西洛他唑双重抗血小板治疗用于腔隙性脑卒中介入预防：CSPS.com试验的亚组分析

Dual Antiplatelet Therapy With Cilostazol for Secondary Prevention in Lacunar Stroke: Subanalysis of the CSPS.com Trial.

作者信息

Nishiyama Yasuhiro, Kimura Kazumi, Otsuka Toshiaki, Toyoda Kazunori, Uchiyama Shinichiro, Hoshino Haruhiko, Sakai Nobuyuki, Okada Yasushi, Origasa Hideki, Naritomi Hiroaki, Houkin Kiyohiro, Yamaguchi Keiji, Minematsu Kazuo, Matsumoto Masayasu, Tominaga Teiji, Tomimoto Hidekazu, Terayama Yasuo, Yasuda Satoshi, Yamaguchi Takenori

机构信息

Department of Neurology (Y.N., K.K.), Graduate School of Medicine, Nippon Medical School, Tokyo, Japan.

Department of Hygiene and Public Health (T.O.), Graduate School of Medicine, Nippon Medical School, Tokyo, Japan.

出版信息

Stroke. 2023 Mar;54(3):697-705. doi: 10.1161/STROKEAHA.122.039900. Epub 2023 Feb 3.

DOI:10.1161/STROKEAHA.122.039900

PMID:36734235

Abstract

BACKGROUND

The effectiveness of long-term dual antiplatelet therapy (DAPT) to prevent recurrent strokes in patients with lacunar stroke remains unclarified. Therefore, this study aimed to compare and to elucidate the safety and effectiveness of DAPT and single antiplatelet therapy (SAPT) in preventing recurrence in chronic lacunar stroke.

METHODS

CSPS.com (Cilostazol Stroke Prevention Study for Antiplatelet Combination) was a prospective, multicenter, randomized controlled trial. In this prespecified subanalysis, 925 patients (mean age, 69.5 years; 69.4% men) with lacunar stroke were selected from 1884 patients with high-risk noncardioembolic stroke, enrolled in the CSPS.com trial after 8 to 180 days following stroke. Patients were randomly assigned to receive either SAPT or DAPT using cilostazol and were followed for 0.5 to 3.5 years. The primary efficacy outcome was the first recurrence of ischemic stroke. The safety outcomes were severe or life-threatening bleeding.

RESULTS

The DAPT group receiving cilostazol and either aspirin or clopidogrel and SAPT group receiving aspirin or clopidogrel alone comprised 464 (50.2%) and 461 (49.8%) patients, respectively. Ischemic stroke occurred in 12 of 464 patients (1.84 per 100 patient-years) in the DAPT group and 31 of 461 patients (4.42 per 100 patient-years) in the SAPT group, during follow-up. After adjusting for multiple potential confounding factors, ischemic stroke risk was significantly lower in the DAPT group than in the SAPT group (hazard ratio, 0.43 [95% CI, 0.22-0.84]). The rate of severe or life-threatening hemorrhage did not differ significantly between the groups (2 patients [0.31 per 100 patient-years] versus 6 patients [0.86 per 100 patient-years] in the DAPT and SAPT groups, respectively; hazard ratio, 0.36 [95% CI, 0.07-1.81]).

CONCLUSIONS

In patients with lacunar stroke, DAPT using cilostazol had significant benefits in reducing recurrent ischemic stroke incidence compared with SAPT without increasing the risk of severe or life-threatening bleeding.

REGISTRATION

URL: https://www.

CLINICALTRIALS

gov; Unique identifier: NCT01995370. URL: https://www.umin.ac.jp/ctr; Unique identifier: UMIN000012180.

摘要

背景

长期双重抗血小板治疗（DAPT）预防腔隙性卒中患者复发性卒中的有效性尚不清楚。因此，本研究旨在比较并阐明DAPT和单一抗血小板治疗（SAPT）在预防慢性腔隙性卒中复发方面的安全性和有效性。

方法

CSPS.com（西洛他唑抗血小板联合卒中预防研究）是一项前瞻性、多中心、随机对照试验。在这项预先设定的亚组分析中，从1884例高危非心源性卒中患者中选取925例（平均年龄69.5岁；男性占69.4%）腔隙性卒中患者，这些患者在卒中后8至180天入选CSPS.com试验。患者被随机分配接受使用西洛他唑的SAPT或DAPT，并随访0.5至3.5年。主要疗效结局是缺血性卒中的首次复发。安全性结局是严重或危及生命的出血。

结果

接受西洛他唑联合阿司匹林或氯吡格雷的DAPT组和单独接受阿司匹林或氯吡格雷的SAPT组分别有464例（50.2%）和461例（49.8%）患者。随访期间，DAPT组464例患者中有12例发生缺血性卒中（每100患者年1.84例），SAPT组461例患者中有31例发生缺血性卒中（每100患者年4.42例）。在调整多个潜在混杂因素后，DAPT组的缺血性卒中风险显著低于SAPT组（风险比，0.43[95%CI，0.22 - 0.84]）。两组间严重或危及生命的出血发生率无显著差异（DAPT组和SAPT组分别为2例[每100患者年0.31例]和6例[每100患者年0.86例]；风险比，0.36[95%CI，0.07 - 1.81]）。