Current status of intravenous tissue plasminogen activator dosage for acute ischaemic stroke: an updated systematic review

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

The optimal dose of recombinant tissue plasminogen activator (rtPA) for acute ischaemic stroke (AIS) remains controversial, especially in Asian countries. We aimed to update the evidence regarding the use of low-dose versus standard-dose rtPA. We performed a systematic literature search across MEDLINE, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), PsycINFO and Cumulative Index to Nursing and Allied Health Literature (CINAHL) from inception to 22 August 2016 to identify all related studies. The outcomes were death or disability (defined by modified Rankin Scale 2–6), death, and symptomatic intracerebral haemorrhage (sICH). Where possible, data were pooled for meta-analysis with ORs and corresponding 95% CIs by means of random-effects or fixed-effects meta-analysis. We included 26 observational studies and 1 randomised controlled trial with a total of 23 210 patients. Variable doses of rtPA were used for thrombolysis of AIS in Asia. Meta-analysis shows that low-dose rtPA was not associated with increased risk of death or disability (OR 1.13, 95% CI 0.95 to 1.33), or death (OR 0.86, 95% CI 0.74 to 1.01), or decreased risk of sICH (OR 1.06, 95% CI 0.65 to 1.72). The results remained consistent when sensitivity analyses were performed including only low-dose and standard-dose rtPA or only Asian studies. Our review shows small difference between the outcomes or the risk profile in the studies using low-dose and/or standard-dose rtPA for AIS. Low-dose rtPA was not associated with lower risk of death or disability, death alone, or sICH.

Related collections

Most cited references 34

Record: found
Abstract: found
Article: not found

Alteplase at 0.6 mg/kg for acute ischemic stroke within 3 hours of onset: Japan Alteplase Clinical Trial (J-ACT).

Kazuo Hashi, Etsuro Mori, Yukito Shinohara … (2006)

Based on previous studies comparing different recombinant tissue plasminogen activator (rt-PA) doses, we performed a clinical trial with 0.6 mg/kg, which is lower than the internationally approved dosage of 0.9 mg/kg, aiming to assess the efficacy and safety of alteplase in acute ischemic stroke for the Japanese. Our prospective, multicenter, single-arm, open-label trial was designed with a target sample size of 100 patients. The primary end points were the proportion of patients with a modified Rankin Scale (mRS) score of 0 to 1 at 3 months and the incidence of symptomatic intracranial hemorrhage (sICH) within 36 hours. Thresholds for these end points were determined by calculating 90% CIs of weighted averages derived from published reports. The protocol was defined according to the National Institute of Neurological Disorders and Stroke (NINDS) rt-PA stroke study with slight modifications. Among the 103 patients enrolled, 38 had an mRS of 0 to 1 at 3 months; this proportion (36.9%) exceeded the predetermined threshold of 33.9%. sICH within 36 hours occurred in 6 patients; this incidence (5.8%) was lower than the threshold of 9.6%. In patients receiving 0.6 mg/kg alteplase, the outcome and the incidence of sICH were comparable to published data for 0.9 mg/kg. These findings indicate that alteplase, when administered at 0.6 mg/kg to Japanese patients, might offer a clinical efficacy and safety that are compatible with data reported in North America and the European Union for a 0.9 mg/kg dose.

0 comments Cited 112 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Effects of 0.6 mg/kg intravenous alteplase on vascular and clinical outcomes in middle cerebral artery occlusion: Japan Alteplase Clinical Trial II (J-ACT II).

Etsuro Mori, Jyoji Nakagawara, Teruyuki Hirano … (2010)

The purpose of this study was to evaluate further the efficacy of 0.6 mg/kg intravenous alteplase on vascular and clinical outcomes in patients with middle cerebral artery occlusion in a postmarketing Phase IV trial of prospective cohort study design. Alteplase was given intravenously at 0.6 mg/kg to patients with ischemic stroke within 3 hours of onset with MR angiography-documented middle cerebral artery occlusion. Vascular outcome was evaluated by MR angiography at 6 and 24 hours after symptom onset based on the modified Mori grade. The primary end points also included a favorable outcome (modified Rankin Scale 0 to 1 at 3 months after onset) and incidence of symptomatic intracranial hemorrhage within 36 hours after treatment. The impact of recanalization on clinical outcome was assessed by stepwise logistic regression analysis. Fifty-eight patients were enrolled. Recanalization was noted in 51.7% on 6-hour MR angiography and 69.0% on 24-hour MR angiography. A favorable clinical outcome was achieved in 46.6%. None had symptomatic intracranial hemorrhage. In logistic regression models, recanalization on either 6-hour or 24-hour MR angiography was an independent predictor for clinical outcome as well as the baseline National Institutes of Health Stroke Scale score. Early recanalization of an occluded middle cerebral artery can be provoked by 0.6 mg/kg intravenous alteplase and may induce a favorable clinical outcome. The rates of recanalization and favorable outcome are comparable to that previously reported with the 0.9-mg/kg dose.

0 comments Cited 47 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Outcomes of thrombolytic therapy for acute ischemic stroke in Chinese patients: the Taiwan Thrombolytic Therapy for Acute Ischemic Stroke (TTT-AIS) study.

