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In acute ischemic stroke, a longer time from onset to endovascular treatment (EVT) is associated with worse clinical outcome. We investigated the association of clinical outcome with time from last known well to arrival at the EVT hospital and time from hospital arrival to arterial access for anterior circulation large vessel occlusion patients treated > 6 hours from last known well.
Methods:
Retrospective analysis of the prospective, multicenter cohort study ESCAPE-LATE. Patients presenting > 6 hours after last known well with anterior circulation large vessel occlusion undergoing EVT were included. The primary outcome was the modified Rankin Scale (mRS) score at 90 days. Secondary outcomes were good (mRS 0–2) and poor clinical outcomes (mRS 5–6) at 90 days, as well as the National Institutes of Health Stroke Scale at 24 hours. Associations of time intervals with outcomes were assessed with univariable and multivariable logistic regression.
Results:
Two hundred patients were included in the analysis, of whom 85 (43%) were female. 90-day mRS was available for 141 patients. Of the 150 patients, 135 (90%) had moderate-to-good collaterals, and the median Alberta Stroke Program Early CT Score (ASPECTS) was 8 (IQR = 7–10). No association between ordinal mRS and time from last known well to arrival at the EVT hospital (odds ratio [OR] = 1.01, 95% CI = 1.00–1.02) or time from hospital arrival to arterial access (OR = -0.01, 95% CI = -0.02–0.00) was seen in adjusted regression models.
Conclusion:
No relationship was observed between pre-hospital or in-hospital workflow times and clinical outcomes. Baseline ASPECTS and collateral status were favorable in the majority of patients, suggesting that physicians may have chosen to predominantly treat slow progressors in the late time window, in whom prolonged workflow times have less impact on outcomes.
To assess cost-effectiveness of late time-window endovascular treatment (EVT) in a clinical trial setting and a “real-world” setting.
Methods:
Data are from the randomized ESCAPE trial and a prospective cohort study (ESCAPE-LATE). Anterior circulation large vessel occlusion patients presenting > 6 hours from last-known-well were included, whereby collateral status was an inclusion criterion for ESCAPE but not ESCAPE-LATE. A Markov state transition model was built to estimate lifetime costs and quality-adjusted life-years (QALYs) for EVT in addition to best medical care vs. best medical care only in a clinical trial setting (comparing ESCAPE-EVT to ESCAPE control arm patients) and a “real-world” setting (comparing ESCAPE-LATE to ESCAPE control arm patients). We performed an unadjusted analysis, using 90-day modified Rankin Scale(mRS) scores as model input and analysis adjusted for baseline factors. Acceptability of EVT was calculated using upper/lower willingness-to-pay thresholds of 100,000 USD/50,000 USD/QALY.
Results:
Two-hundred and forty-nine patients were included (ESCAPE-LATE:n = 200, ESCAPE EVT-arm:n = 29, ESCAPE control-arm:n = 20). Late EVT in addition to best medical care was cost effective in the unadjusted analysis both in the clinical trial and real-world setting, with acceptability 96.6%–99.0%. After adjusting for differences in baseline variables between the groups, late EVT was marginally cost effective in the clinical trial setting (acceptability:49.9%–61.6%), but not the “real-world” setting (acceptability:32.9%–42.6%).
Conclusion:
EVT for LVO-patients presenting beyond 6 hours was cost effective in the clinical trial setting and “real-world” setting, although this was largely related to baseline patient differences favoring the “real-world” EVT group. After adjusting for these, EVT benefit was reduced in the trial setting, and absent in the real-world setting.
In the past decade, there have been considerable advances in the endovascular management of patients with acute ischaemic stroke. However, notwithstanding the clear cut evidence for endovascular therapy there remain major logistical challenges in providing widespread and timely access to this therapy across many healthcare systems. For those patients who either fail endovascular therapy, or who present outside the time dependent therapeutic window, there is a risk that they will go on to develop life threatening cerebral oedema, so-called malignant middle cerebral artery infarction. The prognosis for these patients is poor with a mortality rate in the region of 80%, without specific treatment. In these circumstances, consideration may be given to performing a decompressive hemicraniectomy as a lifesaving intervention. Unfortunately, unlike endovascular therapy that has the potential to reverse a neurological deficit, surgical decompression will only reduce mortality and the concern has always been that many survivors will be left with an unacceptable level of disability. There have now been a number of randomized controlled trials that have demonstrated this outcome, and this presents a number of ethical issues that require consideration when faced with a patient who clinically deteriorates following an ischaemic stroke.
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