法舒地尔治疗缺血性脑卒中疗效及安全性的系统评价
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摘要
目的系统评价法舒地尔(fasudil，FSD)治疗缺血性脑卒中(ischemic stroke)的疗效和安全性。
方法计算机检索Cochrane协作网临床对照试验中心注册数据库（CENTRAL，2011年第4期）、Medline(1950-2011年11月)、Embase（1980－2011年11月）、CBM（1978-2011年11月）、CNKI（1979－2011年11月）、VIP（1989-2011年11月）、万方数据库（1982-2011年11月）等，手工检索中华神经科杂志、中风与神经病疾杂志、临床神经病学杂志等十余种相关杂志，追查已纳入文献的参考文献、相关的会议文献，收集国内外关于法舒地尔治疗缺血性脑卒中的随机对照试验（RCT）。按照Cochrane协作网系统评价的方法，由两名评价员独立进行质量评价和资料提取，采用RevMan 5.0.25软件进行统计学分析。
结果共纳入83篇已发表文献（8102例患者），包括3个安慰剂对照试验、38个阴性对照试验和42个阳性对照试验。结果显示:①病死率:与对照组比较，法舒地尔组随访3个月病死率的差异无统计学意义。②残疾率：6个研究采用MRS评分评价残疾改善有效率，17个研究采用BI评分评价患者日常生活能力状态，分别进行Meta分析,提示法舒地尔可以明显改善患者MRS及BI评分情况，与对照组比较差异有统计学意义。③神经功能缺损改善情况：57个研究采用CSS评分、10个研究采用NIHSS评分、10个研究采用ESS评分、5个研究采用SSS评分、1个研究采用JSS评分,我们根据使用的量表不同分别进行Meta分析,除了4个CSS评分的阴性对照研究、3个NIHSS评分阳性对照研究、4个ESS评分阳性对照研究提示法舒地尔组神经功能缺损改善优于对照组而两组神经功能缺损改善情况未达到统计学意义外,其余提示法舒地尔组神经功能缺损改善优于对照组且差异有统计学意义。④不良反应：法舒地尔不良反应主要有头痛、头晕、颜面潮红、低血压等，57个研究报道了不良反应,法舒地尔组不良反应发生率比对照组高,但程度轻微，不影响治疗。⑤生存质量评价：未进行生存质量评价。
结论本系统评价结果提示法舒地尔能有效改善缺血性脑卒中患者神经功能缺损情况，减轻残疾功能状态，提高患者的日常生活能力而且不良反应少，未发现严重不良反应，临床应用安全。此次纳入的研究大部分质量不高,可能存在选择性偏倚、测量性偏倚和实施偏倚,影响了结论的可靠性,研究的方法学质量有待进一步提高。我们期待开展大样本、多中心、高质量的随机对照试验（RCT）,能够报道长期随访指标,充分和规范报告不良反应,以获得更为科学可靠的证据。
Objective To assess the effectiveness and safety of fasudil for patients with ischemicstroke.
Methods We searched The Cochrane Central Register of Controlled Trials(Issue 4,2011),Medline(1950 to November 2011),Embase（1980 to November 2011）,CBM（1978 to November2011）,CNKI（1979 to November 2011）,VIP（1989 to November 2011）,Wanfang Database（1982 to November 2011）by electronic database and relevant journals such as Chinese Journalof Neurology, Journal of Apoplexy and Nervous, Journal of Clinical Neurology etc.by manualsearching to collect all randomized controlled trials(RCT) of fasudil for patients with ischemicstroke.Two reviewers independently selected studies,assessed quality of studies and extracteddata according to the methods recommended by the Cochrane Handbook for Systematic Reviewsof Interventions.The RevMan 5.0 software was used for statistical analysis.
Results Eighty-three studies involving 8102 patients were included,of which 3 wereplacebo-controlled,38 were negative controlled and 42 were positive controlled. The resultsshowed that:①Mortality: compared with the control group, mortality difference in fasudilgroups followed for 3 month had no statistical significance.②Disability: Meta analysis of 6studies using MRS score in the evaluation of disabilities improve efficiency, 17 studies using BIscore in the evaluation of activities of daily living , respectively suggested that fasudil cansignificantly improve patients with MRS and BI score, compared with the control group, and thedifference was statistically significant.③Neurologic deficits changes: Meta analysis of 57 studiesusing CSS score, 10 studies using NIHSS score, 10 studies using ESS score, 5 studies using SSSscore,1 study using by JSS score, according to the use of the scale respectively,suggested thatNeurological deficits improved of fasudil was better than the control group and the differencewas statistically significant, in addition to the 4 CSS score of negative case-control study, 3NIHSS score of positive control studies, 4 ESS score of positive control study did not reachstatistical significance.④Adverse events: Adverse events were reported in 57 studies. headache,dizziness, facial flushing, hypotension were the major adverse events of fasudil. Adverse eventsrates of fasudil were higher than the control group, but the extent of minor, adverse events didnot influence the treatment.⑤Quality of live was not assessed in any of the studies.
Conclusion Fasudil can effectively improve the neurological function after ischemic stroke, reduce functional disability status, improve the patients' activities of daily living and appears tobe safe. This included most of the quality is low,and there may be selection bias, measurementbias and performance bias, affecting the reliability of the conclusion. the methodological qualityof research needs to be further improved.We look forward to developing a large sample,multi-center, high quality randomized controlled trials (RCT) , long-term follow-up index,fully and standardize the reporting of adverse reactions, in order to obtain more reliablescientific evidence.
