Targeting Recombinant Tissue-Type Plasminogen Activator in Acute Ischemic Stroke Based on Risk of Intracranial Hemorrhage or Poor Functional Outcome An Analysis of the Third International Stroke Trial
ABSTRACT Intravenous recombinant tissue-type plasminogen activator (rtPA), despite a risk of early symptomatic intracranial hemorrhage (sICH), is of net clinical benefit to acute stroke patients. We tested if predictive models could identify patients least likely to be harmed by sICH or those who gained no net benefit.
We used the Third International Stroke Trial (IST-3) trial data set, an international, multicenter, open treatment randomized trial of 0.9 mg/kg rtPA versus control in 3035 patients with acute ischemic stroke. We compared the discrimination and calibration of previously developed predictive models for ICH and poststroke poor outcome and developed a new model using variables selected by systematic review. We calculated the absolute and relative risk reduction of death or dependency with rtPA in patients at a low, medium, or high predicted risk of sICH or poor functional outcome.
Prediction models for sICH or poor outcome (Hemorrhage After Thrombolysis [HAT]; Sugar, Early Infarct Signs, Dense Artery, Age, National Institutes of Health (NIH) Stroke Score (SEDAN); Glucose Race Age Sex Pressure Stroke Severity [GRASPS]; Stroke Thrombolytic Predictive Instrument; Dense Artery, Rankin Score, Age, Glucose, Onset to Treatment Time, NIHSS [DRAGON]; Totaled Health Risk in Vascular Events [THRIVE]; our new model; and a model with National Institutes of Health Stroke Scale and age) had similar area under receiver operator characteristic curves (AUROCC) to predict sICH (P for difference >0.05). The simplest model (with covariates National Institutes of Health Stroke Scale and age) predicted both sICH (AUROCC, 0.63; 95% CI, 0.58-0.68) and poststroke poor functional outcome (AUROCC, 0.80; 95% CI, 0.77-0.82) similarly to complex models. There was no evidence that the effect of rtPA in patients at high predicted risk of sICH or poor functional outcome after stroke was less than in those at lower risk.
There is a clinically relevant net positive effect of rtPA in patients with acute stroke at a high predicted risk of sICH or poor functional outcome.
http://www.controlled-trials.com. Unique identifier: ISRCTN25765518.
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ABSTRACT: Stroke is an acute cerebrovascular disease caused by acute brain artery bursting or cerebral embolism that leads to neuronal death and severe dysfunction of synaptic transmission. Neuronal damage after stroke remains a major cause of morbidity and mortality worldwide and affects 795 000 of lives every year in United States. However, effective treatments remain lacking, which makes the identification of new therapeutic targets a matter of great importance. N-methyl-D-aspartate glutamate (NMDA) receptor is important both in the normal synaptic transmission and in the neuronal death after stroke. Accumulated evidences show NMDA receptor downstream effectors, such as PSD-95, DAPK1, and ERK, had been revealed to be linked with neuronal damage. Based on our recent studies, we review the promising targets of the NMDA receptor downstream signaling involved in stroke treatment. This review will provide the concept of NR2B downstream signaling in neuronal death after stroke and provide evidences for developing better NMDAR-based therapeutics by targeting downstream proteins.07/2014; 2(1):8. DOI:10.1186/2050-490X-2-8
- Value in Health 11/2013; 16(7). DOI:10.1016/j.jval.2013.08.1257 · 2.89 Impact Factor
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ABSTRACT: The primary objective of this sub analysis of the CONOCES study was to analyse outcomes in terms of mortality rates, quality of life and degree of autonomy over the first year in patients admitted to stroke units in Spain. The secondary objective was to identify the factors determining good prognosis. We studied a sample of patients who had suffered a confirmed stroke and been admitted to a Stroke Unit in the Spanish healthcare system. Socio-demographic and clinical variables and variables related to the level of severity (NIHSS), the level of autonomy (Barthel, modified Rankin) and quality of life (EQ-5D) were recorded at the time of admission and then three months and one year after the event. Factors determining prognosis were analysed using logistic regression and ROC curves. A total of 321 patients were recruited, 33% of whom received thrombolytic treatment, which was associated with better results on the Barthel and the modified Rankin scales and in terms of the risk of death. Mean quality of life measured through EQ-5D improved from 0.57 at discharge to 0.65 one year later. Full autonomy level measured by Barthel index increased from 30.1% at discharge to 52.8% at one year and by the modified Rankin scale from 51% to 71%. The rates for in-hospital and 1-year mortality were 5.9% and 17.4% respectively. Low NIHSS scores were associated with a good prognosis with all the outcome variables. The three instruments applied (NIHSS, Barthel and modified Rankin scales) on admission showed good discriminative ability for patient prognosis in the ROC curves. There has been a change in the prognosis for stroke in Spain in recent years as the quality of life at 1 year observed in our study is clearly higher than that obtained in other Spanish studies conducted previously. Moreover, survival and functional outcome have also improved following the introduction of a new model of care. These results clearly promote extension of the model based on stroke units and reinforced rehabilitation to the majority of the more than 100,000 strokes that occur annually in Spain.Health and Quality of Life Outcomes 12/2015; 13(1):230. DOI:10.1186/s12955-015-0230-8 · 2.10 Impact Factor