Fan Xueming, Shen Wei, Wang Liuding, Zhang Yunling
Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China.
Front Pharmacol. 2022 Jan 25;12:810297. doi: 10.3389/fphar.2021.810297. eCollection 2021.
Poststroke cognitive impairment (PSCI) is a common complication observed after stroke. Current pharmacologic therapies have no definitive evidence for cognitive recovery or disease progression. Recent studies have verified the positive effect of DL-3-n-butylphthalide (NBP). However, the clinical efficacy and safety are still unclear. The aim of this study was to assess the efficacy of NBP and its harmful effect in the treatment of PSCI. Eligible randomized controlled trials (RCTs) were retrieved from inception to June 2021 from seven medical databases and two clinical registries. The revised Cochrane risk of bias tool (RoB 2.0) was used for methodological quality. RevMan v5.4.1 from Cochrane Collaboration was used for statistical analysis, and Hartung-Knapp-Sidik-Jonkman (HKSJ) method was used for post hoc testing depend on the number of studies. This study has been submitted to PROSPERO with registration number is CRD42021274123. We identified 26 studies with a total sample size of 2,571 patients. The results of this study showed that NBP as monotherapy or combination therapy had better performance in increasing the MoCA (monotherapy: SMD = 1.05, 95% CI [0.69, 1.42], < 0.00001; SMD = 1.06, 95% CI [0.59, 1.52], < 0.00001. combination: SMD = 0.81, 95% CI [0.62, 1.01], < 0.00001; SMD = 0.90, 95% CI [0.46, 1.33], < 0.0001; SMD = 1.04, 95% CI [0.71, 1.38], < 0.00001), MMSE (monotherapy: MD = 4.89, 95% CI [4.14, 5.63]), < 0.00001). combination: SMD = 1.26, 95% CI [0.97, 1.56], < 0.00001; SMD = 1.63, 95% CI [1.28, 1.98], < 0.00001; SMD = 2.13, 95% CI [1.52, 2.75], < 0.00001) and BI (monotherapy: MD = 13.53, HKSJ 95% CI [9.84, 17.22], = 0.014. combination: SMD = 2.24, HKSJ 95%CI [0.37, 4.11], = 0.032; SMD = 3.36, 95%CI [2.80, 3.93], < 0.00001; SMD = 1.48, 95%CI [1.13, 1.83], < 0.00001); and decreasing the NIHSS (monotherapy: MD = -3.86, 95% CI [-5.22, -2.50], < 0.00001. combination: SMD = -1.15, 95% CI [-1.31, -0.98], < 0.00001; SMD = -1.82, 95% CI [-2.25, -1.40], < 0.00001) and CSS (combination: MD = -7.11, 95% CI [-8.42, -5.80], < 0.00001), with no serious adverse reactions observed. The funnel plot verified the possibility of publication bias. NBP maintains a stable pattern in promoting the recovery of cognitive function and abilities of daily living, as well as reducing the symptoms of neurological deficits. However, there is still a need for more high-quality RCTs to verify its efficacy and safety.
卒中后认知障碍（PSCI）是卒中后常见的并发症。目前的药物治疗对于认知功能恢复或疾病进展尚无确凿证据。近期研究证实了丁苯酞（NBP）的积极作用。然而，其临床疗效和安全性仍不明确。本研究旨在评估NBP治疗PSCI的疗效及其不良影响。从7个医学数据库和2个临床注册库中检索自数据库建立至2021年6月符合条件的随机对照试验（RCT）。采用修订的Cochrane偏倚风险工具（RoB 2.0）评估方法学质量。使用Cochrane协作网的RevMan v5.4.1进行统计分析，并根据研究数量采用Hartung-Knapp-Sidik-Jonkman（HKSJ）方法进行事后检验。本研究已在国际前瞻性系统评价注册库（PROSPERO）注册，注册号为CRD42021274123。我们纳入了26项研究，总样本量为2571例患者。研究结果表明，NBP单药治疗或联合治疗在提高蒙特利尔认知评估量表（MoCA）得分（单药治疗：标准化均数差（SMD）=1.05，95%置信区间（CI）[0.69，1.42]，P<0.00001；SMD = 1.06，95%CI [0.59，1.52]，P<0.00001。联合治疗：SMD = 0.81，95%CI [0.62，1.01]，P<0.00001；SMD = 0.90，95%CI [0.46，1.33]，P<0.0001；SMD = 1.04，95%CI [0.71，1.38]，P<0.000s）、简易精神状态检查表（MMSE）得分（单药治疗：均数差（MD）=4.89，95%CI [4.14，5.63]，P<0.00001）。联合治疗：SMD = 1.26，95%CI [0.97，1.56]，P<0.00001；SMD = 1.63，95%CI [1.28，1.98]，P<0.00001；SMD = 2.13，95%CI [1.52，2.75]，P<0.00001）和Barthel指数（BI）得分（单药治疗：MD = 13.53，HKSJ 95%CI [9.84，17.22]，P = 0.014。联合治疗：SMD = 2.24，HKSJ 95%CI [0.37，4.11]，P = 0.032；SMD = 3.36，95%CI [2.80，3.93]，P<0.00001；SMD = 1.48，95%CI [1.13，1.83]，P<0.00001）方面表现更好；在降低美国国立卫生研究院卒中量表（NIHSS）得分（单药治疗：MD = -3.86，95%CI [-5.22，-2.50]，P<0.00001。联合治疗：SMD = -1.15，95%CI [-1.31，-0.98]，P<0.00001；SMD = -1.82，95%CI [-2.25，-1.40]，P<0.00001）和中国卒中量表（CSS）得分（联合治疗：MD = -7.11，95%CI [-8.42，-5.80]，P<0.00001）方面也表现更好，且未观察到严重不良反应。漏斗图分析证实了存在发表偏倚的可能性。NBP在促进认知功能和日常生活能力恢复以及减轻神经功能缺损症状方面保持稳定疗效。然而，仍需要更多高质量的RCT来验证其疗效和安全性。
