Dataset Information

A new era for stroke therapy: Integrating neurovascular protection with optimal reperfusion.

ABSTRACT: Recent advances in stroke reperfusion therapies have led to remarkable improvement in clinical outcomes, but many patients remain severely disabled, due in part to the lack of effective neuroprotective strategies. In this review, we show that 95% of published preclinical studies on "neuroprotectants" (1990-2018) reported positive outcomes in animal models of ischemic stroke, while none translated to successful Phase III trials. There are many complex reasons for this failure in translational research, including that the majority of clinical trials did not test early delivery of neuroprotectants in combination with successful reperfusion. In contrast to the clinical trials, >80% of recent preclinical studies examined the neuroprotectant in animal models of transient ischemia with complete reperfusion. Furthermore, only a small fraction of preclinical studies included long-term functional assessments, aged animals of both genders, and models with stroke comorbidities. Recent clinical trials demonstrate that 70%-80% of patients treated with endovascular thrombectomy achieve successful reperfusion. These successes revive the opportunity to retest previously failed approaches, including cocktail drugs that target multiple injury phases and different cell types. It is our hope that neurovascular protectants can be retested in future stroke research studies with specific criteria outlined in this review to increase translational successes.

SUBMITTER: Shi L

PROVIDER: S-EPMC6282224 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

A new era for stroke therapy: Integrating neurovascular protection with optimal reperfusion.

Shi Ligen L Rocha Marcelo M Leak Rehana K RK Zhao Jingyan J Bhatia Tarun N TN Mu Hongfeng H Wei Zhishuo Z Yu Fang F Weiner Susan L SL Ma Feifei F Jovin Tudor G TG Chen Jun J

Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism 20180907 12

Recent advances in stroke reperfusion therapies have led to remarkable improvement in clinical outcomes, but many patients remain severely disabled, due in part to the lack of effective neuroprotective strategies. In this review, we show that 95% of published preclinical studies on "neuroprotectants" (1990-2018) reported positive outcomes in animal models of ischemic stroke, while none translated to successful Phase III trials. There are many complex reasons for this failure in translational res ...[more]

PMID: 30191760

Similar Datasets

Project description:ImportanceA significant proportion of acute ischemic strokes occur while patients are hospitalized. Limited contemporary data exist on the utilization rates of intravenous thrombolysis or endovascular therapy for in-hospital stroke.ObjectiveTo use a national registry to examine temporal trends in the use of intravenous and endovascular reperfusion therapies for treatment of in-hospital stroke.Design, setting, and participantsThis retrospective cohort study analyzed data from 267 956 patients who underwent reperfusion therapy for stroke with in-hospital or out-of-hospital onset reported in the Get With the Guidelines-Stroke national registry from January 2008 to September 2018.ExposuresIn-hospital onset vs out-of-hospital onset of stroke symptoms.Main outcomes and measuresTemporal trends in the use of reperfusion therapy, process measures of quality, and the association between functional outcomes and key patient characteristics, comorbidities, and treatments.ResultsOf 67 493 patients with in-hospital stroke onset, this study observed increased rates of vascular risk factors (standardized mean difference >10%) but no significant differences in age or sex in patients undergoing intravenous thrombolysis only (mean [interquartile range {IQR}] age, 72 [80-62] y; 53.2% female) or those undergoing endovascular therapy (mean [IQR] age, 69 [59-79] y; 49.8% female). Of these patients, 10 481 (15.5%) received intravenous thrombolysis and 2494 (3.7%) underwent endovascular therapy. Compared with 2008, in 2018 the proportion of in-hospital stroke among all stroke hospital discharges was higher (3.5% vs 2.7%; P < .001), as was use of intravenous thrombolysis (19.1% vs 9.1%; P < .001) and endovascular therapy (6.4% vs 2.5%; P < .001) in patients with in-hospital stroke, with a significant increase in endovascular therapy in mid-2015 (P < .001). Compared with patients who received intravenous thrombolysis for out-of-hospital stroke onset, those with in-hospital onset were associated with longer median (IQR) times from stroke recognition to cranial imaging (33 [18-60] vs 16 [9-26] minutes; P < .001) and to thrombolysis bolus (81 [52-125] vs 60 [45-84] minutes; P < .001). In adjusted analyses, patients with in-hospital stroke onset who were treated with intravenous thrombolysis were less likely to ambulate independently at discharge (adjusted odds ratio, 0.78; 95% CI, 0.74-0.82; P < .001) and were more likely to die or to be discharged to hospice (adjusted odds ratio, 1.39; 95% CI, 1.29-1.50; P < .001) than patients with out-of-hospital onset who also received intravenous thrombolysis treatment. Comparisons among patients treated with endovascular therapy yielded similar findings.Conclusions and relevanceIn this cohort study, in-hospital stroke onset was increasingly reported and treated with reperfusion therapy. Compared with out-of-hospital stroke onset, in-hospital onset was associated with longer delays to reperfusion and worse functional outcomes, highlighting opportunities to further care for patients with in-hospital stroke onset.

Dataset Information

A new era for stroke therapy: Integrating neurovascular protection with optimal reperfusion.

Publications

A new era for stroke therapy: Integrating neurovascular protection with optimal reperfusion.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure