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Published in: Clinical Drug Investigation 3/2010

01-03-2010 | Original Research Article

Does Functional Outcome in Acute Ischaemic Stroke Patients Correlate with the Amount of Free-Radical Scavenger Treatment?

A Retrospective Study of Edaravone Therapy

Authors: Dr Yoshiko Unno, Makiko Katayama, Hideaki Shimizu

Published in: Clinical Drug Investigation | Issue 3/2010

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Abstract

Background: Edaravone is a free-radical scavenger that has been widely used for acute ischaemic stroke in Japan. However, the optimal total dosage of edaravone has not been established.
Objective: To clarify the relationship between the gain in functional recovery (rehabilitation gain) and the total amount of edaravone used for acute-phase therapy for cerebral infarction at a convalescent rehabilitation hospital. We also sought to determine if there were differences in outcome between stroke subtypes.
Methods: Medical records were retrospectively surveyed to identify patients who had received edaravone treatment for acute-phase cerebral infarction at Kawakita General Hospital, Tokyo, Japan, followed by recovery rehabilitation at Kawakita Rehabilitation Hospital, Tokyo, Japan, for ≥30 days. Edaravone was initiated within 24 hours of stroke onset, and was administered as a 30 mg (1 ampoule) continuous intravenous infusion twice daily for up to 14 days. Patients were stratified into tertiles based on the total amount of edaravone used (measured in ampoules) during the acute phase (i.e. administration duration). Rehabilitation gain was defined as the change (increase) from convalescent rehabilitation hospital admission to discharge in the Functional Independence Measure-Motor (ΔFIM-M) or Barthel Index (ΔBI) score.
Results: Of the 72 enrolled patients, 21 belonged to the lower (short-term) tertile (0–14 ampoules), 27 to the middle (medium-term) tertile (15–23 ampoules) and 24 to the upper (long-term) tertile (24–33 ampoules) groups. There was no correlation between the total amount of edaravone used and the length of stay at an acute-phase hospital. However, a significant correlation was seen between the total amount of edaravone used and ΔFIM-M (adjusted regression coefficient 0.81; p = 0.003) and ΔBI (0.88; p = 0.005) score in patients with cardioembolic stroke; no significant correlation was seen in other stroke subtypes. Cardioembolic stroke patients also showed improvements in both FIM-M and BI score as the total amount of edaravone used increased. The difference between the short- and long-term group was 10.1 (95% CI 2.3, 17.8) for ΔFIM-M score, and 12.0 (95% CI 2.8, 21.2) for ΔBI score. Patients with atherothrombotic stroke showed a similar tendency with respect to ΔBI score.
Conclusion: Edaravone dose-dependently increases rehabilitation gain according to ΔFIM-M and ΔBI scores in patients with cardioembolic stroke, and a similar trend was also observed with respect to ΔBI score in patients with atherothrombotic stroke. This suggests that the total amount of edaravone used is associated with its efficacy for rehabilitation gain.
Literature
1.
go back to reference Ministry of Health, Labour and Welfare. Trends in leading causes of death: summary of vital statistics. Tokyo: Statistics and Information Department Minister’s Secretariat Ministry of Health, Labour and Welfare, 2009 Oct 22 Ministry of Health, Labour and Welfare. Trends in leading causes of death: summary of vital statistics. Tokyo: Statistics and Information Department Minister’s Secretariat Ministry of Health, Labour and Welfare, 2009 Oct 22
2.
go back to reference Cerebral Embolism Task Force. Cardiogenic brain embolism. Arch Neurol 1986; 43: 71–84CrossRef Cerebral Embolism Task Force. Cardiogenic brain embolism. Arch Neurol 1986; 43: 71–84CrossRef
3.
go back to reference Wolf PA, Abbott RD, Kannel WB. Atrial fibrillation as an independent risk factor for stroke: the Framingham Study. Stroke 1991; 22: 983–8PubMedCrossRef Wolf PA, Abbott RD, Kannel WB. Atrial fibrillation as an independent risk factor for stroke: the Framingham Study. Stroke 1991; 22: 983–8PubMedCrossRef
4.
go back to reference Yamaguchi T. Intermediate results of the post-marketing survey of rt-PA [in Japanese]. Jpn J Stroke 2008; 30: 760–3CrossRef Yamaguchi T. Intermediate results of the post-marketing survey of rt-PA [in Japanese]. Jpn J Stroke 2008; 30: 760–3CrossRef
5.
go back to reference Tei H. Frequency and its annual change of usage of antithrombotic agent and edarabone according to stroke subtype. Stroke databank [in Japanese]. Tokyo: Nakayama Shoten Company,Limited, 2005: 80–1 Tei H. Frequency and its annual change of usage of antithrombotic agent and edarabone according to stroke subtype. Stroke databank [in Japanese]. Tokyo: Nakayama Shoten Company,Limited, 2005: 80–1
6.
go back to reference Yamamoto Y, Kuwahara T, Wanatabe K, et al. Antioxidant activity of 3-methyl-1-phenyl-2-pyrazolin-5-one. Redox Rep 1996; 2: 333–8 Yamamoto Y, Kuwahara T, Wanatabe K, et al. Antioxidant activity of 3-methyl-1-phenyl-2-pyrazolin-5-one. Redox Rep 1996; 2: 333–8
7.
go back to reference Watanabe T, Morita I, Nishi H, et al. Preventive effect of MCI-186 on 15-HPETE induced vascular endothelial cell injury in vitro. Prostaglandins Leukot Essent Fatty Acids 1988; 33: 81–7PubMedCrossRef Watanabe T, Morita I, Nishi H, et al. Preventive effect of MCI-186 on 15-HPETE induced vascular endothelial cell injury in vitro. Prostaglandins Leukot Essent Fatty Acids 1988; 33: 81–7PubMedCrossRef
8.
go back to reference Abe K, Yuki S, Kogure K. Strong attenuation of ischemic and postischemic brain edema in rats by a novel free radical scavenger. Stroke 1988; 19: 480–5PubMedCrossRef Abe K, Yuki S, Kogure K. Strong attenuation of ischemic and postischemic brain edema in rats by a novel free radical scavenger. Stroke 1988; 19: 480–5PubMedCrossRef
9.
go back to reference Yamamoto T, Yuki S, Watanabe T, et al. Delayed neuronal death prevented by inhibition of increased hydroxyl radical formation in a transient cerebral ischemia. Brain Res 1997; 762: 240–2PubMedCrossRef Yamamoto T, Yuki S, Watanabe T, et al. Delayed neuronal death prevented by inhibition of increased hydroxyl radical formation in a transient cerebral ischemia. Brain Res 1997; 762: 240–2PubMedCrossRef
10.
go back to reference The Edaravone Acute Brain Infarction Study Group. Effect of a novel free radical scavenger, edaravone (MCI-186), on acute brain infarction: randomized, placebo-controlled, double-blind study at multicenters. Cerebrovasc Dis 2003; 15: 222–9CrossRef The Edaravone Acute Brain Infarction Study Group. Effect of a novel free radical scavenger, edaravone (MCI-186), on acute brain infarction: randomized, placebo-controlled, double-blind study at multicenters. Cerebrovasc Dis 2003; 15: 222–9CrossRef
11.
go back to reference Joint Committee on Guidelines for the Management of Stroke. Japanese guidelines for the management of stroke 2009 [in Japanese]. Tokyo: Kyowa Kikaku, 2009 Joint Committee on Guidelines for the Management of Stroke. Japanese guidelines for the management of stroke 2009 [in Japanese]. Tokyo: Kyowa Kikaku, 2009
12.
go back to reference Mitsubishi Tanabe Pharma Corporation. Radicut (edaravone) prescribing information [in Japanese]. Osaka: Mitsubishi Tanabe Pharma Corporation, 2009 Mitsubishi Tanabe Pharma Corporation. Radicut (edaravone) prescribing information [in Japanese]. Osaka: Mitsubishi Tanabe Pharma Corporation, 2009
13.
go back to reference Naritomi H. Research on the influences of muscle atrophy preventive therapy starting from the acute phase of cerebral infarction on chronic phase motor function [in Japanese]. Health Labour Science Research Grant, Comprehensive Research on Aging and Health. 2007 Overview Study Rep 2008. Osaka: Ministry of Health, Labour and Welfare of Japan, 2008 Naritomi H. Research on the influences of muscle atrophy preventive therapy starting from the acute phase of cerebral infarction on chronic phase motor function [in Japanese]. Health Labour Science Research Grant, Comprehensive Research on Aging and Health. 2007 Overview Study Rep 2008. Osaka: Ministry of Health, Labour and Welfare of Japan, 2008
14.
go back to reference Kageyama M, Toriyama S, Tsuboshita A, et al. A postmarketing drug use survey of a neuroprotective drug Radicut injection 30 mg (nonproprietary name: edaravone) for acute ischemic stroke [in Japanese]. J New Rem Clin 2009; 58: 1212–26 Kageyama M, Toriyama S, Tsuboshita A, et al. A postmarketing drug use survey of a neuroprotective drug Radicut injection 30 mg (nonproprietary name: edaravone) for acute ischemic stroke [in Japanese]. J New Rem Clin 2009; 58: 1212–26
15.
go back to reference Okamura S, Kobayashi R, Sakamaki T. Case-mix payment in Japanese medical care. Health Policy 2005; 74: 282–6PubMedCrossRef Okamura S, Kobayashi R, Sakamaki T. Case-mix payment in Japanese medical care. Health Policy 2005; 74: 282–6PubMedCrossRef
16.
go back to reference Yasunaga H, Ide H, Imamura T, et al. Influence of Japan’s new diagnosis procedure combination-based payment system on the surgical sector: does it really shorten the hospital stay? Surg Today 2006; 36: 577–85PubMedCrossRef Yasunaga H, Ide H, Imamura T, et al. Influence of Japan’s new diagnosis procedure combination-based payment system on the surgical sector: does it really shorten the hospital stay? Surg Today 2006; 36: 577–85PubMedCrossRef
17.
go back to reference Muranaga F, Kumamoto I, Uto Y, et al. Development of hospital data warehouse for cost analysis of DPC based on medical costs. Methods Inf Med 2007; 46: 679–85PubMed Muranaga F, Kumamoto I, Uto Y, et al. Development of hospital data warehouse for cost analysis of DPC based on medical costs. Methods Inf Med 2007; 46: 679–85PubMed
18.
go back to reference Fushimi K, Hashimoto H, Imanaka Y, et al. Functional mapping of hospitals by diagnosis-dominant case-mix analysis. BMC Health Serv Res 2007; 7: 50PubMedCrossRef Fushimi K, Hashimoto H, Imanaka Y, et al. Functional mapping of hospitals by diagnosis-dominant case-mix analysis. BMC Health Serv Res 2007; 7: 50PubMedCrossRef
19.
go back to reference Adams HP, Bendixen BH, Kappelle LJ, et al. Classification of subtype of acute ischemic stroke definitions for use in a multicenter clinical trial. Stroke 1993; 24: 35–41PubMedCrossRef Adams HP, Bendixen BH, Kappelle LJ, et al. Classification of subtype of acute ischemic stroke definitions for use in a multicenter clinical trial. Stroke 1993; 24: 35–41PubMedCrossRef
20.
go back to reference Keith RA, Granger CV, Hamilton BB, et al. The functional independence measure: a new tool for rehabilitation. Adv Clin Rehabil 1987; 1: 6–18PubMed Keith RA, Granger CV, Hamilton BB, et al. The functional independence measure: a new tool for rehabilitation. Adv Clin Rehabil 1987; 1: 6–18PubMed
21.
go back to reference Mahoney FI, Barthel DW. Functional evaluation: the Barthel Index. Maryland State Med J 1965 Feb; 14: 61–5 Mahoney FI, Barthel DW. Functional evaluation: the Barthel Index. Maryland State Med J 1965 Feb; 14: 61–5
22.
go back to reference Ueno Y, Zhang N, Miyamoto N, et al. Edaravone attenuates white matter lesions through endothelial protection in a rat chronic hypoperfusion model. Neuroscience 2009; 162: 317–27PubMedCrossRef Ueno Y, Zhang N, Miyamoto N, et al. Edaravone attenuates white matter lesions through endothelial protection in a rat chronic hypoperfusion model. Neuroscience 2009; 162: 317–27PubMedCrossRef
23.
go back to reference Shinohara Y, Saito I, Kobayashi S, et al. Edaravone (radical scavenger) versus sodium ozagrel (antiplatelet Agent) in acute noncardioembolic ischemic stroke (EDO Trial). Cerebrovasc Dis 2009; 27: 485–92PubMedCrossRef Shinohara Y, Saito I, Kobayashi S, et al. Edaravone (radical scavenger) versus sodium ozagrel (antiplatelet Agent) in acute noncardioembolic ischemic stroke (EDO Trial). Cerebrovasc Dis 2009; 27: 485–92PubMedCrossRef
24.
go back to reference Kikuchi K, Tancharoen S, Matsuda F, et al. Edaravone attenuates cerebral ischemic injury by suppressing aquaporin-4. Biochem Biophys Res Commun 2009; 390: 1121–5PubMedCrossRef Kikuchi K, Tancharoen S, Matsuda F, et al. Edaravone attenuates cerebral ischemic injury by suppressing aquaporin-4. Biochem Biophys Res Commun 2009; 390: 1121–5PubMedCrossRef
25.
go back to reference Toyoda K, Fujii K, Kamouchi M, et al. Free radical scavenger, edaravone, in stroke with internal carotid artery occlusion. J Neurol Sci 2004 Jun 15; 221(1-2): 11–7PubMedCrossRef Toyoda K, Fujii K, Kamouchi M, et al. Free radical scavenger, edaravone, in stroke with internal carotid artery occlusion. J Neurol Sci 2004 Jun 15; 221(1-2): 11–7PubMedCrossRef
26.
go back to reference Yamaguchi S, Takahashi K, Kobayashi S. Thrombolytic therapy and cerebroprotecting drug (edaravone) coadministration therapy: stroke databank [in Japanese]. Tokyo: Nakayama Shoten Company, Limited, 2005: 98–9 Yamaguchi S, Takahashi K, Kobayashi S. Thrombolytic therapy and cerebroprotecting drug (edaravone) coadministration therapy: stroke databank [in Japanese]. Tokyo: Nakayama Shoten Company, Limited, 2005: 98–9
27.
go back to reference Yamada K, Yoshikawa Y, Nishimura S, et al. Do anti-thrombotic drug and edaravone combined therapies serve to decrease the frequency of progressive lacuna infarction? Jpn J Stroke 2007; 28: 652–4CrossRef Yamada K, Yoshikawa Y, Nishimura S, et al. Do anti-thrombotic drug and edaravone combined therapies serve to decrease the frequency of progressive lacuna infarction? Jpn J Stroke 2007; 28: 652–4CrossRef
28.
go back to reference Mishina M, Komaba Y, Kobayashi S, et al. Efficacy of edaravone, a free radical scavenger, for the treatment of acute lacunar infarction. Neurol Med Chir (Tokyo) 2005; 45(7): 344–8CrossRef Mishina M, Komaba Y, Kobayashi S, et al. Efficacy of edaravone, a free radical scavenger, for the treatment of acute lacunar infarction. Neurol Med Chir (Tokyo) 2005; 45(7): 344–8CrossRef
29.
go back to reference Matsumoto S, Horio S, Matayoshi S, et al. Therapy of acute cerebral infarction influencing convalescent rehabilitation: focusing on cerebroprotective drug, edaravone [abstract]. Jpn J Rehab Med 2005; 42(6): 429 Matsumoto S, Horio S, Matayoshi S, et al. Therapy of acute cerebral infarction influencing convalescent rehabilitation: focusing on cerebroprotective drug, edaravone [abstract]. Jpn J Rehab Med 2005; 42(6): 429
30.
go back to reference Goto F. Official announcement of Japan Stroke Scale. Jpn J Stroke 1997; 19: 1–5CrossRef Goto F. Official announcement of Japan Stroke Scale. Jpn J Stroke 1997; 19: 1–5CrossRef
31.
go back to reference Lyden P, Brott T, Tilley B, et al. Improved reliability of the NIH Stroke Scale using video training. NINDS TPA Stroke Study Group. Stroke 1994; 25: 2220–6 Lyden P, Brott T, Tilley B, et al. Improved reliability of the NIH Stroke Scale using video training. NINDS TPA Stroke Study Group. Stroke 1994; 25: 2220–6
32.
go back to reference van Swieten JC, Koudstaal PJ, Visser MC, et al. Interobserver agreement for the assessment of handicap in stroke patients. Stroke 1988; 19: 604–7PubMedCrossRef van Swieten JC, Koudstaal PJ, Visser MC, et al. Interobserver agreement for the assessment of handicap in stroke patients. Stroke 1988; 19: 604–7PubMedCrossRef
33.
go back to reference Wang PY, Kao CH, Mui MY, et al. Leukocyte infiltration in acute hemispheric ischemic stroke. Stroke 1993; 24: 236–40PubMedCrossRef Wang PY, Kao CH, Mui MY, et al. Leukocyte infiltration in acute hemispheric ischemic stroke. Stroke 1993; 24: 236–40PubMedCrossRef
34.
go back to reference Kawase T, Mizukami M, Tazawa T, et al. Dynamic pathophysiology of cerebral infarction and revascularization. I: ischemic cerebral edema [in Japanese]. No To Shinkei 1982; 34: 1077–83PubMed Kawase T, Mizukami M, Tazawa T, et al. Dynamic pathophysiology of cerebral infarction and revascularization. I: ischemic cerebral edema [in Japanese]. No To Shinkei 1982; 34: 1077–83PubMed
35.
go back to reference Lodder J, Krijne-Kubat B, van der Lugt PJ. Timing of autopsy-confirmed hemorrhagic infarction with reference to cardio-embolic stroke. Stroke 1988; 19: 1482–4PubMedCrossRef Lodder J, Krijne-Kubat B, van der Lugt PJ. Timing of autopsy-confirmed hemorrhagic infarction with reference to cardio-embolic stroke. Stroke 1988; 19: 1482–4PubMedCrossRef
36.
go back to reference Suzuki K. Pathology of cardioembolic stroke [in Japanese]. Ther Res 2000; 3: 403–8 Suzuki K. Pathology of cardioembolic stroke [in Japanese]. Ther Res 2000; 3: 403–8
37.
go back to reference Houkin K, Ueno K, Tada M, et al. Arterial recanalization in acute stage of cerebral infarction [in Japanese]. Neurol Med Chir (Tokyo) 1987; 27: 295–301CrossRef Houkin K, Ueno K, Tada M, et al. Arterial recanalization in acute stage of cerebral infarction [in Japanese]. Neurol Med Chir (Tokyo) 1987; 27: 295–301CrossRef
38.
go back to reference Peters O, Back T, Lindauer U, et al. Increased formation of reactive oxygen species after permanent and reversible middle cerebral artery occlusion in the rat. J Cereb Blood Flow Metab 1998; 18: 196–205PubMedCrossRef Peters O, Back T, Lindauer U, et al. Increased formation of reactive oxygen species after permanent and reversible middle cerebral artery occlusion in the rat. J Cereb Blood Flow Metab 1998; 18: 196–205PubMedCrossRef
39.
go back to reference Furuya D, Tanahashi N, Araki N, et al. Edaravone therapy initiated immediately after cardioembolic stroke and its effects on functional recovery. Jpn J Stroke 2006; 28: 291–6CrossRef Furuya D, Tanahashi N, Araki N, et al. Edaravone therapy initiated immediately after cardioembolic stroke and its effects on functional recovery. Jpn J Stroke 2006; 28: 291–6CrossRef
40.
go back to reference Yamamoto Y, Ohara T, Hamanaka M, et al. Predictive factors for progressive motor deficits in penetrating artery infarctions in two different arterial territories. J Neurol Sci 2010 Jan 15; 288: 170–4PubMedCrossRef Yamamoto Y, Ohara T, Hamanaka M, et al. Predictive factors for progressive motor deficits in penetrating artery infarctions in two different arterial territories. J Neurol Sci 2010 Jan 15; 288: 170–4PubMedCrossRef
41.
