ Unsuccessful reperfusion likely arises in part from mechanical thrombectomy devices causing traumatic damage to the vascular endothelium with subendothelial matrix exposure, leading to platelet activation, adhesion, and aggregation and potentially resulting in reocclusion and thromboembolic complications.^6,7

The effects of the glycoprotein IIb/IIIa receptor inhibitor tirofiban in patients with acute ischemic stroke but who have no evidence of complete occlusion of large or medium-sized vessels have not been extensively studied. In a multicenter trial in China, we enrolled patients with ischemic stroke without occlusion of large or medium-sized vessels and with a National Institutes of Health Stroke Scale score of 5 or more and at least one moderately to severely weak limb. Eligible patients had any of four clinical presentations: ineligible for thrombolysis or thrombectomy and within 24 hours after the patient was last known to be well; progression of stroke symptoms 24 to 96 hours after onset; early neurologic deterioration after thrombolysis; or thrombolysis with no improvement at 4 to 24 hours. Patients were assigned to receive intravenous tirofiban (plus oral placebo) or oral aspirin (100 mg per day, plus intravenous placebo) for 2 days; all patients then received oral aspirin until day 90. The primary efficacy end point was an excellent outcome, defined as a score of 0 or 1 on the modified Rankin scale (range, 0 [no symptoms] to 6 [death]) at 90 days. Secondary end points included functional independence at 90 days and a quality-of-life score. The primary safety end points were death and symptomatic intracranial hemorrhage. A total of 606 patients were assigned to the tirofiban group and 571 to the aspirin group. Most patients had small infarctions that were presumed to be atherosclerotic. The percentage of patients with a score of 0 or 1 on the modified Rankin scale at 90 days was 29.1% with tirofiban and 22.2% with aspirin (adjusted risk ratio, 1.26; 95% confidence interval, 1.04 to 1.53, P = 0.02). Results for secondary end points were generally not consistent with the results of the primary analysis. Mortality was similar in the two groups. The incidence of symptomatic intracranial hemorrhage was 1.0% in the tirofiban group and 0% in the aspirin group. In this trial involving heterogeneous groups of patients with stroke of recent onset or progression of stroke symptoms and nonoccluded large and medium-sized cerebral vessels, intravenous tirofiban was associated with a greater likelihood of an excellent outcome than low-dose aspirin. Incidences of intracranial hemorrhages were low but slightly higher with tirofiban. (Funded by the National Natural Science Foundation of China; RESCUE BT2 Chinese Clinical Trial Registry number, ChiCTR2000029502.).

Aim: Although lactate supplementation at the reperfusion stage of ischemic stroke has been shown to offer neuroprotection, whether the role of accumulated lactate at the ischemia phase is neuroprotection or not remains largely unknown. Thus, in this study, we aimed to investigate the roles and mechanisms of accumulated brain lactate at the ischemia stage in regulating brain injury of ischemic stroke.

Background and Objectives There is growing evidence for endovascular thrombectomy (EVT) in patients with large ischemic core infarct and large vessel occlusion. The objective of this study was to compare the efficacy and safety of EVT versus medical management (MM) via a systematic review and meta-analysis of observational studies and randomized controlled trials (RCTs). Methods We searched the PubMed, Embase, Cochrane Library, and Web of Science databases to obtain articles related to mechanical thrombectomy for large ischemic core from inception until February 10, 2023. The primary outcome was independent ambulation (modified Rankin Scale [mRS] 0-3). Effect sizes were computed as risk ratio (RR) with random-effect or fixed-effect models. The quality of articles was evaluated through the Cochrane risk assessment tool and Newcastle-Ottawa scale. This study was registered in PROSPERO (CRD42023396232). Results A total of 5395 articles were obtained through the search and articles that did not meet the inclusion criteria were excluded by review of the title, abstract, and full text. Finally, 3 RCTs and 10 cohort studies met the inclusion criteria. The RCT analysis showed that EVT improved the 90-day functional outcomes of patients with large ischemic core with high-quality evidence, including independent ambulation (mRS 0-3: RR 1.78, 95% CI 1.28-2.48, P < 0.001) and functional independence (mRS 0-2: RR 2.59, 95% CI 1.89-3.57, P < 0.001), but without significantly increasing the risk of symptomatic intracranial hemorrhage (sICH: RR 1.83, 95% CI: 0.95-3.55, P = 0.07) or early mortality (RR 0.95, 95% CI 0.78-1.16, P = 0.61). Analysis of the cohort studies showed that EVT improved functional outcomes of patients without an increase in the incidence in sICH. Conclusion This systematic review and meta-analysis indicates that in patients with large vessel occlusion stroke with a large ischemic core, EVT was associated with improved functional outcomes over medical management without increasing sICH risk. Results of ongoing RCTs may provide further insight in this patient population.