Trends in Use, Outcomes, and Disparities in Endovascular Thrombectomy in US Patients With Stroke Aged 80 Years and Older Compared With Younger Patients

Adcock, Amelia; Schwamm, Lee H; Smith, Eric E.; Fonarow, Gregg C.; Reeves, Mathew J.; Xu, Haolin; Matsouaka, Roland; Xian, Ying; Saver, Jeffrey L.

doi:10.1001/jamanetworkopen.2022.15869

Cited by 24 publications

(15 citation statements)

References 35 publications

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“…First, the use of recanalization therapies including either intravenous lytic therapy or mechanical thrombectomy continue to increase as knowledge of their clinical benefit grows. [41][42][43] Therefore, the number of stroke patients with a transient occlusion will continue to increase in the coming years. Second, spontaneous reperfusion occurs in a significant number of stroke patients, 44 and understanding the brain's response to reperfusion injury remains relevant to develop therapeutics that improve long-term stroke outcomes.…”

Section: Discussionmentioning

confidence: 99%

Targeting BACE1-mediated production of amyloid beta improves hippocampal synaptic function in an experimental model of ischemic stroke

Basak

Falk

Mitchell

et al. 2023

J Cereb Blood Flow Metab

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Post-stroke cognitive impairment and dementia (PSCID) affects many survivors of large vessel cerebral ischemia. The molecular pathways underlying PSCID are poorly defined but may overlap with neurodegenerative pathophysiology. Specifically, synaptic dysfunction after stroke may be directly mediated by alterations in the levels of amyloid beta (Aβ), the peptide that accumulates in the brains of Alzheimer’s disease (AD) patients. In this study, we use the transient middle cerebral artery occlusion (MCAo) model in young adult mice to evaluate if a large vessel stroke increases brain soluble Aβ levels. We show that soluble Aβ40 and Aβ42 levels are increased in the ipsilateral hippocampus in MCAo mice 7 days after the injury. We also analyze the level and activity of β-site amyloid precursor protein cleaving enzyme 1 (BACE1), an enzyme that generates Aβ in the brain, and observe that BACE1 activity is increased in the ipsilateral hippocampus of the MCAo mice. Finally, we highlight that treatment of MCAo mice with a BACE1 inhibitor during the recovery period rescues stroke-induced deficits in hippocampal synaptic plasticity. These findings support a molecular pathway linking ischemia to alterations in BACE1-mediated production of Aβ, and encourage future studies that evaluate whether targeting BACE1 activity improves the cognitive deficits seen with PSCID.

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Section: Discussionmentioning

confidence: 99%

Targeting BACE1-mediated production of amyloid beta improves hippocampal synaptic function in an experimental model of ischemic stroke

Basak

Falk

Mitchell

et al. 2023

J Cereb Blood Flow Metab

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“…A recent US nationwide retrospective cohort study using the Get with the Guidelines-Stroke (GWTG-Stroke) program [16] demonstrates steady increase in the use of EVT in patients aged 80 years and older from 3.3% in quarter 3 of 2012 to 20.8% in quarter 2 of 2019 in the study cohort (n = 12,768). This trend was similar for patients <80 (n = 29,654) during the same time period.…”

Section: Discussionmentioning

confidence: 99%

Efficacy of Endovascular Thrombectomy in the Oldest Old (Stroke 90+ Study): A Community Center Experience

