西洛他唑联合阿司匹林或氯吡格雷双联抗血小板治疗：CSPS.com 试验的亚组分析。
Dual Antiplatelet Therapy Using Cilostazol With Aspirin or Clopidogrel: Subanalysis of the CSPS.com Trial.
机构信息
Department of Neurology, Tokyo Saiseikai Central Hospital, Japan (H.H.).
Department of Cerebrovascular Medicine (K. Toyoda, T.Y.), National Cerebral and Cardiovascular Center, Suita, Japan.
出版信息
Stroke. 2021 Nov;52(11):3430-3439. doi: 10.1161/STROKEAHA.121.034378. Epub 2021 Aug 18.
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.
REGISTRATION
URL: https://www.clinicaltrials.gov; Unique identifier: NCT01995370. URL: https://www.umin.ac.jp/ctr/; Unique identifier: UMIN000012180.
背景与目的
与单药治疗相比，双联抗血小板治疗（DAPT）联合阿司匹林和氯吡格雷可降低缺血性卒中的复发风险，但显著增加出血事件。CSPS.com 试验（西洛他唑预防卒中研究联合）表明，使用西洛他唑的 DAPT 更有效，且无出血风险。在 CSPS.com 试验中，阿司匹林或氯吡格雷被用作基础抗血小板药物。本研究旨在评估和明确每种联合用药的有效性和安全性。
方法
在 CSPS.com 试验中，这是一项多中心、开放标签、随机对照研究，纳入了发病 8180 天后接受阿司匹林或氯吡格雷单药治疗的高风险非心源性缺血性卒中患者，由主管医生决定。患者被随机分配接受西洛他唑单药治疗或 DAPT 治疗，并随访 0.53.5 年。主要疗效结局为首次缺血性卒中复发。安全性结局为严重或危及生命的出血。分析基于基础抗血小板药物。
结果
共纳入 763 例服用阿司匹林的患者和 1116 例服用氯吡格雷的患者进行意向治疗分析。尽管氯吡格雷组的危险因素多于阿司匹林组，但两组间主要疗效结局和安全性结局无显著差异。在阿司匹林组中，DAPT 组与阿司匹林单药组之间主要疗效结局和安全性结局无显著差异。在氯吡格雷组中，DAPT 组的主要终点发生率为 2.31/100 患者年，氯吡格雷单药组为 5.19/100 患者年（风险比，0.447[95%CI，0.2580.774]）。两组间安全性结局无显著差异（分别为 0.51/100 患者年和 0.71/100 患者年，风险比，0.730[95%CI，0.2062.588]）。
结论
西洛他唑联合氯吡格雷可显著降低非心源性、高危患者缺血性卒中的复发风险，且不增加出血风险。
注册信息
网址：https://www.clinicaltrials.gov；唯一标识符：NCT01995370。网址：https://www.umin.ac.jp/ctr/；唯一标识符：UMIN000012180。
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