The Japan Statin Treatment Against Recurrent Stroke (J-STARS): A Multicenter, Randomized, Open-label, Parallel-group Study.
BACKGROUND
Although statin therapy is beneficial for the prevention of initial stroke, the benefit for recurrent stroke and its subtypes remains to be determined in Asian, in whom stroke profiles are different from Caucasian. This study examined whether treatment with low-dose pravastatin prevents stroke recurrence in ischemic stroke patients.


METHODS
This is a multicenter, randomized, open-label, blinded-endpoint, parallel-group study of patients who experienced non-cardioembolic ischemic stroke. All patients had a total cholesterol level between 4.65 and 6.21 mmol/L at enrollment, without the use of statins. The pravastatin group patients received 10 mg of pravastatin/day; the control group patients received no statins. The primary endpoint was the occurrence of stroke and transient ischemic attack (TIA), with the onset of each stroke subtype set to be one of the secondary endpoints.


RESULTS
Although 3000 patients were targeted, 1578 patients (491 female, age 66.2 years) were recruited and randomly assigned to pravastatin group or control group. During the follow-up of 4.9 ± 1.4 years, although total stroke and TIA similarly occurred in both groups (2.56 vs. 2.65%/year), onset of atherothrombotic infarction was less frequent in pravastatin group (0.21 vs. 0.64%/year, p = 0.0047, adjusted hazard ratio 0.33 [95%CI 0.15 to 0.74]). No significant intergroup difference was found for the onset of other stroke subtypes, and for the occurrence of adverse events.


CONCLUSIONS
Although whether low-dose pravastatin prevents recurrence of total stroke or TIA still needs to be examined in Asian, this study has generated a hypothesis that it may reduce occurrence of stroke due to larger artery atherosclerosis.


BACKGROUND
This study was initially supported by a grant from the Ministry of Health, Labour and Welfare, Japan. After the governmental support expired, it was conducted in collaboration between Hiroshima University and the Foundation for Biomedical Research and Innovation.
Department of Clinical Neuroscience and Therapeutics, Hiroshima University Graduate School of Biomedical and Health Sciences, Hiroshima, Japan.
Naohisa
N
Hosomi
Foundation for Biomedical Research and Innovation Translational Research Informatics Center, Kobe, Japan.
Yoji
Y
Nagai
Hiroshima City Rehabilitation Hospital, Hiroshima, Japan.
Tatsuo
T
Kohriyama
Stroke Center, Kinki University, Osakasayama, Japan.
Toshiho
T
Ohtsuki
Department of Clinical Neuroscience and Therapeutics, Hiroshima University Graduate School of Biomedical and Health Sciences, Hiroshima, Japan.
Shiro
S
Aoki
Department of Clinical Neuroscience and Therapeutics, Hiroshima University Graduate School of Biomedical and Health Sciences, Hiroshima, Japan.
Tomohisa
T
Nezu
Department of Clinical Neuroscience and Therapeutics, Hiroshima University Graduate School of Biomedical and Health Sciences, Hiroshima, Japan.
Hirofumi
H
Maruyama
Department of Neurological Surgery, Matsuyama Shimin Hospital, Matsuyama, Japan.
Norio
N
Sunami
National Cerebral and Cardiovascular Center, Suita, Japan.
Chiaki
C
Yokota
Department of Neurology, Tokyo Women's Medical University School of Medicine, Tokyo, Japan.
Kazuo
K
Kitagawa
Department of Neurology, Iwate Medical University, Morioka, Japan.
Yasuo
Y
Terayama
Department of Neurology, Tokyo Saiseikai Central Hospital, Tokyo, Japan.
Makoto
M
Takagi
Seiai Rehabilitation Hospital, Fukuoka, Japan.
Setsuro
S
Ibayashi
National Cerebral and Cardiovascular Center, Suita, Japan.
Masakazu
M
Nakamura
Division of Biostatistics and Clinical Epidemiology, University of Toyama Graduate School of Medicine and Pharmaceutical Sciences, Toyama, Japan.
Hideki
H
Origasa
Foundation for Biomedical Research and Innovation Translational Research Informatics Center, Kobe, Japan.
Masanori
M
Fukushima
Department of Behavioral Neurology and Cognitive Neuroscience, Tohoku University Graduate School of Medicine, Sendai, Japan.
Etsuro
E
Mori
National Cerebral and Cardiovascular Center, Suita, Japan.
Kazuo
K
Minematsu
Clinical Research Center, International University of Health and Welfare, Center for Brain and Cerebral Vessels, Sanno Hospital and Sanno Medical Center, Tokyo, Japan.
Shinichiro
S
Uchiyama
Federation of National Public Service Personnel Mutual Aid Associations Tachikawa Hospital, Tokyo, Japan.
Yukito
Y
Shinohara
National Cerebral and Cardiovascular Center, Suita, Japan.
Takenori
T
Yamaguchi
Department of Clinical Neuroscience and Therapeutics, Hiroshima University Graduate School of Biomedical and Health Sciences, Hiroshima, Japan.
Masayasu
M
Matsumoto
D000368:Aged; D044466:Asian People; D002545:Brain Ischemia / Q000150:complications; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D007564:Japan; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D017063:Outcome Assessment, Health Care / Q000379:methods / Q000706:statistics & numerical data; D017035:Pravastatin / Q000627:therapeutic use*; D016016:Proportional Hazards Models; D012008:Recurrence; D020521:Stroke / Q000188:drug therapy* / Q000208:ethnology* / Q000209:etiology
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D017035:Pravastatin
Atherothrombotic infarction; Cholesterol; Hemorrhagic stroke; Ischemic stroke; Statin