Cilostazol versus aspirin in ischemic stroke patients with high-risk cerebral hemorrhage subgroup analysis of the PICASSO trial

Bum Joon Kim, Sun U. Kwon, Joung Ho Park, Yong Jae Kim, Keun Sik Hong, Lawrence K.S. Wong, Sungwook Yu, Yang Ha Hwang, Ji Sung Lee, Juneyoung Lee, Jong Ho Rha, Sung Hyuk Heo, Seong Hwan Ahn, Woo Keun Seo, Jong Moo Park, Ju Hun Lee, Jee Hyun Kwon, Sung Il Sohn, Jin Man Jung, Jose C. NavarroHahn Young Kim, Eung Gyu Kim, Seongheon Kim, Jae Kwan Cha, Man Seok Park, Hyo Suk Nam, Dong Wha Kang

Research output: Contribution to journalArticle

Abstract

Background and Purpose—Although cilostazol has shown less hemorrhagic events than aspirin, only marginal difference was observed in hemorrhagic stroke events among patients at high risk for cerebral hemorrhage. To identify patients who would most benefit from cilostazol, this study analyzed interactions between treatment and subgroups of the PICASSO trial (Prevention of Cardiovascular Events in Asian Ischemic Stroke Patients With High Risk of Cerebral Hemorrhage). Methods—Ischemic stroke patients with a previous intracerebral hemorrhage or multiple microbleeds were randomized to treatment with cilostazol or aspirin and followed up for a mean 1.8 years. Efficacy, defined as the composite of any stroke, myocardial infarction, and vascular death, and safety, defined as the incidence of hemorrhagic stroke, were analyzed in the 2 groups. Interactions between treatment and age, sex, presence of hypertension and diabetes mellitus, index of high-risk cerebral hemorrhage, and white matter lesion burden were analyzed for primary and key secondary outcomes. Changes in vital signs and laboratory results were compared in the 2 groups. Results—Among all 1534 patients enrolled, a significant interaction between treatment group and index of high risk for cerebral hemorrhage on hemorrhagic stroke (P for interaction, 0.03) was observed. Hemorrhagic stroke was less frequent in the cilostazol than in the aspirin group in patients with multiple microbleeds (1 versus 13 events; hazard ratio, 0.08 [95% CI, 0.01–0.61]; P=0.01). A marginal interaction between treatment group and white matter change on any stroke (P for interaction, 0.08) was observed. Cilostazol reduced any stroke significantly in patients with mild (5 versus 16 events; hazard ratio, 0.36 [95% CI, 0.13–0.97]; P=0.04)-to-moderate (16 versus 32 events; hazard ratio, 0.50 [95% CI, 0.29–0.92]; P=0.03) white matter changes. Heart rate and HDL (high-density lipoprotein) cholesterol level were significantly higher in the cilostazol group than in the aspirin group at follow-up. Conclusions—Cilostazol may be more beneficial for ischemic stroke patients with multiple cerebral microbleeds and before white matter changes are extensive.

Original languageEnglish
Pages (from-to)931-937
Number of pages7
JournalStroke
DOIs
Publication statusAccepted/In press - 2020 Jan 1

Keywords

  • Cerebral hemorrhage
  • Diabetes mellitus
  • Follow-up studies
  • Heart rate
  • White matter

ASJC Scopus subject areas

  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine
  • Advanced and Specialised Nursing

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    Kim, B. J., Kwon, S. U., Park, J. H., Kim, Y. J., Hong, K. S., Wong, L. K. S., Yu, S., Hwang, Y. H., Lee, J. S., Lee, J., Rha, J. H., Heo, S. H., Ahn, S. H., Seo, W. K., Park, J. M., Lee, J. H., Kwon, J. H., Sohn, S. I., Jung, J. M., ... Kang, D. W. (Accepted/In press). Cilostazol versus aspirin in ischemic stroke patients with high-risk cerebral hemorrhage subgroup analysis of the PICASSO trial. Stroke, 931-937. https://doi.org/10.1161/STROKEAHA.119.023855