Brant‐Zawadzki

Mastrolia

Hara

et al. 2023

Preprint

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Background: While endovascular thrombectomy (EVT) is considered as the most effective treatment for a select group of patients with acute ischemic stroke and large vessel occlusion, its safety and efficacy in older patients are still debated especially in read-world settings. This study reports outcomes of EVT in acute ischemic stroke patients aged 90 and older in our community hospital setting. Methods: Data between January 2018 and December 2022 were aggregated for all acute ischemic stroke patients with aged 90 and older at the time of EVT. Thirty-one patients met the criteria and were included in this report. The data valuables included, but are not limited to, demographics, stroke risk factors, thrombolysis in cerebral infarction (TICI), modified Rankin Scale (mRS), and NIH Stroke Scale (NIHSS). Results: All 31 patients had improvement in TICI scale. One had symptomatic intracranial hemorrhage after EVT not related to the procedure, but likely on the basis of reperfusion breakthrough. Three patients expired prior to their discharge from non-stroke related causes. Of remaining 28, four expired, six went into hospice care, and four lost to follow-up by 30-days post DC. Of six hospice cases, one expired by 90-day post DC, and additional three were lost to follow-up. Given this data, 20/27 (74%) survived to 30 days and 16/24 (67%) to 90 days. For their NIHSS symptomatic categories, 15/28 (54%) patients improved, 10/28 (36%) remained the same, and 3/28 (11%) declined. For mRS, at 30-days post DC, 7/24 (30%) patients showed improvement, 7/24 (30%) remained the same, and 10/24 (40%) declined. At 90-days post DC, 7/21 (33%) showed improvement from DC, 4/21 (19%) remained the same, and 10/21 (48%) declined. Conclusions: While a larger cohort study is necessary, our report supports the safety and efficacy of EVT in this patient aged 90 and older in a real-world setting.

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“…47 Still, in randomized clinical trials, only one-third of the patients end up disability-free at day 90, and this rate may be even lower in standard clinical practice. 48 There is a critical need to unveil interventions that improve the overall benefits of endovascular therapy. 49 Arguably, a reason for the limited success of MT, despite impressive rates of large vessel recanalization, can be found in the microcirculation.…”

Section: The Span Success Storymentioning

confidence: 99%

Uric Acid

Leira,

Planas,

Chauhan

et al. 2023

Neurology

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Uric acid (UA) is a strong endogenous antioxidant that neutralizes the toxicity of peroxynitrite and other reactive species on the neurovascular unit generated during and after acute brain ischemia. The realization that a rapid reduction of UA levels during an acute ischemic stroke was associated with a worse stroke outcome paved the way to investigate the value of exogenous UA supplementation to counteract the progression of redox-mediated ischemic brain damage. The long translational journey for UA supplementation recently reached a critical milestone when the results of the multicenter NIH stroke preclinical assessment network (SPAN) were reported. In a novel pre-clinical paradigm, six treatment candidates including UA supplementation were selected and tested in six independent laboratories following predefined criteria and strict methodological rigor. UA supplementation was the only intervention in SPAN that exceeded the pre-specified efficacy boundary with males and females, young mice, young rats, aging mice, obese mice, and spontaneously hypertensive rats. This unprecedented achievement will allow UA to undergo clinical testing in a pivotal clinical trial through a NIH Strokenet Thrombectomy Endovascular Platform (STEP) created to assess new treatment strategies in patients treated with mechanical thrombectomy. UA is a particularly appealing adjuvant intervention for mechanical thrombectomy, as it targets the microcirculatory hypoperfusion and oxidative stress that limits the efficacy of this therapy. This descriptive review aims to summarize the translational development of UA supplementation, highlighting those aspects that likely contributed to its success. It includes having a well-defined target and mechanism of action, and an approach that simultaneously integrated rigorous pre-clinical assessment, with epidemiological and preliminary human intervention studies. Validation of the clinical value of UA supplementation in a pivotal trial would confirm the translational value of the SPAN paradigm in pre-clinical research.

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Trends in Use, Outcomes, and Disparities in Endovascular Thrombectomy in US Patients With Stroke Aged 80 Years and Older Compared With Younger Patients

Cited by 24 publications

References 35 publications

Targeting BACE1-mediated production of amyloid beta improves hippocampal synaptic function in an experimental model of ischemic stroke

Targeting BACE1-mediated production of amyloid beta improves hippocampal synaptic function in an experimental model of ischemic stroke

Efficacy of Endovascular Thrombectomy in the Oldest Old (Stroke 90+ Study): A Community Center Experience

Uric Acid

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