用于杜氏肌营养不良症的钙拮抗剂。

Calcium antagonists for Duchenne muscular dystrophy.

作者信息

Phillips Margaret F, Quinlivan Rosaline

机构信息

Division of Rehabilitation Medicine, University of Nottingham, Arkwright House, Derby City Hospital, Derby, UK, DE22 3NE.

出版信息

Cochrane Database Syst Rev. 2008 Oct 8;2008(4):CD004571. doi: 10.1002/14651858.CD004571.pub2.

Abstract

BACKGROUND

Duchenne muscular dystrophy (DMD) is a progressive muscle condition starting in childhood, leading to severe disability and a shortened life span. It is due to severe deficiency of the protein dystrophin which performs both structural and signalling roles within skeletal and cardiac myocytes. Calcium accumulates in dystrophic muscle cells and plays a role in cell damage. It has been hypothesised that use of calcium antagonists might reduce this calcium load and its toxic effect on muscle cells.

OBJECTIVES

To evaluate the effects of calcium antagonists on muscle function and muscle strength in people with DMD.

SEARCH STRATEGY

The Cochrane Neuromuscular Disease Group Trials Register (February 2008), MEDLINE (from January 1950 to March 2008) and EMBASE (from January 1947 to March 2008) were searched. Search terms were 'calcium antagonists' or 'calcium channel blocker' or 'dantrolene' or 'verapamil' or 'nifedipine' or 'flunarizine' or 'diltiazem' or 'amlodipine' or 'nicardipine' and 'Muscular Dystrophy, Duchenne'. Bibliographies in reports of any trials were also searched.

SELECTION CRITERIA

All randomised or quasi-randomised controlled trials of any calcium antagonist in people with DMD.

DATA COLLECTION AND ANALYSIS

Both authors assessed all identified trials for inclusion in the study on the basis of whether they fulfilled the selection criteria. Both authors extracted data from the trials and assessed the methodological quality. Had there been more than one trial of the same intervention and outcome of sufficient methodological quality, we had planned to undertake a meta-analysis.

MAIN RESULTS

Five randomised or quasi-randomised double-blind trials fulfilled the selection criteria, but were not sufficiently comparable to undertake a meta-analysis. The drugs studied were verapamil (8 participants), diltiazem (56 participants), nifedipine (105 participants) and flunarizine (27 participants). There were limitations in the description of blinding and randomisation, and definition of outcome measures. One trial, using verapamil, showed a difference between groups in muscle force measured by ergometry, but also revealed cardiac side effects. The numbers of people included in the trials were low, and so the studies may not have included enough people for sufficient power to detect small differences in muscle force or function between placebo and control groups. In addition, calcium antagonists were in an early stage of development and some of the second generation drugs that have a better side effect profile, such as amlodipine, have not been studied.

AUTHORS' CONCLUSIONS: There is no evidence to show a significant beneficial effect of calcium antagonists on muscle function in DMD.

摘要

背景

杜氏肌营养不良症(DMD)是一种始于儿童期的进行性肌肉疾病,会导致严重残疾并缩短寿命。它是由于蛋白质肌营养不良蛋白严重缺乏所致,该蛋白在骨骼肌和心肌细胞中兼具结构和信号传导作用。钙在营养不良的肌肉细胞中蓄积,并在细胞损伤中发挥作用。据推测,使用钙拮抗剂可能会减少这种钙负荷及其对肌肉细胞的毒性作用。

目的

评估钙拮抗剂对DMD患者肌肉功能和肌肉力量的影响。

检索策略

检索了Cochrane神经肌肉疾病组试验注册库(2008年2月)、MEDLINE(1950年1月至2008年3月)和EMBASE(1947年1月至2008年3月)。检索词为“钙拮抗剂”或“钙通道阻滞剂”或“丹曲林”或“维拉帕米”或“硝苯地平”或“氟桂利嗪”或“地尔硫䓬”或“氨氯地平”或“尼卡地平”以及“杜氏肌营养不良症”。还检索了任何试验报告中的参考文献。

选择标准

所有关于DMD患者使用任何钙拮抗剂的随机或半随机对照试验。

数据收集与分析

两位作者根据试验是否符合选择标准,评估了所有确定的试验是否纳入本研究。两位作者从试验中提取数据并评估方法学质量。如果针对同一干预措施和结局有多项方法学质量足够的试验,我们计划进行荟萃分析。

主要结果

五项随机或半随机双盲试验符合选择标准,但可比性不足,无法进行荟萃分析。所研究的药物有维拉帕米(8名参与者)、地尔硫䓬(56名参与者)、硝苯地平(105名参与者)和氟桂利嗪(27名参与者)。在盲法和随机化描述以及结局指标定义方面存在局限性。一项使用维拉帕米的试验显示,通过测力计测量的肌肉力量在组间存在差异,但也显示出心脏副作用。试验纳入的人数较少,因此这些研究可能没有纳入足够多的人,以至于没有足够的效力来检测安慰剂组和对照组之间肌肉力量或功能的微小差异。此外,钙拮抗剂尚处于研发早期,一些副作用较小的第二代药物,如氨氯地平,尚未得到研究。

作者结论

没有证据表明钙拮抗剂对DMD患者的肌肉功能有显著有益作用。

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