Cilostazol Versus Aspirin on White Matter Changes in Cerebral Small Vessel Disease: A Randomized Controlled Trial

Byeong C. Kim; Young Chul Youn; Jee Hyang Jeong; Hyun Jeong Han; Jong Hun Kim; Jae Hong Lee; Kee Hyung Park; Kyung Won Park; Eun Joo Kim; Mi Sun Oh; Yongsoo Shim; Jong Min Lee; Yong Ho Choi; Gilsoon Park; Sohui Kim; Hyun Young Park; Bora Yoon; Soo Jin Yoon; Soo Jin Cho; Key Chung Park; Duk L. Na; Sun Ah Park; Seong Hye Choi

doi:10.1161/STROKEAHA.121.035766

Cilostazol Versus Aspirin on White Matter Changes in Cerebral Small Vessel Disease: A Randomized Controlled Trial

Byeong C. Kim, Young Chul Youn, Jee Hyang Jeong, Hyun Jeong Han, Jong Hun Kim, Jae Hong Lee, Kee Hyung Park, Kyung Won Park, Eun Joo Kim, Mi Sun Oh, Yongsoo Shim, Jong Min Lee, Yong Ho Choi, Gilsoon Park, Sohui Kim, Hyun Young Park, Bora Yoon, Soo Jin Yoon, Soo Jin Cho, Key Chung ParkDuk L. Na, Sun Ah Park, Seong Hye Choi

Department of Neurology

Research output: Contribution to journal › Article › peer-review

9 Scopus citations

Abstract

Background and Purpose: Cerebral small vessel disease is characterized by progressive cerebral white matter changes (WMCs). This study aimed to compare the effects of cilostazol and aspirin on changes in WMC volume in patients with cerebral small vessel disease. Methods: In a multicenter, double-blind, randomized controlled trial, participants with moderate or severe WMCs and at least one lacunar infarction detected on brain magnetic resonance imaging were randomly assigned to the cilostazol and aspirin groups in a 1:1 ratio. Cilostazol slow release (200 mg) or aspirin (100 mg) capsules were administered once daily for 2 years. The primary outcome was the change in WMC volume on magnetic resonance images from baseline to 2 years. Secondary imaging outcomes include changes in the number of lacunes or cerebral microbleeds, fractional anisotropy, and mean diffusivity on diffusion tensor images, and brain atrophy. Secondary clinical outcomes include all ischemic strokes, all ischemic vascular events, and changes in cognition, motor function, mood, urinary symptoms, and disability. Results: Between July 2013 and August 2016, 256 participants were randomly assigned to the cilostazol (n=127) and aspirin (n=129) groups. Over 2 years, the percentage of WMC volume to total WM volume and the percentage of WMC volume to intracranial volume increased in both groups, but neither analysis showed significant differences between the groups. The peak height of the mean diffusivity histogram in normal-appearing WMs was significantly reduced in the aspirin group compared with the cilostazol group. Cilostazol significantly reduced the risk of ischemic vascular event compared with aspirin (0.5 versus 4.5 cases per 100 person-years; hazard ratio, 0.11 [95% CI, 0.02-0.89]). Conclusions: There was no significant difference between the effects of cilostazol and aspirin on WMC progression in patients with cerebral small vessel disease. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01932203.

Original language	English
Pages (from-to)	698-709
Number of pages	12
Journal	Stroke
Volume	29
Issue number	2
DOIs	https://doi.org/10.1161/STROKEAHA.121.035766
State	Published - 1 Mar 2022

Bibliographical note

Funding Information:
This study was funded by the Korea Otsuka Pharmaceutical Company. The funder of the study had no role in the study’s design, data collection, analysis, interpretation of data, writing of the report, or decision to submit the paper for publication.

Publisher Copyright:
© 2022 Lippincott Williams and Wilkins. All rights reserved.

Keywords

cerebral small vessel disease
cilostazol
clinical trial
white matter

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10.1161/STROKEAHA.121.035766

Cite this

Kim, B. C., Youn, Y. C., Jeong, J. H., Han, H. J., Kim, J. H., Lee, J. H., Park, K. H., Park, K. W., Kim, E. J., Oh, M. S., Shim, Y., Lee, J. M., Choi, Y. H., Park, G., Kim, S., Park, H. Y., Yoon, B., Yoon, S. J., Cho, S. J., ... Choi, S. H. (2022). Cilostazol Versus Aspirin on White Matter Changes in Cerebral Small Vessel Disease: A Randomized Controlled Trial. Stroke, 29(2), 698-709. https://doi.org/10.1161/STROKEAHA.121.035766

