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. Registration- URL: https://www.clinicaltrials.gov. Unique identifier: NCT01013532.