Low-dose versus standard-dose alteplase in acute ischemic stroke in Asian stroke registries: an individual patient data pooling study

Xia Wang, Faculty of Medicine, The George Institute for Global Health, University of New South Wales, Sydney, Australia.
Jingwei Li, Department of Cardiology, People's Liberation Army General Hospital, Beijing, China.
Tom J. Moullaali, Faculty of Medicine, The George Institute for Global Health, University of New South Wales, Sydney, Australia.
Keon-Joo Lee, The Department of Neurology and Cerebrovascular Center, Seoul National University Bundang Hospital, Seongnam-si, Republic of Korea.
Beom Joon Kim, The Department of Neurology and Cerebrovascular Center, Seoul National University Bundang Hospital, Seongnam-si, Republic of Korea.
Hee-Joon Bae, The Department of Neurology and Cerebrovascular Center, Seoul National University Bundang Hospital, Seongnam-si, Republic of Korea.
Anxin Wang, Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
Yilong Wang, Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
David Z. Wang, College of Medicine, University of Illinois, Peoria, IL, USA.Follow
Yongjun Wang, Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
Masaya Kumamoto, Department of Cerebrovascular Medicine, National Cerebral and Cardiovascular Centre, Osaka, Japan.
Kazunori Toyoda, Department of Cerebrovascular Medicine, National Cerebral and Cardiovascular Centre, Osaka, Japan.
Masatoshi Koga, Department of Cerebrovascular Medicine, National Cerebral and Cardiovascular Centre, Osaka, Japan.
Shoichiro Sato, Department of Cerebrovascular Medicine, National Cerebral and Cardiovascular Centre, Osaka, Japan.
Sohei Yoshimura, Department of Cerebrovascular Medicine, National Cerebral and Cardiovascular Centre, Osaka, Japan.
Yi Sui, Shenyang First People's Hospital, Shenyang Medical College Affiliated Shenyang Brain Hospital, Shenyang Brain Institute, Shenyang Clinical Research Center for Neurological Disorders, Shenyang, China.
Bing Xu, Shenyang First People's Hospital, Shenyang Medical College Affiliated Shenyang Brain Hospital, Shenyang Brain Institute, Shenyang Clinical Research Center for Neurological Disorders, Shenyang, China.
Ying Xiao, Shenyang First People's Hospital, Shenyang Medical College Affiliated Shenyang Brain Hospital, Shenyang Brain Institute, Shenyang Clinical Research Center for Neurological Disorders, Shenyang, China.
Tsong-Hai Lee, Department of Neurology, Chang Gung Memorial Hospital, Linkou Medical Center and College of Medicine, Chang Gung University, Taoyuan, Taiwan.
Chia-Wei Liou, Department of Neurology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan.
Jiann-Der Lee, Department of Neurology, Chiayi Chang Gung Memorial Hospital, Chiayi, Taiwan.
Tsung-I Peng, Department of Neurology, Keelung Chang Gung Memorial Hospital, Keelung, Taiwan.
Yen-Chu Huang, Department of Neurology, Chiayi Chang Gung Memorial Hospital, Chiayi, Taiwan.
Prakash R. Paliwal, Division of Neurology, National University Hospital, Singapore.
Manasi Sharma, Division of Neurology, National University Hospital, Singapore.
Cyrus Escabillas, Stroke Services, Department of Neurology, Jose R. Reyes Memorial Medical Center, Manila, Philippines.
Jose C. Navarro, Stroke Services, Department of Neurology, Jose R. Reyes Memorial Medical Center, Manila, Philippines.
Mu-Chien Sun, Department of Neurology, Changhua Christian Hospital, Changhua, Taiwan.
Yi Dong, Department of Neurology, Huashan Hospital Affiliated to Fudan University, Shanghai, China.
Qiang Dong, Department of Neurology, Huashan Hospital Affiliated to Fudan University, Shanghai, China.
Craig S. Anderson, Faculty of Medicine, The George Institute for Global Health, University of New South Wales, Sydney, Australia.

Document Type

Article

Abstract

OBJECTIVE: To investigate the comparative efficacy and safety of the low-dose versus standard-dose alteplase using real-world acute stroke registry data from Asian countries. METHODS: Individual participant data were obtained from nine acute stroke registries from China, Japan, Philippines, Singapore, South Korea, and Taiwan between 2005 and 2018. Inverse probability of treatment weight was used to remove baseline imbalances between those receiving low-dose versus standard-dose alteplase. The primary outcome was death or disability defined by modified Rankin Scale scores of 2 to 6 at 90 days. Secondary outcomes were symptomatic intracerebral hemorrhage and death. Generalized linear mixed models with the individual registry as a random intercept were performed to determine associations of treatment with low-dose alteplase and outcomes. RESULTS: Of the 6250 patients (mean age 66 years, 36% women) included in these analyses, 1610 (24%) were treated with low-dose intravenous alteplase. Clinical outcomes for low-dose alteplase were not significantly different to those for standard-dose alteplase, adjusted odds ratios for death or disability: 1.00 (0.85-1.19) and symptomatic intracerebral hemorrhage 0.87 (0.63-1.19), except for lower death with borderline significance, 0.77 (0.59-1.01). CONCLUSIONS: The present analyses of real-world Asian acute stroke registry data suggest that low-dose intravenous alteplase has overall comparable efficacy for functional recovery and greater potential safety in terms of reduced mortality, to standard-dose alteplase for the treatment of acute ischemic stroke.

Medical Subject Headings

Adult; Aged; Aged, 80 and over; Asia; Asian People; Dose-Response Relationship, Drug; Female; Fibrinolytic Agents (administration & dosage); Humans; Male; Middle Aged; Registries; Stroke (drug therapy); Tissue Plasminogen Activator (administration & dosage)

Publication Date

10-1-2019

Publication Title

International journal of stroke : official journal of the International Stroke Society

E-ISSN

1747-4949

Volume

14

Issue

7

First Page

670

Last Page

677

PubMed ID

31226919

Digital Object Identifier (DOI)

10.1177/1747493019858777

Link to Full Text

Share

COinS