日本阿格雷诺克斯（缓释双嘧达莫加阿司匹林）预防卒中与阿司匹林方案（JASAP）研究：一项随机、双盲、对照试验。

The Japanese aggrenox (extended-release dipyridamole plus aspirin) stroke prevention versus aspirin programme (JASAP) study: a randomized, double-blind, controlled trial.

机构信息

Department of Neurology, Tokyo Women's Medical University, Japan.

出版信息

Cerebrovasc Dis. 2011;31(6):601-13. doi: 10.1159/000327035. Epub 2011 Apr 19.

DOI:10.1159/000327035

PMID:21502757

Abstract

BACKGROUND

Despite improvements in treatment, stroke still carries a high death toll and disability in Asia. Extended-release dipyridamole (ER-DP) plus acetylsalicylic acid (ASA) has consistently been shown to be superior over conventional platelet inhibition by ASA. ER-DP plus ASA is well established in the secondary prevention of stroke in a lot of countries including the USA and Europe. DP has an established benefit in the treatment of heart disease in Japan; however, for the prevention of stroke, the fixed-dose combination of ER-DP plus ASA has only been investigated in a small number of patients in Japan.

METHODS

The aim of this double-blind, randomized clinical trial was to investigate the efficacy and safety of ER-DP plus ASA versus 81 mg ASA over 1 year. The primary end point of this study was the event rate of recurrent ischemic stroke (fatal or nonfatal) using the Kaplan-Meier method and Cox regression analysis.

RESULTS

Of the 1,294 enrolled patients, the primary end point was analyzed in 652 patients in the ER-DP plus ASA group and 639 in the ASA group. The incidence of ischemic stroke was 6.9% for ER-DP plus ASA and 5.0% for ASA with a hazard ratio of 1.47 (95% confidence interval 0.93-2.31) for the primary end point. The ASA treatment group was found to have a lower than expected yearly event rate, compared to other studies in Japanese stroke patients. Noninferiority of ER-DP plus ASA versus ASA could not be shown. The risks of major bleeding events and intracranial hemorrhage were found to be similar between the treatment arms. There were 4 deaths (0.6%) in the ER-DP plus ASA group and 10 (1.6%) in the ASA group.

CONCLUSIONS

The results of the study are inconclusive. Noninferiority of ER-DP plus ASA versus ASA could not be established, a difference between treatments could not be shown for the primary end point. Possible reasons for this result include a small sample size, low event rates and too short a treatment duration (ClinicalTrials. gov number, NCT00311402).

摘要

背景

尽管治疗方法有所改善，但亚洲地区的中风死亡率和致残率仍然很高。与传统的阿司匹林血小板抑制相比，缓释双嘧达莫（ER-DP）加乙酰水杨酸（ASA）一直显示出优越性。ER-DP 加 ASA 已在许多国家（包括美国和欧洲）得到广泛应用，用于中风的二级预防。DP 在日本的心脏病治疗中已有明确的获益；然而，对于预防中风，ER-DP 加 ASA 的固定剂量组合仅在少数日本患者中进行了研究。

方法

本双盲、随机临床试验的目的是研究 ER-DP 加 ASA 与 81mg ASA 治疗 1 年的疗效和安全性。本研究的主要终点是使用 Kaplan-Meier 方法和 Cox 回归分析评估复发性缺血性中风（致死性或非致死性）的发生率。

结果

在纳入的 1294 名患者中，主要终点在 ER-DP 加 ASA 组的 652 名患者和 ASA 组的 639 名患者中进行了分析。ER-DP 加 ASA 的中风发生率为 6.9%，ASA 为 5.0%，主要终点的风险比为 1.47（95%置信区间 0.93-2.31）。与日本中风患者的其他研究相比，ASA 治疗组的年事件发生率低于预期。不能证明 ER-DP 加 ASA 不劣于 ASA。治疗组之间主要出血事件和颅内出血的风险相似。ER-DP 加 ASA 组有 4 例死亡（0.6%），ASA 组有 10 例（1.6%）。