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Outcomes of thrombolytic therapy in acute ischemic stroke: mothership, drip-and-ship, and ship-and-drip paradigms.

ABSTRACT: BACKGROUND:Chulalongkorn Stroke Center is a comprehensive stroke center (CSC) located in Bangkok, Thailand. Our stroke network consists of different levels of spoke hospitals, ranging from community hospitals where thrombolytic treatment is not available, to those capable of onsite thrombolytic therapy. This study aimed to assess the time to treatment and outcomes among acute ischemic stroke patients who received thrombolytic treatment in the Chulalongkorn Stroke Network by 1.) Direct arrival at the CSC (mothership) 2.) Telestroke-assisted thrombolytic treatment with secondary transfer to the CSC (drip-and-ship) 3.) Referral from community hospital to the CSC for thrombolytic treatment (ship-and-drip). METHODS:Acute ischemic stroke patients who received thrombolytic treatment during January 2016-December 2017 in the Chulalongkorn Stroke Network were studied. Time to treatment and clinical outcomes were compared among treatment groups. RESULTS:There were 273 patients in the study including 147, 87, and 39 patients in mothership, drip-and-ship, and ship-and-drip paradigms, respectively. The door-to-needle-time (DTN) and onset-to-needle-time (OTN) times were significantly longest in ship-and-drip group (146.5?±?62/205.03?±?44.88 mins) compared to mothership (38?±?23/155.2?±?60.54 mins) and drip-and-ship (63.0?±?44/166.09?±?87 mins), P?

SUBMITTER: Kijpaisalratana N

PROVIDER: S-EPMC6998331 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Outcomes of thrombolytic therapy in acute ischemic stroke: mothership, drip-and-ship, and ship-and-drip paradigms.

Kijpaisalratana Naruchorn N Chutinet Aurauma A Akarathanawat Wasan W Vongvasinkul Pakkawan P Suwanwela Nijasri C NC

BMC neurology 20200203 1

<h4>Background</h4>Chulalongkorn Stroke Center is a comprehensive stroke center (CSC) located in Bangkok, Thailand. Our stroke network consists of different levels of spoke hospitals, ranging from community hospitals where thrombolytic treatment is not available, to those capable of onsite thrombolytic therapy. This study aimed to assess the time to treatment and outcomes among acute ischemic stroke patients who received thrombolytic treatment in the Chulalongkorn Stroke Network by 1.) Direct ar ...[more]

PMID: 32013906

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Project description:BackgroundSpecific clinical risk factors may contribute to improving or worsening neurological functions in acute ischemic stroke (AIS) patients pre-treated with a combined cholesterol reducer and recombinant tissue plasminogen activator (rtPA) therapy. In this study, clinical risk factors associated with good or poor presenting neurological symptoms in ischemic stroke patients with prior cholesterol reducer use, specifically a statin and rtPA therapy was investigated.MethodsRetrospective data for baseline clinical and demographic data for patients with AIS taking cholesterol reducers prior to rtPA treatment from January 2010 to June 2016 in a regional stroke center was analyzed. Improving (NIHSS score ≤ 7) or worsening (NIHSS score > 7) of neurologic functions were the determined measures of treatment outcome. Multivariate logistic regression models identified demographic and clinical factors associated with worsening or improving neurologic functions.ResultsAdjusted multivariate analysis showed that in an AIS population with a combined rtPA and cholesterol reducer medication history, increasing age (OR = 1.032, 95% CI, 1.015-1.048, P < 0.001) and atrial fibrillation (OR = 1.859, 95% CI, 1.098-3.149, P = 0.021) demonstrated a likely association with worsening neurologic functions, while direct admission (OR = 0.411, 95% CI, 0.246-0.686, P = 0.001) and being Caucasian (OR = 0.496, 95% CI, 0.297-0.827, P = 0.007) showed an association with improving or progressing neurologic functions.ConclusionA prior cholesterol reducer, namely a statin, plus rtPA combination may be associated with worsening neurological function for elderly AIS patients with atrial fibrillation, while Caucasians directly admitted to a neurology unit are more likely to show an association with progress or improvements in neurologic functions. While combining statin with rtPA treatment may facilitate worsening neurologic functions in elderly AIS patients with atrial fibrillation, they should not be denied of this therapy. The decision to combine statin and rtPA for AIS patients with atrial fibrillation can be done after clinical stabilization following appropriate clinical management.

