title: Final Results of Cilostazol-Aspirin Therapy against Recurrent Stroke with Intracranial Artery Stenosis (CATHARSIS).
abstract: OBJECTIVE
  To compare the effect of cilostazol plus aspirin versus aspirin alone on the progression of intracranial arterial stenosis (IAS), and to compare ischemic and hemorrhagic events in patients with symptomatic IAS, an investigator-driven, nationwide multicenter cooperative randomized controlled trial (CATHARSIS; ClinicalTrials.gov Identifier 00333164) was conducted.
  
  
  METHODS
  165 noncardioembolic ischemic stroke patients with >50% stenosis in the responsible intracranial artery after 2 weeks to 6 months from the onset were randomly allocated to receive either cilostazol 200 mg/day plus aspirin 100 mg/day (n = 83, CA group) or aspirin 100 mg/day alone (n = 82, A group). The primary endpoint was the progression of IAS on magnetic resonance angiography at 2 years after randomization. Secondary endpoints were any vascular events, any cause of death, serious adverse events, new silent brain infarcts, and worsening of the modified Rankin Scale score.
  
  
  RESULTS
  Progression of IAS was observed in 9.6% of the CA group patients and in 5.6% of the A group patients, with no significant intergroup difference (p = 0.53). The incidence of the secondary endpoints tended to be lower in the CA group compared with the A group, although the differences were not significant. By using exploratory logistic regression analysis adjusted for patient background characteristics, it was shown that the risk for certain combinations of secondary endpoints was lower in the CA group than in the A group [all vascular events and silent brain infarcts: odds ratio (OR) = 0.37, p = 0.04; stroke and silent brain infarcts: OR = 0.34, p = 0.04; all vascular events, worsening of modified Rankin Scale scores and silent brain infracts: OR = 0.41, p = 0.03]. Major hemorrhage was observed in 4 patients of the CA group and in 3 of the A group.
  
  
  CONCLUSIONS
  Progression of IAS during the 2-year observation period appears to be less frequent than previously reported in stroke patients on antiplatelet agents after the acute phase, which could be due to the adequate control of risk factors, and because patients with stroke within 2 weeks after the onset were excluded. The results of the CATHARSIS trial suggest a potential utility of pharmacotherapies with cilostazol plus aspirin as well as of strict control of risk factors for the management of symptomatic IAS. Larger studies with higher statistical power are required to obtain conclusive results.
authors.affiliation: Clinical Research Center for Medicine, International University of Health and Welfare, Tokyo, Japan ; Center for Brain and Cerebral Vessels, Sanno Hospital and Sanno Medical Center, Tokyo, Japan.
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Uchiyama
authors.affiliation: Department of Neurosurgery, Kobe City General Hospital, Kobe, Japan.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Sakai
authors.affiliation: Department of Neurology, Tokyo Women's Medical University, Tokyo, Japan.
authors.forename: Sono
authors.initials: S
authors.lastname: Toi
authors.affiliation: Department of Neuroendovascular Therapy, Cerebrovascular Center and Clinical Research Institute, Tohoku University, Sendai, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Ezura
authors.affiliation: National Hospital Organization Kyushu Medical Center, Fukuoka, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Okada
authors.affiliation: Department of Neurology, Saiseikai Central Hospital, Tokyo, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Takagi
authors.affiliation: Translational Research Informatics Center, Kobe, Japan.
authors.forename: Yoji
authors.initials: Y
authors.lastname: Nagai
authors.affiliation: Translational Research Informatics Center, Kobe, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Matsubara
authors.affiliation: National Cerebral and Cardiovascular Research Center, Osaka, Japan.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Minematsu
authors.affiliation: Department of Neurology, Keio University, Tokyo, Japan.
authors.forename: Norihiro
authors.initials: N
authors.lastname: Suzuki
authors.affiliation: International Medical Center, Saitama Medical University, Saitama, Japan.
authors.forename: Norio
authors.initials: N
authors.lastname: Tanahashi
authors.affiliation: Department of Neurosurgery, Mie University, Mie, Japan.
authors.forename: Waro
authors.initials: W
authors.lastname: Taki
authors.affiliation: Kokura Memorial Hospital, Hiroshima University, Hiroshima, Japan.
authors.forename: Izumi
authors.initials: I
authors.lastname: Nagata
authors.affiliation: Department of Clinical Neuroscience and Therapeutics, Hiroshima University, Hiroshima, Japan.
authors.forename: Masayasu
authors.initials: M
authors.lastname: Matsumoto
keywords: Aspirin; Cilostazol; Intracranial arterial stenosis; Stroke prevention