go back to reference Clavier I, Hommel M, Besson G, et al. Long-term prognosis of symptomatic lacunar infarcts: a hospital-based study. Stroke 1994; 25: 2005–9PubMedCrossRef Clavier I, Hommel M, Besson G, et al. Long-term prognosis of symptomatic lacunar infarcts: a hospital-based study. Stroke 1994; 25: 2005–9PubMedCrossRef
42.
go back to reference Samuelsson M, Söderfeldt B, Olsson GB. Functional outcome in patients with lacunar infarction. Stroke 1996; 27: 842–6PubMedCrossRef Samuelsson M, Söderfeldt B, Olsson GB. Functional outcome in patients with lacunar infarction. Stroke 1996; 27: 842–6PubMedCrossRef
43.
go back to reference Hassaballa H, Gorelick PB, West CP, et al. Ischemic stroke outcome: racial differences in the trial of danaparoid in acute stroke (TOAST). Neurology 2001; 57: 691–7PubMedCrossRef Hassaballa H, Gorelick PB, West CP, et al. Ischemic stroke outcome: racial differences in the trial of danaparoid in acute stroke (TOAST). Neurology 2001; 57: 691–7PubMedCrossRef
44.
go back to reference Uno M, Kitazato K, Suzue A, et al. Inhibition of brain damage by edaravone, a free radical scavenger, can be monitored by plasma biomarkers that detect oxidative and astrocyte damage in patients with acute cerebral infarction. Free Radical Biol Med 2005; 39: 1109–16CrossRef Uno M, Kitazato K, Suzue A, et al. Inhibition of brain damage by edaravone, a free radical scavenger, can be monitored by plasma biomarkers that detect oxidative and astrocyte damage in patients with acute cerebral infarction. Free Radical Biol Med 2005; 39: 1109–16CrossRef
45.
go back to reference Inouye M. Predicting models of outcome stratified by age after first stroke rehabilitation in Japan. Am J Phys Med Rehabil 2001; 8: 586–91CrossRef Inouye M. Predicting models of outcome stratified by age after first stroke rehabilitation in Japan. Am J Phys Med Rehabil 2001; 8: 586–91CrossRef
46.
go back to reference Musicco M, Emberti L, Nappi G, et al. Early and long-term outcome of rehabilitation in stroke patients: the role of patient characteristics, time of initiation, and duration of interventions. Arch Phys Med Rehabil 2003; 84: 551–8PubMedCrossRef Musicco M, Emberti L, Nappi G, et al. Early and long-term outcome of rehabilitation in stroke patients: the role of patient characteristics, time of initiation, and duration of interventions. Arch Phys Med Rehabil 2003; 84: 551–8PubMedCrossRef
47.
go back to reference Ng YS, Stein J, Salles SS, et al. Clinical characteristics and rehabilitation outcomes of patients with posteriar cerebral artery stroke. Arch Phys Med Rehabil 2005; 86: 2138–43PubMedCrossRef Ng YS, Stein J, Salles SS, et al. Clinical characteristics and rehabilitation outcomes of patients with posteriar cerebral artery stroke. Arch Phys Med Rehabil 2005; 86: 2138–43PubMedCrossRef
48.
go back to reference Ergreletzis D, Kevorkian CG, Rintala D. Rehabilitation of the older stroke patient: functional outcome and comparison with younger patients. Am J Phys Med Rehabil 2002; 81: 881–9CrossRef Ergreletzis D, Kevorkian CG, Rintala D. Rehabilitation of the older stroke patient: functional outcome and comparison with younger patients. Am J Phys Med Rehabil 2002; 81: 881–9CrossRef
Metadata
Title
Does Functional Outcome in Acute Ischaemic Stroke Patients Correlate with the Amount of Free-Radical Scavenger Treatment?
A Retrospective Study of Edaravone Therapy
Authors
Dr Yoshiko Unno
Makiko Katayama
Hideaki Shimizu
Publication date
01-03-2010
Publisher
Springer International Publishing
Published in
Clinical Drug Investigation / Issue 3/2010
Print ISSN: 1173-2563
Electronic ISSN: 1179-1918
DOI
https://doi.org/10.2165/11535500-000000000-00000

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