The Japan Statin Treatment Against Recurrent Stroke (J-STARS): A Multicenter, Randomized, Open-label, Parallel-group Study
Naohisa Hosomi,
Yoji Nagai,
Tatsuo Kohriyama,
Toshiho Ohtsuki,
Shiro Aoki,
Tomohisa Nezu,
Hirofumi Maruyama,
Norio Sunami,
Chiaki Yokota,
Kazuo Kitagawa,
Yasuo Terayama,
Makoto Takagi,
Setsuro Ibayashi,
Masakazu Nakamura,
Hideki Origasa,
Masanori Fukushima,
Etsuro Mori,
Kazuo Minematsu,
Shinichiro Uchiyama,
Yukito Shinohara,
Takenori Yamaguchi,
Masayasu Matsumoto
Affiliations
Naohisa Hosomi
Department of Clinical Neuroscience and Therapeutics, Hiroshima University Graduate School of Biomedical and Health Sciences, Hiroshima, Japan
Yoji Nagai
Foundation for Biomedical Research and Innovation Translational Research Informatics Center, Kobe, Japan
Tatsuo Kohriyama
Hiroshima City Rehabilitation Hospital, Hiroshima, Japan
Toshiho Ohtsuki
Stroke Center, Kinki University, Osakasayama, Japan
Shiro Aoki
Department of Clinical Neuroscience and Therapeutics, Hiroshima University Graduate School of Biomedical and Health Sciences, Hiroshima, Japan
Tomohisa Nezu
Department of Clinical Neuroscience and Therapeutics, Hiroshima University Graduate School of Biomedical and Health Sciences, Hiroshima, Japan
Hirofumi Maruyama
Department of Clinical Neuroscience and Therapeutics, Hiroshima University Graduate School of Biomedical and Health Sciences, Hiroshima, Japan
Norio Sunami
Department of Neurological Surgery, Matsuyama Shimin Hospital, Matsuyama, Japan
Chiaki Yokota
National Cerebral and Cardiovascular Center, Suita, Japan
Kazuo Kitagawa
Department of Neurology, Tokyo Women's Medical University School of Medicine, Tokyo, Japan
Yasuo Terayama
Department of Neurology, Iwate Medical University, Morioka, Japan
Makoto Takagi
Department of Neurology, Tokyo Saiseikai Central Hospital, Tokyo, Japan
Setsuro Ibayashi
Seiai Rehabilitation Hospital, Fukuoka, Japan
Masakazu Nakamura
National Cerebral and Cardiovascular Center, Suita, Japan
Hideki Origasa
Division of Biostatistics and Clinical Epidemiology, University of Toyama Graduate School of Medicine and Pharmaceutical Sciences, Toyama, Japan
Masanori Fukushima
Foundation for Biomedical Research and Innovation Translational Research Informatics Center, Kobe, Japan
Etsuro Mori
Department of Behavioral Neurology and Cognitive Neuroscience, Tohoku University Graduate School of Medicine, Sendai, Japan
Kazuo Minematsu
National Cerebral and Cardiovascular Center, Suita, Japan
Shinichiro Uchiyama
Clinical Research Center, International University of Health and Welfare, Center for Brain and Cerebral Vessels, Sanno Hospital and Sanno Medical Center, Tokyo, Japan
Yukito Shinohara
Federation of National Public Service Personnel Mutual Aid Associations Tachikawa Hospital, Tokyo, Japan
Takenori Yamaguchi
National Cerebral and Cardiovascular Center, Suita, Japan
Masayasu Matsumoto
Department of Clinical Neuroscience and Therapeutics, Hiroshima University Graduate School of Biomedical and Health Sciences, Hiroshima, Japan
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. Finding: 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. Interpretation: 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. Funding: 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.
