Systematic Review of Outcome After Ischemic Stroke Due to Anterior Circulation Occlusion Treated With Intravenous, Intra-Arterial, or Combined Intravenous+Intra-Arterial Thrombolysis

Abstract

Background and Purpose-The optimal approach to recanalization in acute ischemic stroke is unknown. We performed a literature review and meta-analysis comparing the relative efficacy of 6 reperfusion strategies: (1) 0.9 mg/kg intravenous tissue-type plasminogen activator; (2) intra-arterial chemical thrombolysis; (3) intra-arterial mechanical thrombolysis; (4) intra-arterial combined chemical/mechanical thrombolysis; (5) 0.6 mg/kg intravenous tissue-type plasminogen activator and intra-arterial thrombolysis; and (6) 0.9 mg/kg intravenous tissue-type plasminogen activator and intra-arterial thrombolysis. Methods-A literature search in Medline, Embase, and the Cochrane database identified case series, observational studies, and treatment arms of randomized trials of anterior circulation arterial occlusion treated with thrombolytic therapy. Included studies had Ն10 subjects, mean time to treatment Ͻ6 hours, and treatment specific reporting of disability, death, and intracerebral hemorrhage. Multivariable metaregression evaluated the effects of treatment group on outcome at the same time as accounting for differences in baseline covariates. Results-A total of 2986 abstracts were identified from which 54 studies (5019 subjects) were included. There were significant differences across groups in age (Pϭ0.0008), baseline National Institutes of Health Stroke Scale (Pϭ0.0002), and time to treatment initiation (PϽ0.0001). There were also differences in mean modified Rankin Scale (PϽ0.0001), mortality (Pϭ0.0024), and symptomatic intracerebral hemorrhage (Pϭ0.0305). Differences in modified Rankin Scale were not significant in the metaregression and likely attributable to differences in baseline covariates between studies. Key Words: infarction Ⅲ meta-analysis Ⅲ thrombolysis Ⅲ thrombectomy S troke is the fourth leading cause of death in the United States and a leading cause of disability. 1 Stroke due to large-artery occlusion has a particularly poor prognosis with higher rates of death and disability than other stroke subtypes. 2-4 Current acute ischemic stroke interventions attempt to recanalize occluded arteries thereby restoring cerebral blood flow and improving functional outcome. The most well studied of these therapies is intravenous (IV) tissue-type plasminogen activator (tPA). Alternative strategies are available and have been used in both clinical practice and clinical research, including intra-arterial (IA) thrombolysis (chemical/ mechanical) and combined IVϩIA thrombolysis; however, the relative efficacy of these approaches is unknown. [5][6][7][8] IV tPA is recommended as the first-line therapy for patients with acute ischemic stroke presenting within 4.5 hours of symptom onset. 9,10 Unfortunately, recanalization rates with IV tPA are low when a large-artery occlusion is present with rates ranging from 4% to 68% depending on the study and the location of the occlusion. 11-13 A recent meta-analysis found a 46% recanalization rate overall with IV tPA. Small studies suggest that endovascular thrombolysis may be a fea...

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