TransLab Research Group, and Department of Medical Sciences, University of Girona, Spain; Research Group on Statistics, Econometrics and Health, University of Girona, Spain; CIBER of Epidemiology and Public Health, Spain; Girona Biomedical Research Institute, Salt, Spain.
Int J Neuropsychopharmacol. 2017 Jul 1;20(7):519-528. doi: 10.1093/ijnp/pyx012.
We investigated the effect of cholinesterase inhibitors on all-cause discontinuation, efficacy and safety, and the effects of study design-, intervention-, and patient-related covariates on the risk-benefit of cholinesterase inhibitors for Alzheimer's disease.
A systematic review and meta-analysis of randomized placebo-controlled clinical trials comparing cholinesterase inhibitors and placebo was performed. The effect of covariates on study outcomes was analysed by means of meta-regression using a Bayesian framework.
Forty-three randomized placebo-controlled clinical trials involving 16106 patients were included. All-cause discontinuation was higher with cholinesterase inhibitors (OR = 1.66), as was discontinuation due to adverse events (OR=1.75). Cholinesterase inhibitors improved cognitive function (standardized mean difference = 0.38), global symptomatology (standardized mean difference=0.28) and functional capacity (standardized mean difference=0.16) but not neuropsychiatric symptoms. Rivastigmine was associated with a poorer outcome on all-cause discontinuation (Diff OR = 1.66) and donepezil with a higher efficacy on global change (Diff standardized mean difference = 0.41). The proportion of patients with serious adverse events decreased with age (Diff OR = -0.09). Mortality was lower with cholinesterase inhibitors than with placebo (OR = 0.65).
While cholinesterase inhibitors show a poor risk-benefit relationship as indicated by mild symptom improvement and a higher than placebo all-cause discontinuation, a reduction of mortality was suggested. Intervention- and patient-related factors modify the effect of cholinesterase inhibitors in patients with Alzheimer's disease.
我们研究了胆碱酯酶抑制剂对所有原因停药、疗效和安全性的影响，以及研究设计、干预和患者相关协变量对胆碱酯酶抑制剂治疗阿尔茨海默病的风险效益的影响。
对比较胆碱酯酶抑制剂和安慰剂的随机安慰剂对照临床试验进行了系统评价和荟萃分析。使用贝叶斯框架的荟萃回归分析协变量对研究结果的影响。
纳入了 43 项涉及 16106 名患者的随机安慰剂对照临床试验。与安慰剂相比，胆碱酯酶抑制剂组的全因停药率更高（OR=1.66），因不良事件停药率也更高（OR=1.75）。胆碱酯酶抑制剂改善了认知功能（标准化均数差=0.38）、整体症状（标准化均数差=0.28）和功能能力（标准化均数差=0.16），但对神经精神症状没有影响。加兰他敏与全因停药（差异 OR=1.66）相关，多奈哌齐与整体变化（差异标准化均数差=0.41）相关。严重不良事件的发生率随年龄的增加而降低（差异 OR=-0.09）。与安慰剂相比，胆碱酯酶抑制剂的死亡率更低（OR=0.65）。
虽然胆碱酯酶抑制剂的风险效益关系较差，表现为轻度症状改善和高于安慰剂的全因停药率，但提示死亡率降低。干预和患者相关因素改变了胆碱酯酶抑制剂在阿尔茨海默病患者中的作用。
