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

Chao, A-Ching; Liu, Ching-Kuan; Chen, Chih‐Hung; Lin, Hongbo; Liu, Chung‐Hsiang; Jeng, Jiann‐Shing; Hu, Chaur‐Jong; Chung, Chih‐Ping; Hsu, Hung‐Yi; Sheng, Wen‐Yung; Hu, Han‐Hwa

doi:10.1161/strokeaha.114.005245

Cited by 54 publications

(75 citation statements)

References 27 publications

(15 reference statements)

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“…Patients who provided blood samples for D-dimer level measurement after the initiation of rt-PA within 24 h after stroke onset were included. In our hospital, the therapeutic window of rt-PA was up to 4.5 h and the dose of rt-PA varied from 0.6 to 0.9 mg/kg depending on age [10] .…”

Section: Study Subjectsmentioning

confidence: 99%

High Plasma D-Dimer Indicates Unfavorable Outcome of Acute Ischemic Stroke Patients Receiving Intravenous Thrombolysis

et al. 2016

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Background: D-dimer is a fibrin degradation product and a possible marker of thromboembolic events. The aim of this study was to investigate the relationship between D-dimer levels and outcome in acute ischemic stroke (AIS) patients receiving intravenous thrombolysis. Methods: This retrospective study included AIS patients who received intravenous thrombolysis with recombinant tissue plasminogen activator (rt-PA) and provided plasma D-dimer level within 24 h after stroke onset during 2009 and 2014 at a single medical center. Unfavorable outcome was defined as modified Rankin scale ≥3 at 3 months after stroke. Symptomatic intracerebral hemorrhage (ICH) was defined as a deterioration of at least 4 points on the National Institutes of Health Stroke Scale within 36 h post thrombolysis. Results: Of 347 patients receiving intravenous rt-PA, 159 (mean age 67.6 ± 13.1 year, 59.7% male) fulfilled the inclusion criteria. In univariate analysis, patients with unfavorable outcome (n = 79) had significantly higher levels of D-dimer than those with favorable outcome (median ln D-dimer = 1.4 vs. 0.7 μg/ml, p < 0.001). After adjustment for clinical variables, a higher level of D-dimer remained significantly associated with an unfavorable outcome (OR 1.90, 95% CI 1.27-2.86, p = 0.002) and the occurrence of symptomatic ICH (OR 2.97, 95% CI 1.15-7.70, p = 0.025). Conclusion: The D-dimer level within 24 h after stroke onset can be an early outcome indicator in AIS patients receiving rt-PA therapy.

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Section: Study Subjectsmentioning

confidence: 99%

High Plasma D-Dimer Indicates Unfavorable Outcome of Acute Ischemic Stroke Patients Receiving Intravenous Thrombolysis

et al. 2016

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“…46,47 Additionally, the Taiwan Thrombolytic Therapy for Acute Ischemic Stroke (TTT-AIS) Study Group found the dose of 0.9 mg/kg of r-tPA to be suboptimal in Chinese patients with higher rates of SICH and found that in patients aged 71 to 80, a lower dose of 0.6 mg/kg was associated with better outcome. 44 These findings have not been confirmed through randomized controlled trials. The practice of administering lower doses of r-tPA for select high-risk patients is not followed in the United States.…”

Section: Risk Factors For Sich and Pathophysiologymentioning

confidence: 92%

“…1 There are some who propose the use of lower doses of r-tPA in populations at higher risk of ICH, such as East Asian populations, as a way to decrease the risk of bleeding. 43,44 For example in Japan, 0.6 mg/kg of r-tPA is the only approved dose since 2005 for acute stroke presenting within 3 hours of symptom onset, based on the results of the Japan Alteplase Clinical Trial (J-ACT) 45 and supported by J-ACT2 and the Japan post-Marketing Alteplase Registration Study (JMARS). 46,47 Additionally, the Taiwan Thrombolytic Therapy for Acute Ischemic Stroke (TTT-AIS) Study Group found the dose of 0.9 mg/kg of r-tPA to be suboptimal in Chinese patients with higher rates of SICH and found that in patients aged 71 to 80, a lower dose of 0.6 mg/kg was associated with better outcome.…”

Section: Risk Factors For Sich and Pathophysiologymentioning

confidence: 99%

Management of Postthrombolysis Hemorrhagic and Orolingual Angioedema Complications

O’Carroll

Aguilar

2015

The Neurohospitalist

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Intravenous recombinant tissue plasminogen activator was first approved for the treatment of acute ischemic stroke in the United States in 1996. Thrombolytic therapy has been proven to be effective in acute ischemic stroke treatment and shown to improve long-term functional outcomes. Its use is associated with an increased risk of symptomatic intracerebral hemorrhage as well as orolingual angioedema. Our goal is to outline the management strategies for these postthrombolysis complications.

