Optimal dose for stroke thrombolysis in Asians: low dose may have similar safety and efficacy as standard dose

Background and Purpose— Various risk score models have been developed to predict symptomatic intracerebral hemorrhage (SICH) after intravenous thrombolysis for acute ischemic stroke. In this study, we aimed to determine the prediction performance of these risk scores in a Taiwanese population Methods— Prospectively collected data from 4 hospitals were used to calculate probability of SICH with the scores developed by Cucchiara et al, the Hemorrhage After Thrombolysis (HAT) score, the Safe Implementation of Thrombolysis in Stroke-SICH risk score, the Glucose Race Age Sex Pressure Stroke Severity score, and the Stroke Prognostication using Age and National Institutes of Health Stroke Scale-100 index. We used logistic regression to evaluate the effectiveness of each risk model in predicting SICH and the c statistic to assess performance. Results— A total of 548 patients were included. The rates of SICH were 7.3% by the National Institute of Neurological Diseases and Stroke definition, 5.3% by the European-Australasian Cooperative Acute Stroke Study II definition, and 3.5% by the Safe Implementation of Thrombolysis in Stroke-Monitoring Study definition. The Cucchiara score, the HAT score, and the Safe Implementation of Thrombolysis in Stroke-SICH risk score were significant predictors of SICH for all 3 definitions, whereas the Glucose Race Age Sex Pressure Stroke Severity score and the Stroke Prognostication using Age and National Institutes of Health Stroke Scale-100 index predicted well only for 1 or 2 definitions of SICH. The c statistic was highest for the HAT score (range, 0.69–0.73) across the definitions of SICH. Conclusions— The Cucchiara score, the HAT score, and the Safe Implementation of Thrombolysis in Stroke-SICH risk score predicted SICH reasonably well regardless of which SICH definition was used. However, only the HAT score had an acceptable discriminatory ability.

Section: Discussionmentioning

confidence: 99%

Comparison of Risk-scoring Systems in Predicting Symptomatic Intracerebral Hemorrhage After Intravenous Thrombolysis

Sung

Chen

Lin

et al. 2013

“…The impact of different r-tPA doses on patient outcomes is rarely discussed in international neurological societies, with the exception of a few small studies in certain Asian countries. 10, 11 The present study is the first that registered enough East Asian patients receiving various doses of r-tPA to analyze the relationship between the dose and the safety/efficacy in acute ischemic stroke. Our study echoes the findings of previous studies that higher doses of thrombolytic agents increase the risk of hemorrhage and reveals higher rates of SICH per the NINDS definition (12.4%) in elderly patients (71-80 years) receiving 0.9 mg/kg of r-tPA (Table III in the onlineonly Data Supplement).…”

Section: Discussionmentioning

confidence: 99%

Different Doses of Recombinant Tissue-Type Plasminogen Activator for Acute Stroke in Chinese Patients

Chao

Liu

Chen

et al. 2014

In America and Europe, the current recommended dose of recombinant tissue-type plasminogen activator (r-tPA) for acute ischemic stroke is 0.9 mg/kg, but a similar study with this dosage has never been replicated in a controlled trial in East Asia. A lower dose (0.6 mg/kg) of r-tPA was used in Japan and was proved to have similar outcomes compared with a dose of 0.9 mg/kg in Western countries.1,2 However, the Safe Implementation of Thrombolysis in Stroke-Non-European Union World (SITS-NEW) study demonstrated that the safety and efficacy of the dose of 0.9 mg/kg of r-tPA in an Asian population was similar to those of the Safe Implementation of Thrombolysis in Stroke-Monitoring Study (SITS-MOST) study in the European population. 3,4 Our previous study, the Taiwan Thrombolytic Therapy for Acute Ischemic Stroke (TTT-AIS) study, was the first to determine whether the thrombolytic therapy in routine clinical use was as safe and effective in Chinese patients as in white patients. 5 The preliminary results showed that the group receiving a dose of 0.9 mg/kg had higher rates of symptomatic intracerebral hemorrhage (SICH), dependence, and mortality within 3 months than the low-dose group (<0.85 mg/kg). This finding was more prominent in older patients aged ≥70 years.Background and Purpose-The relationship between the dose of recombinant tissue-type plasminogen activator (r-tPA) and its safety/efficacy for ischemic stroke has not been well evaluated in the East Asian population. We assessed the safety/efficacy of different doses of r-tPA for acute ischemic stroke in Chinese patients. Methods-A total of 1004 eligible patients were classified according to the dose of r-tPA received for managing acute ischemic stroke: 0.9 mg/kg (n=422), 0.8 mg/kg (n=202), 0.7 mg/kg (n=199), and 0.6 mg/kg (n=181). The safety outcome was symptomatic intracerebral hemorrhage and death within 3 months. The efficacy outcome was good functional outcome (modified Rankin Scale ≤1) at 3 months. Results-There was a significant trend for symptomatic intracerebral hemorrhage with age (P=0.002). With multivariate logistic regression analysis, a dose of 0.9 mg/kg was a predictor of symptomatic intracerebral hemorrhage (P=0.0109), and a dose ≤0.65 mg/kg was a predictor of good functional outcome (P=0.0369). In patients aged 71 to 80 years, there was a significant trend of increasing symptomatic intracerebral hemorrhage (P=0.0130) and less good functional outcome (P=0.0179) with increasing doses of r-tPA. There was also a trend of increasing mortality (P=0.0971) at 3 months in these patients. Conclusions-These

“…7,[17][18][19][20] The sample sizes of these studies were small, and usually only one low-dose regimen was compared with the standard dose. The results of these studies were often contradictory.…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, there is controversy on the optimal dose of tPA. In Asia, many hospitals chose a low-dose or even variable-dose IV-tPA regimens [5][6][7][8][9] because of the belief that there is racial differences in blood coagulation-fibrinolysis factors, need to reduce cost of treatment, and desire of lower rate of symptomatic intracranial hemorrhage (SICH). To search for any evidence of such practice, we examined whether lower doses of tPA had comparable efficacy and safety to standard dose in Chinese patients with AIS.…”

mentioning

confidence: 99%

Standard-Dose Intravenous Tissue-Type Plasminogen Activator for Stroke Is Better Than Low Doses

Liao

Wang

Pan

et al. 2014

Background and Purpose-It remains uncertain whether lower dose intravenous tissue-type plasminogen activator (tPA) for stroke is as effective and safe as the standard dose. Methods-We analyzed data from the Thrombolysis Implementation and Monitor of Acute Ischemic Stroke in China (TIMSChina). Patients who were treated within 4.5 hours after symptom onset were included. These patients were divided into 5 groups according to tPA doses given: <0.5, 0.5 to 0.7, 0.7 to 0.85, 0.85 to 0.95, and ≥0.95 mg/kg. Symptomatic intracranial hemorrhage, mortality, and 90-day outcome assessed by modified Rankin scale were analyzed. Results-A total of 919 patients were enrolled. Among them, 9 had <0.5 mg/kg, 75 had 0.5 to 0.7 mg/kg, 131 had 0.