Ischemic strokes due to large-vessel occlusions contribute disproportionately to stroke-related dependence and death: A review

Abstract

Background: Since large-vessel occlusion (LVO)-related acute ischemic strokes (AIS) are associated with more severe deficits, we hypothesize that the endovascular thrombectomy (ET) may disproportionately benefit stroke-related dependence and death. Methods: To delineate LVO-AIS impact, systematic search identified studies measuring dependence or death [modified Rankin Scale (mRS) 3-6] or mortality following ischemic stroke among consecutive patients presenting with both LVO and non-LVO events within 24 h of symptom onset. Results: Among 197 articles reviewed, 2 met inclusion criteria, collectively enrolling 1,467 patients. Rates of dependence or death (mRS 3-6) within 3-6 months were higher after LVO than non-LVO ischemic stroke, 64 vs. 24%, odds ratio (OR) 4.46 (CI: 3.53-5.63, p < 0.0001). Mortality within 3-6 months was higher after LVO than non-LVO ischemic stroke, 26.2 vs. 1.3%, OR 4.09 (CI: 2.5-6.68), p < 0.0001. Consequently, while LVO ischemic events accounted for 38.7% (CI: 21.8-55.7%) of all acutely presenting ischemic strokes, they accounted for 61.6% (CI: 41.8-81.3%) of poststroke dependence or death and 95.6% (CI: 89.0-98.8%) of poststroke mortality. Using literature-based projections of LVO cerebral ischemia patients treatable within 8 h of onset, ET can be used in 21.4% of acutely presenting patients with ischemic stroke, and these events account for 34% of poststroke dependence and death and 52.8% of poststroke mortality. Conclusion: LVOs cause a little more than one-third of acutely presenting AIS, but are responsible for three-fifths of dependency and more than nine-tenths of mortality after AIS. At the population level, ET has a disproportionate benefit in reducing severe stroke outcomes. Acute ischemic stroke (AIS) is a leading cause of morbidity and mortality worldwide (1). The advent of endovascular thrombectomy (ET) as a proven beneficial treatment for acute cerebral ischemia is a major advance in neurovascular therapeutics (2, 3). But concerns have been raised that treatment impact may be modest at the population level, as ET is appropriate only for the subset of patients with cerebral ischemia due to occlusions of large, proximal arteries that are accessible to thrombectomy devices. Analyses of the potential general impact of ET have largely focused upon the proportion of patients treatable with the intervention and estimated at 4-18% of all ischemic stroke patients (4, 5). However, such analyses almost certainly underestimate the impact of thrombectomy treatment on stroke outcomes. Ischemic strokes due to large-vessel occlusions (LVOs), compared with non-LVO strokes, are larger in infarct size (6, 7), have more severe presenting deficits (8, 9), and have worse long-term outcomes (10, 11). LVO ischemic strokes, therefore, are likely to contribute disproportionately to population-level poststroke dependence and mortality, higher than their simple frequency of occurrence among acutely presenting patients. We, therefore, undertook a focused, meta-analytic review to delineate the frequency of LVO ischemic strokes and their relative contribution to stroke-related disability and death among all patients presenting with acute cerebral ischemia.