TY - JOUR
T1 - Dual Antiplatelet Therapy Using Cilostazol with Aspirin or Clopidogrel Subanalysis of the CSPS.com Trial
AU - Hoshino, Haruhiko
AU - Toyoda, Kazunori
AU - Omae, Katsuhiro
AU - Ishida, Noriyuki
AU - Uchiyama, Shinichiro
AU - Kimura, Kazumi
AU - Sakai, Nobuyuki
AU - Okada, Yasushi
AU - Tanaka, Kortaro
AU - Origasa, Hideki
AU - Naritomi, Hiroaki
AU - Houkin, Kiyohiro
AU - Yamaguchi, Keiji
AU - Isobe, Masanori
AU - Minematsu, Kazuo
AU - Matsumoto, Masayasu
AU - Tominaga, Teiji
AU - Tomimoto, Hidekazu
AU - Terayama, Yasuo
AU - Yasuda, Satoshi
AU - Yamaguchi, Takenori
N1 - Funding Information:
Dr Hoshino reports personal fees from Daiichi-Sankyo and Pfizer outside the submitted work. Dr Toyoda reports personal fees from Daiichi-Sankyo, Bayer, Bristol-Myers-Squibb, Boehringer-Ingelheim, and Takeda, outside the submitted work. Dr Uchiyama reports receiving grant support, honoraria, advisory board fees, and lecture fees from Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, Takeda, Healios, Otsuka, and Sanofi. Dr Kimura received lecture fees from Bristol-Myers Squibb, Boehringer Ingelheim, Bayer, and Daiichi Sankyo and research funding from Boehringer Ingelheim, Daiichi Sankyo, Pfizer, Medtronic, and Teijin Pharma. Dr Sakai reports receiving grant support and lecture fees from Asahi-Intec, Daiichi Sankyo, Medtronic, NeuroVasc, Stryker, and Terumo. Dr Houkin reports receiving honoraria as principle investigator of a clinical trial from Healios. Dr Yamaguchi reports receiving lecture fee from Daiichi Sankyo. Dr Minematsu reports receiving honoraria from Bayer, Bristol-Myers Squibb, CSL Behring, Daiichi Sankyo, EPS Corporation, Fuji Film Pharma, Healios, Mitsubishi Tanabe, Nippon Chemiphar, Otsuka, Pfizer, Sanofi, and Stryker. Dr Terayama reports receiving grant support, consulting fees, and honoraria from Boehringer Ingelheim, Bristol-Myers Squibb, and Daiichi Sankyo. Dr Yasuda reports receiving grant support, lecture fees, and clinical trial fees from Abbott, Bristol-Myers Squibb, Daiichi Sankyo, and Takeda. Dr Yamaguchi reported personal fees from Daiichi-Sankyo and Pfizer outside the submitted work. The other authors report no conflicts.
Funding Information:
CSPS.com (PI: Dr Yamaguchi) was conducted under a trial contract between the consignee, Japan Cardiovascular Research Foundation, and the consignor, Otsuka Pharmaceutical Co, Ltd. Japan Cardiovascular Research Foundation received funding for trial implementation and management from Otsuka Pharmaceutical Co, Ltd. Otsuka Pharmaceutical Co, Ltd, did not directly contribute to trial design, data management, or statistical analysis and did not contribute to any issues on this subanalysis study. Statistical analysis of this article was performed in the Department of Data Science, National Cerebral and Cardiovascular Center (Omae, Ishida). This study was funded mainly by the Japan Agency for Medical Research and Development to Toyoda K (AMED, 20lk0201094h0002, and 20lk0201109h0001).
Publisher Copyright:
© 2021 Lippincott Williams and Wilkins. All rights reserved.