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“…However, studies to determine the optimal dose of alteplase for Asian patients have produced conflicting findings. A study in Taiwan that included 1,004 patients who were treated with 0.6-0.9 mg/kg alteplase concluded that a lower dose was associated with a better outcome in patients aged 71-80 years 6 . Similarly, a multicentre registry study in South Korea that included 1,526 patients concluded that the effects of 0.6 mg/kg alteplase were comparable to those of 0.9 mg/ kg 7 .…”

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The question of alteplase dose for stroke is not resolved

Aoki

Kimura

2016

Nat Rev Neurol

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Welfare approved the use of the tissue plasminogen activator (tPA) alteplase for acute stroke at a dose of 0.6 mg/ kg within 3 h of onset, a lower dose than the standard of 0.9 mg/kg in Europe and the USA. The approval of this low dose was based on results of the Japan Alteplase Clinical Trial (J-ACT) 1 ; in this trial, the administered dose of 0.6 mg/kg alteplase was selected on the basis of previous studies that showed 0.6 mg/kg to be noninferior to 0.9 mg/kg in Japanese patients. The recently published Enhanced Control of Hypertension and Thrombolysis Stroke Study (ENCHANTED) 2 , however, was not able to confirm that a dose of 0.6 mg/kg is noninferior to a dose of 0.9 mg/kg in Asian and non-Asian participants, raising questions about standard use of 0.6 mg/kg in Asian medical practice.The 1990s saw the publication of three randomized, double-blind trials of the tPA duteplase for embolic stroke in Japanese patients. A pilot study showed that a dose of 20 million international units (MIU) was superior to placebo 3 , and a subsequent randomized, double-blind, dose comparison study showed that a dose of 30 MIU did not further improve recanalization rates but increased the occurrence of massive brain haematoma formation and haemorrhagic transformation 4 . Furthermore, a study of alteplase for myo cardial infarction showed that the dose required for a coronary patency rate of 65-80% in Japanese patients Stroke-Non-European Union World study demonstrated the safety and efficacy of 0.9 mg/kg alteplase in an Asian population 9 .The ENCHANTED study was designed to compare the effects of low-dose (0.6 mg/kg) alteplase with those of standard-dose (0.9 mg/kg) alteplase in patients who were recruited at 111 clinical centres in 13 countries worldwide 2 . The prespecified primary outcome was the combined end point of death or disability at 90 days. Secondary outcomes included sICH, modified Rankin scale (mRS) scores at 90 days, and quality of life at 90 days. Outcomes were analysed with a linear regression model to test the accepted hypothesis that low-dose alteplase is noninferior to standarddose alteplase. To satisfy the hypothesis of noninferiority, the upper confidence interval of the odds ratio needed to be below 1.14 (a value derived from a Cochrane meta-analysis of alteplase trials).The primary outcome occurred in 53.2% of patients in the low-dose group, and in 51.1% in the standard-dose group (OR 1.09, 95% CI 0.95-1.25), a result that -owing to the confidence intervals -did not demonstrate that 0.6 mg/kg alteplase is noninferior to 0.9 mg/kg alteplase. However, low-dose alteplase was noninferior to standard-dose alteplase in the ordinal analysis of mRS scores and quality of life, and standard-dose alteplase was associated with higher risks of major sICH and death. The distribution of mRS scores in the two groups at 90 days indicated that the lower death rate seen with low-dose alteplase was accompanied by a greater degree of mild to moderately severe residual disability among survivors. Importantly, no differences wer...

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

Cited by 54 publications

References 27 publications

High Plasma D-Dimer Indicates Unfavorable Outcome of Acute Ischemic Stroke Patients Receiving Intravenous Thrombolysis

High Plasma D-Dimer Indicates Unfavorable Outcome of Acute Ischemic Stroke Patients Receiving Intravenous Thrombolysis

Management of Postthrombolysis Hemorrhagic and Orolingual Angioedema Complications

The question of alteplase dose for stroke is not resolved

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