Project description:BackgroundExisting data and clinical trials could not determine whether faster intravenous thrombolytic therapy (IVT) translates into better long-term functional outcomes after acute ischemic stroke among those treated with endovascular thrombectomy (EVT). Patient-level national data can provide the required large population to study the associations between earlier IVT, versus later, with longitudinal functional outcomes and mortality in patients receiving IVT+EVT combined treatment.MethodsThis cohort study included older US patients (age ≥65 years) who received IVT within 4.5 hours or EVT within 7 hours after acute ischemic stroke using the linked 2015 to 2018 Get With The Guidelines-Stroke and Medicare database (38 913 treated with IVT only and 3946 with IVT+EVT). Primary outcome was home time, a patient-prioritized functional outcome. Secondary outcomes included all-cause mortality in 1 year. Multivariate logistic regression and Cox proportional hazards models were used to evaluate the associations between door-to-needle (DTN) times and outcomes.ResultsAmong patients treated with IVT+EVT, after adjusting for patient and hospital factors, including onset-to-EVT times, each 15-minute increase in DTN times for IVT was associated with significantly higher odds of zero home time in a year (never discharged to home) (adjusted odds ratio, 1.12 [95% CI, 1.06-1.19]), less home time among those discharged to home (adjusted odds ratio, 0.93 per 1% of 365 days [95% CI, 0.89-0.98]), and higher all-cause mortality (adjusted hazard ratio, 1.07 [95% CI, 1.02-1.11]). These associations were also statistically significant among patients treated with IVT but at a modest degree (adjusted odds ratio, 1.04 for zero home time, 0.96 per 1% home time for those discharged to home, and adjusted hazard ratio 1.03 for mortality). In the secondary analysis where the IVT+EVT group was compared with 3704 patients treated with EVT only, shorter DTN times (≤60, 45, and 30 minutes) achieved incrementally more home time in a year, and more modified Rankin Scale 0 to 2 at discharge (22.3%, 23.4%, and 25.0%, respectively) versus EVT only (16.4%, P<0.001 for each). The benefit dissipated with DTN>60 minutes.ConclusionsAmong older patients with stroke treated with either IVT only or IVT+EVT, shorter DTN times are associated with better long-term functional outcomes and lower mortality. These findings support further efforts to accelerate thrombolytic administration in all eligible patients, including EVT candidates.

Project description:BackgroundIntravenous administration of fibrinolytic drugs, such as recombinant tissue plasminogen activator (rtPA) is the standard treatment of acute thrombotic diseases. However, current fibrinolytics exhibit limited clinical efficacy because of their short plasma half-lives and risk of hemorrhagic transformations. Platelet membrane-based nanocarriers have received increasing attention for ischemic stroke therapies, as they have natural thrombus-targeting activity, can prolong half-life of the fibrinolytic therapy, and reduce side effects. In this study we have gone further in developing platelet-derived nanocarriers (defined as cellsomes) to encapsulate and protect rtPA from degradation. Following lyophilization and characterization, their formulation properties, biocompatibility, therapeutic effect, and risk of hemorrhages were later investigated in a thromboembolic model of stroke in mice.ResultsCellsomes of 200 nm size and loaded with rtPA were generated from membrane fragments of human platelets. The lyophilization process did not influence the nanocarrier size distribution, morphology, and colloidal stability conferring particle preservation and long-term storage. Encapsulated rtPA in cellsomes and administered as a single bolus showed to be as effective as a continuous clinical perfusion of free rtPA at equal concentration, without increasing the risk of hemorrhagic transformations or provoking an inflammatory response.ConclusionsThis study provides evidence for the safe and effective use of lyophilized biomimetic platelet-derived nanomedicine for precise thrombolytic treatment of acute ischemic stroke. In addition, this new nanoformulation could simplify the clinical use of rtPA as a single bolus, being easier and less time-consuming in an emergency setting than a treatment perfusion, particularly in stroke patients. We have successfully addressed one of the main barriers to drug application and commercialization, the long-term storage of nanomedicines, overcoming the potential chemical and physical instabilities of nanomedicines when stored in an aqueous buffer.

Dataset Information

Outcomes of thrombolytic therapy in acute ischemic stroke: mothership, drip-and-ship, and ship-and-drip paradigms.

Publications

Outcomes of thrombolytic therapy in acute ischemic stroke: mothership, drip-and-ship, and ship-and-drip paradigms.

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