方法计算机检索Cochrane协作网临床对照试验中心注册数据库（CENTRAL，2011年第4期）、Medline(1950-2011年11月)、Embase（1980－2011年11月）、CBM（1978-2011年11月）、CNKI（1979－2011年11月）、VIP（1989-2011年11月）、万方数据库（1982-2011年11月）等，手工检索中华神经科杂志、中风与神经病疾杂志、临床神经病学杂志等十余种相关杂志，追查已纳入文献的参考文献、相关的会议文献，收集国内外关于法舒地尔治疗缺血性脑卒中的随机对照试验（RCT）。按照Cochrane协作网系统评价的方法，由两名评价员独立进行质量评价和资料提取，采用RevMan 5.0.25软件进行统计学分析。
结果共纳入83篇已发表文献（8102例患者），包括3个安慰剂对照试验、38个阴性对照试验和42个阳性对照试验。结果显示:①病死率:与对照组比较，法舒地尔组随访3个月病死率的差异无统计学意义。②残疾率：6个研究采用MRS评分评价残疾改善有效率，17个研究采用BI评分评价患者日常生活能力状态，分别进行Meta分析,提示法舒地尔可以明显改善患者MRS及BI评分情况，与对照组比较差异有统计学意义。③神经功能缺损改善情况：57个研究采用CSS评分、10个研究采用NIHSS评分、10个研究采用ESS评分、5个研究采用SSS评分、1个研究采用JSS评分,我们根据使用的量表不同分别进行Meta分析,除了4个CSS评分的阴性对照研究、3个NIHSS评分阳性对照研究、4个ESS评分阳性对照研究提示法舒地尔组神经功能缺损改善优于对照组而两组神经功能缺损改善情况未达到统计学意义外,其余提示法舒地尔组神经功能缺损改善优于对照组且差异有统计学意义。④不良反应：法舒地尔不良反应主要有头痛、头晕、颜面潮红、低血压等，57个研究报道了不良反应,法舒地尔组不良反应发生率比对照组高,但程度轻微，不影响治疗。⑤生存质量评价：未进行生存质量评价。
结论本系统评价结果提示法舒地尔能有效改善缺血性脑卒中患者神经功能缺损情况，减轻残疾功能状态，提高患者的日常生活能力而且不良反应少，未发现严重不良反应，临床应用安全。此次纳入的研究大部分质量不高,可能存在选择性偏倚、测量性偏倚和实施偏倚,影响了结论的可靠性,研究的方法学质量有待进一步提高。我们期待开展大样本、多中心、高质量的随机对照试验（RCT）,能够报道长期随访指标,充分和规范报告不良反应,以获得更为科学可靠的证据。
Objective To assess the effectiveness and safety of fasudil for patients with ischemicstroke.
Methods We searched The Cochrane Central Register of Controlled Trials(Issue 4,2011),Medline(1950 to November 2011),Embase（1980 to November 2011）,CBM（1978 to November2011）,CNKI（1979 to November 2011）,VIP（1989 to November 2011）,Wanfang Database（1982 to November 2011）by electronic database and relevant journals such as Chinese Journalof Neurology, Journal of Apoplexy and Nervous, Journal of Clinical Neurology etc.by manualsearching to collect all randomized controlled trials(RCT) of fasudil for patients with ischemicstroke.Two reviewers independently selected studies,assessed quality of studies and extracteddata according to the methods recommended by the Cochrane Handbook for Systematic Reviewsof Interventions.The RevMan 5.0 software was used for statistical analysis.
Results Eighty-three studies involving 8102 patients were included,of which 3 wereplacebo-controlled,38 were negative controlled and 42 were positive controlled. The resultsshowed that:①Mortality: compared with the control group, mortality difference in fasudilgroups followed for 3 month had no statistical significance.②Disability: Meta analysis of 6studies using MRS score in the evaluation of disabilities improve efficiency, 17 studies using BIscore in the evaluation of activities of daily living , respectively suggested that fasudil cansignificantly improve patients with MRS and BI score, compared with the control group, and thedifference was statistically significant.③Neurologic deficits changes: Meta analysis of 57 studiesusing CSS score, 10 studies using NIHSS score, 10 studies using ESS score, 5 studies using SSSscore,1 study using by JSS score, according to the use of the scale respectively,suggested thatNeurological deficits improved of fasudil was better than the control group and the differencewas statistically significant, in addition to the 4 CSS score of negative case-control study, 3NIHSS score of positive control studies, 4 ESS score of positive control study did not reachstatistical significance.④Adverse events: Adverse events were reported in 57 studies. headache,dizziness, facial flushing, hypotension were the major adverse events of fasudil. Adverse eventsrates of fasudil were higher than the control group, but the extent of minor, adverse events didnot influence the treatment.⑤Quality of live was not assessed in any of the studies.
Conclusion Fasudil can effectively improve the neurological function after ischemic stroke, reduce functional disability status, improve the patients' activities of daily living and appears tobe safe. This included most of the quality is low,and there may be selection bias, measurementbias and performance bias, affecting the reliability of the conclusion. the methodological qualityof research needs to be further improved.We look forward to developing a large sample,multi-center, high quality randomized controlled trials (RCT) , long-term follow-up index,fully and standardize the reporting of adverse reactions, in order to obtain more reliablescientific evidence.
引文
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