Dávalos Antoni, Castillo José, Alvarez-Sabín José, Secades Julio J, Mercadal Joan, López Sonia, Cobo Erik, Warach Steven, Sherman David, Clark Wayne M, Lozano Rafael
Department of Neurology, Hospital Universitari Doctor Josep Trueta, Girona, Spain.
Stroke. 2002 Dec;33(12):2850-7. doi: 10.1161/01.str.0000038691.03334.71.
No single neuroprotective agent has been shown to influence outcome after acute stroke. Citicoline has been studied worldwide in many clinical trials with positive findings, but only 1 trial has obtained significant results in the primary efficacy variables. Our objective was to evaluate the effects of oral citicoline in patients with acute ischemic stroke by a data pooling analysis of clinical trials. The primary efficacy end point chosen was the common evaluation of recovery, combining National Institutes of Health Stroke Scale </=1, modified Rankin Scale score </=1, and Barthel Index >/=95 at 3 months using the generalized estimating equations analysis.
A systematic search of all prospective, randomized, placebo-controlled, double-blind clinical trials with oral citicoline (MEDLINE, Cochrane, and Ferrer Group bibliographic databases) was undertaken. Individual patient data were extracted from each study and pooled in a single data file. The main inclusion criteria included compatible neuroimaging with ischemic stroke, National Institutes of Health Stroke Scale >/=8, and prior modified Rankin Scale score </=1. Four clinical trials using various doses of oral citicoline (500, 1000, and 2000 mg) were identified.
Of 1652 randomized patients, 1372 fulfilled the inclusion criteria (583 received placebo, 789 received citicoline). Recovery at 3 months was 25.2% in citicoline-treated patients and 20.2% in placebo-treated patients (odds ratio [OR], 1.33; 95% CI, 1.10 to 1.62; P=0.0034). The dose showing the largest difference with placebo was 2000 mg, with 27.9% of patients achieving recovery (OR, 1.38; 95% CI, 1.10 to 1.72; P=0.0043). The overall safety of citicoline was similar to placebo.
Treatment with oral citicoline within the first 24 hours after onset in patients with moderate to severe stroke increases the probability of complete recovery at 3 months.
尚无单一神经保护剂被证实可影响急性卒中后的预后。胞磷胆碱已在全球范围内进行了多项临床试验，结果呈阳性，但仅有1项试验在主要疗效变量方面取得显著结果。我们的目的是通过对临床试验进行数据汇总分析，评估口服胞磷胆碱对急性缺血性卒中患者的影响。选择的主要疗效终点是综合恢复情况评估，即使用广义估计方程分析，在3个月时美国国立卫生研究院卒中量表（NIHSS）评分≤1、改良Rankin量表评分≤1且Barthel指数≥95。
对所有使用口服胞磷胆碱的前瞻性、随机、安慰剂对照、双盲临床试验进行系统检索（MEDLINE、Cochrane和Ferrer集团书目数据库）。从每项研究中提取个体患者数据，并汇总到单个数据文件中。主要纳入标准包括与缺血性卒中相符的神经影像学检查、NIHSS评分≥8以及既往改良Rankin量表评分≤1。共识别出4项使用不同剂量口服胞磷胆碱（500、1000和2000mg）的临床试验。
1652例随机分组患者中，1372例符合纳入标准（583例接受安慰剂，789例接受胞磷胆碱）。胞磷胆碱治疗组患者3个月时的恢复率为25.2%，安慰剂治疗组为20.2%（优势比[OR]，1.33；95%置信区间[CI]，1.10至1.62；P = 0.0034）。与安慰剂差异最大的剂量为2000mg，27.9%的患者实现恢复（OR，1.38；95%CI，1.10至1.72；P = 0.0 ————————文档中此处有误，应为P = 0.0043）。胞磷胆碱的总体安全性与安慰剂相似。
对于中重度卒中患者，在发病后24小时内口服胞磷胆碱治疗可增加3个月时完全恢复的可能性。
