Final results of cilostazol-aspirin therapy against recurrent stroke with intracranial artery stenosis (CATHARSIS)

Shinichiro Uchiyama, Nobuyuki Sakai, Sono Toi, Masayuki Ezura, Yasushi Okada, Makoto Takagi, Yoji Nagai, Yoshihiro Matsubara, Kazuo Minematsu, Norihiro Suzuki, Norio Tanahashi, Waro Taki, Izumi Nagata, Masayasu Matsumoto

Research output: Contribution to journalArticle

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Abstract

Purpose: 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. Conclusion: 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.

Original languageEnglish
Pages (from-to)1-13
Number of pages13
JournalCerebrovascular Diseases Extra
Volume5
Issue number1
DOIs
Publication statusPublished - 2015

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Aspirin
Pathologic Constriction
Arteries
Stroke
Blood Vessels
Therapeutics
Odds Ratio
Brain
cilostazol
Magnetic Resonance Angiography
Platelet Aggregation Inhibitors
Risk Management
Random Allocation
Cause of Death
Randomized Controlled Trials
Logistic Models
Regression Analysis
Research Personnel
Observation
Hemorrhage

Keywords

  • Aspirin
  • Cilostazol
  • Intracranial arterial stenosis
  • Stroke prevention

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Clinical Neurology
  • Neurology

Cite this

Final results of cilostazol-aspirin therapy against recurrent stroke with intracranial artery stenosis (CATHARSIS). / Uchiyama, Shinichiro; Sakai, Nobuyuki; Toi, Sono; Ezura, Masayuki; Okada, Yasushi; Takagi, Makoto; Nagai, Yoji; Matsubara, Yoshihiro; Minematsu, Kazuo; Suzuki, Norihiro; Tanahashi, Norio; Taki, Waro; Nagata, Izumi; Matsumoto, Masayasu.

In: Cerebrovascular Diseases Extra, Vol. 5, No. 1, 2015, p. 1-13.

Research output: Contribution to journalArticle

Uchiyama, S, Sakai, N, Toi, S, Ezura, M, Okada, Y, Takagi, M, Nagai, Y, Matsubara, Y, Minematsu, K, Suzuki, N, Tanahashi, N, Taki, W, Nagata, I & Matsumoto, M 2015, 'Final results of cilostazol-aspirin therapy against recurrent stroke with intracranial artery stenosis (CATHARSIS)', Cerebrovascular Diseases Extra, vol. 5, no. 1, pp. 1-13. https://doi.org/10.1159/000369610
Uchiyama, Shinichiro ; Sakai, Nobuyuki ; Toi, Sono ; Ezura, Masayuki ; Okada, Yasushi ; Takagi, Makoto ; Nagai, Yoji ; Matsubara, Yoshihiro ; Minematsu, Kazuo ; Suzuki, Norihiro ; Tanahashi, Norio ; Taki, Waro ; Nagata, Izumi ; Matsumoto, Masayasu. / Final results of cilostazol-aspirin therapy against recurrent stroke with intracranial artery stenosis (CATHARSIS). In: Cerebrovascular Diseases Extra. 2015 ; Vol. 5, No. 1. pp. 1-13.
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AU - Uchiyama, Shinichiro

AU - Sakai, Nobuyuki

AU - Toi, Sono

AU - Ezura, Masayuki

AU - Okada, Yasushi

AU - Takagi, Makoto

AU - Nagai, Yoji

AU - Matsubara, Yoshihiro

AU - Minematsu, Kazuo

AU - Suzuki, Norihiro

AU - Tanahashi, Norio

AU - Taki, Waro

AU - Nagata, Izumi

AU - Matsumoto, Masayasu

PY - 2015

Y1 - 2015

N2 - Purpose: 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. Conclusion: 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.

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KW - Aspirin

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