Cilostazol for prevention of secondary stroke (CSPS 2): an aspirin-controlled, double-blind, randomised non-inferiority trial
Cilostazol for prevention of secondary stroke (CSPS 2): an aspirin-controlled, double-blind, randomised non-inferiority trial
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DOI：
10.1016/s1474-4422(10)70198-8
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发表时间：
2010-10-01
期刊：
影响因子：
48
通讯作者：
Hamada, Chikuma
中科院分区：
文献类型：
--
作者：
Shinohara, Yukito;Katayama, Yasuo;Hamada, Chikuma
背景与安慰剂相比，抗血小板药物西洛他唑可有效预防卒中复发。我们设计了第二项西洛他唑卒中预防研究（CSPS 2），以确定西洛他唑与阿司匹林相比在预防卒中方面的非劣效性，比较西洛他唑和阿司匹林治疗非心源性脑梗死的疗效和安全性。在日本的278个研究中心招募了79名在过去26周内患有脑梗死的老年人，并将其分配接受100 mg西洛他唑每日2次或81 mg西洛他唑每日2次。每天服用一次阿司匹林，持续1-5年。使用登记时获得的患者信息，通过动态平衡方法，根据计算机生成的随机化序列分配患者。所有患者、研究人员、研究者和申办者均对治疗分配设盲。主要终点是首次发生卒中（脑梗死、脑出血或蛛网膜下腔出血）。预定义的非劣效性界值为风险比1.33的95% CI上限。按全分析集进行分析。该试验注册于ClinicalTrials.gov，编号NCT 00234065。结果在2003年12月至2006年10月期间，2757名患者被招募并随机分配接受西洛他唑（n=1379）或阿司匹林（n=1378），其中1337名患者接受西洛他唑治疗，1335名患者接受阿司匹林治疗;平均随访时间为29个月（SD 16）。西洛他唑组的主要终点发生率为2.76%（n=82），阿司匹林组为3.71%（n=119）（风险比0.743，95%CI 0.564- 0.564）。981; p=0.0357）。西洛他唑组（0.77%，n=23）发生出血事件（脑出血、蛛网膜下腔出血或需要住院的出血）的患者少于阿司匹林组（1.78%，n=57; 0.458，0.296-0 . 711; p=0.0004），但西洛他唑组中头痛、腹泻、心悸、头晕和心动过速的发生率高于阿司匹林组。因此，西洛他唑可用于预防非心源性卒中患者的卒中。
Background The antiplatelet drug cilostazol is efficacious for prevention of stroke recurrence compared with placebo. We designed the second Cilostazol Stroke Prevention Study (CSPS 2) to establish non-inferiority of cilostazol versus aspirin for prevention of stroke, and to compare the efficacy and safety of cilostazol and aspirin in patients with non-cardioembolic ischaemic stroke.Methods Patients aged 20-79 years who had had a cerebral infarction within the previous 26 weeks were enrolled at 278 sites in Japan and allocated to receive 100 mg cilostazol twice daily or 81 mg aspirin once daily for 1-5 years. Patients were allocated according to a computer-generated randomisation sequence by means of a dynamic balancing method using patient information obtained at registration. All patients, study personnel, investigators, and the sponsor were masked to treatment allocation. The primary endpoint was the first occurrence of stroke (cerebral infarction, cerebral haemorrhage, or subarachnoid haemorrhage). The predefined margin of non-inferiority was an upper 95% CI limit for the hazard ratio of 1.33. Analyses were by full-analysis set. This trial is registered with ClinicalTrials.gov, number NCT00234065.Findings Between December, 2003, and October, 2006,2757 patients were enrolled and randomly allocated to receive cilostazol (n=1379) or aspirin (n=1378), of whom 1337 on cilostazol and 1335 on aspirin were included in analyses; mean follow-up was 29 months (SD 16). The primary endpoint occurred at yearly rates of 2.76% (n=82) in the cilostazol group and 3.71% (n=119) in the aspirin group (hazard ratio 0.743, 95% CI 0.564-0 . 981; p=0.0357). Haemorrhagic events (cerebral haemorrhage, subarachnoid haemorrhage, or haemorrhage requiring hospital admission) occurred in fewer patients on cilostazol (0.77%, n=23) than on aspirin (1.78%, n=57; 0.458, 0.296-0 . 711; p=0.0004), but headache, diarrhoea, palpitation, dizziness, and tachycardia were more frequent in the cilostazol group than in the aspirin group.Interpretation Cilostazol seems to be non-inferior, and might be superior, to aspirin for prevention of stroke after an ischaemic stroke, and was associated with fewer haemorrhagic events. Therefore, cilostazol could be used for prevention of stroke in patients with non-cardioembolic stroke.Funding Otsuka Pharmaceutical.