Document Type : Original Article
Authors
- Elyar Sadeghi-Hokmabadi 1
- Abdoreza Ghoreishi 2
- Reza Rikhtegar 3
- Payam Sariaslani 4
- Shahram Rafie 5
- Alireza Vakilian 6
- Ehsan Sharifipour 7
- Masoud Mehrpour 8
- Mohammad Saadatnia 9
- Mohammad Mirza-Aghazadeh-Attari 10
- Mehdi Farhoudi 1
1 Neurosciences Research Center AND Division of Neurology, Imam Reza Hospital, Tabriz University of Medical Sciences, Tabriz, Iran
2 Stroke Research Group, Vali-e-Asr Hospital AND Department of Neurology and Stroke Unit, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran
3 Institute of Diagnostic and Interventional Radiology and Neuroradiology, School of Medicine, Essen University Hospital, Germany
4 Clinical Research Development Center, Imam Reza Hospital, Kermanshah University of Medical Sciences, Kermanshah, Iran
5 Department of Neurology, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
6 Department of Neurology, School of Medicine, Rafsanjan University of Medical Sciences, Rafsanjan, Iran Non-Communicable Diseases Research Center, Rafsanjan University of Medical Sciences, Rafsanjan, Iran
7 Neuroscience Research Center, Qom University of Medical Sciences, Qom, Iran
8 Iranian Stroke Association, Shahid Beheshti University of Medical Sciences, Tehran, Iran
9 Isfahan Neurosciences Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
10 Medical Imaging Research Group, Tabriz University of Medical Sciences, Tabriz, Iran
Abstract
Background: Rates of intracranial hemorrhage (ICH) after intravenous thrombolysis (IVT) differ depending on ethnicity, one reason that few Eastern countries have approved a lower dose of alteplase. Data in this regard are scarce in the Middle Eastern region.
Methods: The present retrospective study was performed on data extracted from the Safe Implementation of Treatments in Stroke (SITS) registry. Computed tomography (CT) image analysis was based on the SITS-Monitoring Study (SITS-MOST) definition for symptomatic ICH (SICH). Functional outcome at 3 months was assessed using the modified Rankin Scale (mRS). Multivariate logistic regression including adjusted analysis was used for comparison between groups.
Results: Of 6615 patients, 1055 were enrolled. A total of 86% (n = 906) received a standard dose and 14% (n = 149) received a low dose of alteplase. Favorable 3-month outcome was achieved in 481 (53%) patients in the standard group and 71 (48%) patients in the low-dose group [adjusted odds ratio (AOR) = 1.24, 95% confidence interval (CI): 0.87-1.75, P = 0.218]. SICH occurred in 14 (1.5%) patients in the standard group and 3 (2%) patients in the low-dose group [odds ratio (OR) = 2.77, 95% CI: 0.36-21.04, P = 0.120]. At 3 months, mortality occurred in 145 (16.0%) patients in the standard group and 29 (19.4%) patients in the low-dose group (OR = 1.22, 95% CI: 0.78-1.91, P = 0.346).
Conclusion: Low-dose compared to standard-dose alteplase for patients with acute ischemic stroke (AIS) was not associated with fewer hemorrhagic events and there was no significant difference in the favorable 3-month outcome (mRS: 0-2) or mortality rate.
Keywords
- Kleindorfer D, Broderick J, Demaerschalk B, Saver J. Cost of alteplase has more than doubled over the past decade. Stroke 2017; 48(7): 2000-2.
- Yamaguchi T, Mori E, Minematsu K, Nakagawara J, Hashi K, Saito I, et al. Alteplase at 0.6 mg/kg for acute ischemic stroke within 3 hours of onset: Japan Alteplase Clinical Trial (J-ACT). Stroke 2006; 37(7): 1810-5.
- Hong KS, Ko SB, Yu KH, Jung C, Park SQ, Kim BM, et al. Update of the Korean Clinical Practice Guidelines for Endovascular recanalization therapy in patients with acute ischemic stroke.
J Stroke 2016; 18(1): 102-13. - Anderson CS, Woodward M, Chalmers J. More on low-dose versus standard-dose intravenous alteplase in acute ischemic stroke. N Engl J Med 2018; 378(15):
1465-6. - Sila C. Finding the right t-PA dose for asians with acute ischemic stroke. N Engl J Med 2016; 374(24): 2389-90.
- Dong Y, Cao W, Cheng X, Fang K, Wu F, Yang L, et al. Low-dose intravenous tissue plasminogen activator for acute ischaemic stroke: An alternative or a new standard? Stroke Vasc Neurol 2016; 1(3): 115-21.
- van Asch CJ, Luitse MJ, Rinkel GJ, van dT, I, Algra A, Klijn CJ. Incidence, case fatality, and functional outcome of intracerebral haemorrhage over time, according to age, sex, and ethnic origin: A systematic review and meta-analysis. Lancet Neurol 2010; 9(2): 167-76.
- Koennecke HC, Nohr R, Leistner S, Marx P. Intravenous tPA for ischemic stroke team performance over time, safety, and efficacy in a single-center, 2-year experience. Stroke 2001; 32(5): 1074-8.
- Wahlgren N, Ahmed N, Davalos A, Ford GA, Grond M, Hacke W, et al. Thrombolysis with alteplase for acute ischaemic stroke in the Safe Implementation of Thrombolysis in Stroke-Monitoring Study (SITS-MOST): An observational study. Lancet 2007; 369(9558): 275-82.
- Nakagawara J, Minematsu K, Okada Y, Tanahashi N, Nagahiro S, Mori E, et al. Thrombolysis with 0.6 mg/kg intravenous alteplase for acute ischemic stroke in routine clinical practice: The Japan post-Marketing Alteplase Registration Study (J-MARS). Stroke 2010; 41(9): 1984-9.
- Mori E, Minematsu K, Nakagawara J, Yamaguchi T, Sasaki M, Hirano T. 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). Stroke 2010; 41(3): 461-5.
- Wang X, Robinson TG, Lee TH, Li Q, Arima H, Bath PM, et al. Low-dose vs standard-dose alteplase for patients with acute ischemic stroke: Secondary analysis of the ENCHANTED Randomized Clinical Trial. JAMA Neurol 2017; 74(11): 1328-35.
- Cheng JW, Zhang XJ, Cheng LS, Li GY, Zhang LJ, Ji KX, et al. Low-dose tissue plasminogen activator in acute ischemic stroke: A systematic review and meta-analysis. J Stroke Cerebrovasc Dis 2018; 27(2): 381-90.
- Sharma VK, Kawnayn G, Sarkar N. Acute ischemic stroke: Comparison of low-dose and standard-dose regimes of tissue plasminogen activator. Expert Rev Neurother 2013; 13(8): 895-902.
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