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title = "Cilostazol Versus Aspirin on White Matter Changes in Cerebral Small Vessel Disease: A Randomized Controlled Trial",

abstract = "Background and Purpose: Cerebral small vessel disease is characterized by progressive cerebral white matter changes (WMCs). This study aimed to compare the effects of cilostazol and aspirin on changes in WMC volume in patients with cerebral small vessel disease. Methods: In a multicenter, double-blind, randomized controlled trial, participants with moderate or severe WMCs and at least one lacunar infarction detected on brain magnetic resonance imaging were randomly assigned to the cilostazol and aspirin groups in a 1:1 ratio. Cilostazol slow release (200 mg) or aspirin (100 mg) capsules were administered once daily for 2 years. The primary outcome was the change in WMC volume on magnetic resonance images from baseline to 2 years. Secondary imaging outcomes include changes in the number of lacunes or cerebral microbleeds, fractional anisotropy, and mean diffusivity on diffusion tensor images, and brain atrophy. Secondary clinical outcomes include all ischemic strokes, all ischemic vascular events, and changes in cognition, motor function, mood, urinary symptoms, and disability. Results: Between July 2013 and August 2016, 256 participants were randomly assigned to the cilostazol (n=127) and aspirin (n=129) groups. Over 2 years, the percentage of WMC volume to total WM volume and the percentage of WMC volume to intracranial volume increased in both groups, but neither analysis showed significant differences between the groups. The peak height of the mean diffusivity histogram in normal-appearing WMs was significantly reduced in the aspirin group compared with the cilostazol group. Cilostazol significantly reduced the risk of ischemic vascular event compared with aspirin (0.5 versus 4.5 cases per 100 person-years; hazard ratio, 0.11 [95% CI, 0.02-0.89]). Conclusions: There was no significant difference between the effects of cilostazol and aspirin on WMC progression in patients with cerebral small vessel disease. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01932203.",

keywords = "cerebral small vessel disease, cilostazol, clinical trial, white matter",

author = "Kim, {Byeong C.} and Youn, {Young Chul} and Jeong, {Jee Hyang} and Han, {Hyun Jeong} and Kim, {Jong Hun} and Lee, {Jae Hong} and Park, {Kee Hyung} and Park, {Kyung Won} and Kim, {Eun Joo} and Oh, {Mi Sun} and Yongsoo Shim and Lee, {Jong Min} and Choi, {Yong Ho} and Gilsoon Park and Sohui Kim and Park, {Hyun Young} and Bora Yoon and Yoon, {Soo Jin} and Cho, {Soo Jin} and Park, {Key Chung} and Na, {Duk L.} and Park, {Sun Ah} and Choi, {Seong Hye}",

note = "Funding Information: This study was funded by the Korea Otsuka Pharmaceutical Company. The funder of the study had no role in the study{\textquoteright}s design, data collection, analysis, interpretation of data, writing of the report, or decision to submit the paper for publication. Publisher Copyright: {\textcopyright} 2022 Lippincott Williams and Wilkins. All rights reserved.",

year = "2022",

month = mar,

day = "1",

doi = "10.1161/STROKEAHA.121.035766",

language = "English",

volume = "29",

pages = "698--709",

journal = "Stroke",

issn = "0039-2499",

publisher = "Lippincott Williams and Wilkins Ltd.",

number = "2",

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Kim, BC, Youn, YC, Jeong, JH, Han, HJ, Kim, JH, Lee, JH, Park, KH, Park, KW, Kim, EJ, Oh, MS, Shim, Y, Lee, JM, Choi, YH, Park, G, Kim, S, Park, HY, Yoon, B, Yoon, SJ, Cho, SJ, Park, KC, Na, DL, Park, SA & Choi, SH 2022, 'Cilostazol Versus Aspirin on White Matter Changes in Cerebral Small Vessel Disease: A Randomized Controlled Trial', Stroke, vol. 29, no. 2, pp. 698-709. https://doi.org/10.1161/STROKEAHA.121.035766

TY - JOUR

T1 - Cilostazol Versus Aspirin on White Matter Changes in Cerebral Small Vessel Disease

T2 - A Randomized Controlled Trial

AU - Kim, Byeong C.

AU - Youn, Young Chul

AU - Jeong, Jee Hyang

AU - Han, Hyun Jeong

AU - Kim, Jong Hun

AU - Lee, Jae Hong

AU - Park, Kee Hyung

AU - Park, Kyung Won

AU - Kim, Eun Joo

AU - Oh, Mi Sun

AU - Shim, Yongsoo

AU - Lee, Jong Min

AU - Choi, Yong Ho

AU - Park, Gilsoon

AU - Kim, Sohui

AU - Park, Hyun Young

AU - Yoon, Bora

AU - Yoon, Soo Jin

AU - Cho, Soo Jin

AU - Park, Key Chung

AU - Na, Duk L.

