Kazuo Kitagawa1, Naohisa Hosomi2, Yoji Nagai3, Tatsuo Kagimura4, Toshiho Ohtsuki5, Hideki Origasa6, Kazuo Minematsu7, Shinichiro Uchiyama8, Masakazu Nakamura7, Masayasu Matsumoto2. 1. Department of Neurology, Tokyo Women's Medical University. 2. Department of Clinical Neuroscience and Therapeutics, Hiroshima University Graduate School of Biomedical and Health Sciences. 3. Center for Clinical Research, Kobe University Hospital. 4. Foundation for Biomedical Research and Innovation, Translational Research Informatics Center. 5. Stroke Center, Kindai University Hospital. 6. Division of Biostatistics and Clinical Epidemiology, University of Toyama Graduate School of Medicine and Pharmaceutical Sciences. 7. National Cerebral and Cardiovascular Center. 8. Clinical Research Center, International University of Health and Welfare, Center for Brain and Cerebral Vessels, Sanno Hospital and Sanno Medical Center.
Abstract
AIMS: The pleiotropic effects of statins on recurrent stroke remain unclear. We investigated the effects of pravastatin on high-sensitivity C-reactive proteins (Hs-CRP) in ischemic stroke, and explored the impact of Hs-CRP on recurrent stroke and vascular events. METHODS: This randomized open-label trial was ancillary to the J-STARS trial. One thousand and ninety-five patients with non-cardiogenic ischemic stroke were assigned to the pravastatin (n=545) or control groups (n=550). The primary and secondary endpoints were serum Hs-CRP reduction and stroke recurrence, including both ischemic and hemorrhagic ones, respectively. Onset of vascular events and each stroke subtype in relation to Hs-CRP levels were also determined. RESULTS: In the pravastatin treatment group, Hs-CRP levels (median 711 µg/L, IQR 344-1500) significantly decreased 2 months later (median 592 µg/L, IQR 301-1390), and they remained significantly lower until the end of the study. However, in the control group, baseline Hs-CRP levels were similar to those 2 months later. The reduction of Hs-CRP levels from the baseline to 2 months in the pravastatin group was statistically significant compared with the control (p=0.007). One SD increase in log-transformed Hs-CRP increased the risk of stroke recurrence (HR 1.17, 95% CI 0.97-1.40) and vascular events (HR 1.30, 95% CI 1.12-1.51). With an Hs-CRP cut-off of 1000 µg/L, higher Hs-CRP significantly increased the risk of recurrent stroke (HR 1.50, 95% CI 1.03-2.17)and vascular events (HR 1.68, 95% CI 1.23-2.29). CONCLUSION: In non-cardiogenic ischemic stroke, pravastatin treatment may reduce vascular inflammation as assessed by Hs-CRP, and higher Hs-CRP levels appeared to increase the risk of recurrent stroke and vascular events.
RCT Entities:
AIMS: The pleiotropic effects of statins on recurrent stroke remain unclear. We investigated the effects of pravastatin on high-sensitivity C-reactive proteins (Hs-CRP) in ischemic stroke, and explored the impact of Hs-CRP on recurrent stroke and vascular events. METHODS: This randomized open-label trial was ancillary to the J-STARS trial. One thousand and ninety-five patients with non-cardiogenic ischemic stroke were assigned to the pravastatin (n=545) or control groups (n=550). The primary and secondary endpoints were serum Hs-CRP reduction and stroke recurrence, including both ischemic and hemorrhagic ones, respectively. Onset of vascular events and each stroke subtype in relation to Hs-CRP levels were also determined. RESULTS: In the pravastatin treatment group, Hs-CRP levels (median 711 µg/L, IQR 344-1500) significantly decreased 2 months later (median 592 µg/L, IQR 301-1390), and they remained significantly lower until the end of the study. However, in the control group, baseline Hs-CRP levels were similar to those 2 months later. The reduction of Hs-CRP levels from the baseline to 2 months in the pravastatin group was statistically significant compared with the control (p=0.007). One SD increase in log-transformed Hs-CRP increased the risk of stroke recurrence (HR 1.17, 95% CI 0.97-1.40) and vascular events (HR 1.30, 95% CI 1.12-1.51). With an Hs-CRP cut-off of 1000 µg/L, higher Hs-CRP significantly increased the risk of recurrent stroke (HR 1.50, 95% CI 1.03-2.17)and vascular events (HR 1.68, 95% CI 1.23-2.29). CONCLUSION: In non-cardiogenic ischemic stroke, pravastatin treatment may reduce vascular inflammation as assessed by Hs-CRP, and higher Hs-CRP levels appeared to increase the risk of recurrent stroke and vascular events.
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