PY - 2021/11/1
Y1 - 2021/11/1
N2 - Background and Purpose: Although dual antiplatelet therapy (DAPT) with aspirin and clopidogrel reduces the recurrence of ischemic stroke while significantly increasing the bleeding events compared with monotherapy, the CSPS.com trial (Cilostazol Stroke Prevention Study combination) showed that DAPT using cilostazol was more effective without the bleeding risk. In the CSPS.com trial, aspirin or clopidogrel was used as the underlying antiplatelet drug. The effectiveness and safety of each combination were examined and clarified. Methods: In the CSPS.com trial, a multicenter, open-label, randomized controlled study, patients with high-risk, noncardioembolic ischemic stroke 8 to 180 days after onset treated with aspirin or clopidogrel alone at the discretion of the physician in charge were recruited. Patients were randomly assigned to receive either monotherapy or DAPT using cilostazol and followed for 0.5 to 3.5 years. The primary efficacy outcome was first recurrence of ischemic stroke. The safety outcome was severe or life-Threatening bleeding. The analysis was based on the underlying antiplatelet agents. Results: A total of 763 patients taking aspirin and 1116 taking clopidogrel were included in the intention-To-Treat analysis. Although the clopidogrel group had more risk factors than the aspirin group, the primary efficacy outcome and safety outcome did not differ significantly between the 2 groups. In the aspirin group, the primary efficacy outcome and safety outcome did not differ significantly between the DAPT group and the aspirin-monotherapy group. In the clopidogrel group, the primary end point occurred at a rate of 2.31 per 100 patient-years in the DAPT group and 5.19 per 100 patient-years in the clopidogrel-monotherapy group (hazard ratio, 0.447 [95% CI, 0.258-0.774]). Safety outcome did not differ significantly between groups (0.51 per 100 patient-years versus 0.71 per 100 patient-years, respectively; hazard ratio, 0.730 [95% CI, 0.206-2.588]). Conclusions: The combination of cilostazol and clopidogrel significantly reduced the recurrence of ischemic stroke without increasing the bleeding risk in noncardioembolic, high-risk patients.
AB - Background and Purpose: Although dual antiplatelet therapy (DAPT) with aspirin and clopidogrel reduces the recurrence of ischemic stroke while significantly increasing the bleeding events compared with monotherapy, the CSPS.com trial (Cilostazol Stroke Prevention Study combination) showed that DAPT using cilostazol was more effective without the bleeding risk. In the CSPS.com trial, aspirin or clopidogrel was used as the underlying antiplatelet drug. The effectiveness and safety of each combination were examined and clarified. Methods: In the CSPS.com trial, a multicenter, open-label, randomized controlled study, patients with high-risk, noncardioembolic ischemic stroke 8 to 180 days after onset treated with aspirin or clopidogrel alone at the discretion of the physician in charge were recruited. Patients were randomly assigned to receive either monotherapy or DAPT using cilostazol and followed for 0.5 to 3.5 years. The primary efficacy outcome was first recurrence of ischemic stroke. The safety outcome was severe or life-Threatening bleeding. The analysis was based on the underlying antiplatelet agents. Results: A total of 763 patients taking aspirin and 1116 taking clopidogrel were included in the intention-To-Treat analysis. Although the clopidogrel group had more risk factors than the aspirin group, the primary efficacy outcome and safety outcome did not differ significantly between the 2 groups. In the aspirin group, the primary efficacy outcome and safety outcome did not differ significantly between the DAPT group and the aspirin-monotherapy group. In the clopidogrel group, the primary end point occurred at a rate of 2.31 per 100 patient-years in the DAPT group and 5.19 per 100 patient-years in the clopidogrel-monotherapy group (hazard ratio, 0.447 [95% CI, 0.258-0.774]). Safety outcome did not differ significantly between groups (0.51 per 100 patient-years versus 0.71 per 100 patient-years, respectively; hazard ratio, 0.730 [95% CI, 0.206-2.588]). Conclusions: The combination of cilostazol and clopidogrel significantly reduced the recurrence of ischemic stroke without increasing the bleeding risk in noncardioembolic, high-risk patients.
KW - cilostazol
KW - clopidogrel
KW - dual anti-platelet therapy
KW - high-risk
KW - noncardioembolic ischemic stroke
KW - secondary prevention
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U2 - 10.1161/STROKEAHA.121.034378
DO - 10.1161/STROKEAHA.121.034378
M3 - Article
C2 - 34404237
AN - SCOPUS:85118892806
SN - 0039-2499
VL - 52
SP - 3430
EP - 3439
JO - Stroke
JF - Stroke
IS - 11
ER -