AU - Park, Sun Ah

AU - Choi, Seong Hye

N1 - Funding Information: This study was funded by the Korea Otsuka Pharmaceutical Company. The funder of the study had no role in the study’s design, data collection, analysis, interpretation of data, writing of the report, or decision to submit the paper for publication. Publisher Copyright: © 2022 Lippincott Williams and Wilkins. All rights reserved.

PY - 2022/3/1

Y1 - 2022/3/1

N2 - Background and Purpose: Cerebral small vessel disease is characterized by progressive cerebral white matter changes (WMCs). This study aimed to compare the effects of cilostazol and aspirin on changes in WMC volume in patients with cerebral small vessel disease. Methods: In a multicenter, double-blind, randomized controlled trial, participants with moderate or severe WMCs and at least one lacunar infarction detected on brain magnetic resonance imaging were randomly assigned to the cilostazol and aspirin groups in a 1:1 ratio. Cilostazol slow release (200 mg) or aspirin (100 mg) capsules were administered once daily for 2 years. The primary outcome was the change in WMC volume on magnetic resonance images from baseline to 2 years. Secondary imaging outcomes include changes in the number of lacunes or cerebral microbleeds, fractional anisotropy, and mean diffusivity on diffusion tensor images, and brain atrophy. Secondary clinical outcomes include all ischemic strokes, all ischemic vascular events, and changes in cognition, motor function, mood, urinary symptoms, and disability. Results: Between July 2013 and August 2016, 256 participants were randomly assigned to the cilostazol (n=127) and aspirin (n=129) groups. Over 2 years, the percentage of WMC volume to total WM volume and the percentage of WMC volume to intracranial volume increased in both groups, but neither analysis showed significant differences between the groups. The peak height of the mean diffusivity histogram in normal-appearing WMs was significantly reduced in the aspirin group compared with the cilostazol group. Cilostazol significantly reduced the risk of ischemic vascular event compared with aspirin (0.5 versus 4.5 cases per 100 person-years; hazard ratio, 0.11 [95% CI, 0.02-0.89]). Conclusions: There was no significant difference between the effects of cilostazol and aspirin on WMC progression in patients with cerebral small vessel disease. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01932203.

AB - Background and Purpose: Cerebral small vessel disease is characterized by progressive cerebral white matter changes (WMCs). This study aimed to compare the effects of cilostazol and aspirin on changes in WMC volume in patients with cerebral small vessel disease. Methods: In a multicenter, double-blind, randomized controlled trial, participants with moderate or severe WMCs and at least one lacunar infarction detected on brain magnetic resonance imaging were randomly assigned to the cilostazol and aspirin groups in a 1:1 ratio. Cilostazol slow release (200 mg) or aspirin (100 mg) capsules were administered once daily for 2 years. The primary outcome was the change in WMC volume on magnetic resonance images from baseline to 2 years. Secondary imaging outcomes include changes in the number of lacunes or cerebral microbleeds, fractional anisotropy, and mean diffusivity on diffusion tensor images, and brain atrophy. Secondary clinical outcomes include all ischemic strokes, all ischemic vascular events, and changes in cognition, motor function, mood, urinary symptoms, and disability. Results: Between July 2013 and August 2016, 256 participants were randomly assigned to the cilostazol (n=127) and aspirin (n=129) groups. Over 2 years, the percentage of WMC volume to total WM volume and the percentage of WMC volume to intracranial volume increased in both groups, but neither analysis showed significant differences between the groups. The peak height of the mean diffusivity histogram in normal-appearing WMs was significantly reduced in the aspirin group compared with the cilostazol group. Cilostazol significantly reduced the risk of ischemic vascular event compared with aspirin (0.5 versus 4.5 cases per 100 person-years; hazard ratio, 0.11 [95% CI, 0.02-0.89]). Conclusions: There was no significant difference between the effects of cilostazol and aspirin on WMC progression in patients with cerebral small vessel disease. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01932203.

KW - cerebral small vessel disease

KW - cilostazol

KW - clinical trial

KW - white matter

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U2 - 10.1161/STROKEAHA.121.035766

DO - 10.1161/STROKEAHA.121.035766

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AN - SCOPUS:85125553367

SN - 0039-2499

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JO - Stroke

JF - Stroke

IS - 2

ER -

Cilostazol Versus Aspirin on White Matter Changes in Cerebral Small Vessel Disease: A Randomized Controlled Trial

Abstract

Bibliographical note

Keywords

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