Chih-Ping Chung, Pang-Hung Hsu, Giia-Sheun Peng … (2010)

The safety and efficacy of alteplase for ischemic stroke has not been examined in Chinese patients. We assessed the safety and efficacy of alteplase for acute ischemic stroke in daily clinical practice in Taiwan. A prospective, multicenter, observational study was conducted in Taiwan from December 2004 to July 2008. Eligible patients (241) receiving alteplase were recruited and divided into 2 groups: standard dose (0.90 + or - 0.02 mg/kg, n=125) and lower dose (0.72 + or - 0.07 mg/kg, n=116). Primary outcome measures were safety: symptomatic intracerebral hemorrhage and death within 3 months. The secondary outcome measure was efficacy a modified Rankin scale of 0 to 2 after 3 months. The standard-dose group had higher rates of symptomatic intracerebral hemorrhage using National Institute of Neurological Diseases and Stroke, European Cooperative Acute Stroke Study, and Safe Implementation of Thrombolysis in Stroke-Monitoring Study definitions (10.4% versus 5.2%, 8.0% versus 2.6%, and 5.6% versus 1.7%, respectively) and mortality within 3 months (12.8% versus 6.9%), twice that of the lower-dose group. This pattern was more prominent in older patients. Significantly higher rates of symptomatic intracerebral hemorrhage per European Cooperative Acute Stroke Study (15.4% versus 3.3%, P=0.0257) and mortality (21.1% versus 5.0%, P=0.0099) and significantly lower independence rate (32.6% versus 53.6%, P=0.0311) were observed among patients > or = 70 years old receiving the standard dose than those receiving the lower dose. This study suggests that the standard dose of 0.9 mg/kg alteplase may not be optimal for treating aged Chinese patients. However, the dose of recombinant tissue plasminogen activator for ischemic stroke in Chinese patients should be based on more broad and convincing evidences and randomized trials of lower versus higher doses are needed.

0 comments Cited 44 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Journal

Journal ID (nlm-ta): Stroke Vasc Neurol

Journal ID (iso-abbrev): Stroke Vasc Neurol

Journal ID (hwp): svnbmj

Journal ID (publisher-id): svn

Title: Stroke and Vascular Neurology

Publisher: BMJ Publishing Group (BMA House, Tavistock Square, London, WC1H 9JR )

ISSN (Electronic): 2059-8696

Publication date Collection: March 2018

Publication date (Electronic): 13 January 2018

Volume: 3

Issue: 1

Pages: 28-33

Affiliations

[1 ] The George Institute for Global Health , Newtown, New South Wales, Australia

[2 ] departmentSydney Medical School , The University of Sydney , Sydney, New South Wales, Australia

[3 ] departmentDepartment of Neurology , The Second Affiliated Hospital of Soochow University , Suzhou, China

[4 ] departmentDepartment of Cerebrovascular Medicine , National Cerebral and Cardiovascular Center , Osaka, Japan

[5 ] departmentDepartment of Neurology , The First Affiliated Hospital of Chengdu Medical College , Chengdu, China

[6 ] Royal Prince Alfred Hospital , Camperdown, New South Wales, Australia

[7 ] The George Institute China, Peking University Health Science Center , Beijing, China

[8 ] departmentDepartment of Neurology , Oslo University Hospital , Oslo, Norway

[9 ] departmentDepartment of Cardiovascular Sciences and NIHR Biomedical Research Unit for Cardiovascular Diseases , University of Leicester , Leicester, UK

[10 ] departmentYong Loo Lin School of Medicine , National University of Singapore , Singapore

[11 ] departmentDivision of Neurology , National University Hospital , Singapore

Author notes

[Correspondence to ] Dr Jie Yang; yangjie1126@ 123456163.com

Article

Publisher ID: svn-2017-000112

DOI: 10.1136/svn-2017-000112

PMC ID: 5870642

PubMed ID: 29600005

SO-VID: df53a2bb-6533-44f8-9986-123148e8839e

License:

This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/

History

Date received : 27 August 2017

Date revision received : 17 November 2017

Date accepted : 20 November 2017

Funding

Funded by: Department of Science and Technology of Jiangsu Province;

Funded by: FundRef http://dx.doi.org/10.13039/501100001809, National Natural Science Foundation of China;

Custom metadata

special-feature unlocked

Keywords: acute ischemic stroke,asian,low-dose tissue plasminogen activator,thrombolysis

Data availability:

Keywords: acute ischemic stroke, asian, low-dose tissue plasminogen activator, thrombolysis

Current status of intravenous tissue plasminogen activator dosage for acute ischaemic stroke: an updated systematic review

Read this article at

Abstract

Related collections

Asian Journal of Behavioural Studies (AjBeS)

Most cited references 34

Alteplase at 0.6 mg/kg for acute ischemic stroke within 3 hours of onset: Japan Alteplase Clinical Trial (J-ACT).

Effects of 0.6 mg/kg intravenous alteplase on vascular and clinical outcomes in middle cerebral artery occlusion: Japan Alteplase Clinical Trial II (J-ACT II).

Outcomes of thrombolytic therapy for acute ischemic stroke in Chinese patients: the Taiwan Thrombolytic Therapy for Acute Ischemic Stroke (TTT-AIS) study.

Author and article information

Journal

Affiliations

Author notes

Article

History

Funding

Categories

Custom metadata

Comments

Comment on this article

Similar content 164

Cited by 5

Most referenced authors 1,659