Diniz Breno Satler, Pinto Jony Arrais, Gonzaga Maria Luiza Cavichioli, Guimarães Fabiana Meira, Gattaz Wagner Farid, Forlenza Orestes Vicente
Laboratory of Neuroscience (LIM 27), Institute and Department of Psychiatry, Faculty of Medicine, University of Sao Paulo, Rua Ovidio Pires de Campos, 785, 3th floor, Sao Paulo, SP, CEP: 05403-010, Brazil.
Eur Arch Psychiatry Clin Neurosci. 2009 Jun;259(4):248-56. doi: 10.1007/s00406-008-0864-1. Epub 2009 Feb 17.
Individual randomized clinical trials (RCTs) with cholinesterase inhibitors (ChEIs) aiming to delay the progression from mild cognitive impairment (MCI) to Alzheimer's disease (AD) have not found significant benefit of their use for this purpose. The objective of this study is to meta-analyze the RCTs conducted with ChEIs in order to assess whether pooled analysis could show the benefit of these drugs in delaying the progression from MCI to AD.
We searched for references of published and unpublished studies on electronic databases (Medline, Embase, Web of Science, and Clinical Trial Database Registry, particularly the Clinicaltrials.gov--http://www.clinicaltrials.gov ). We retrieved 173 references, which yielded three references for data extraction. A total of 3.574 subjects from four RCTs were included in the meta-analysis. Among 1,784 subjects allocated in the ChEI-treatment group, 275 (15.4%) progressed to AD/dementia, as opposed to 366 (20.4%) out of 1,790 subjects in the placebo group. The relative risk (RR) for progression to AD/dementia in the ChEI-treated group was 0.75 [CI(95%) 0.66-0.87], z = -3.89, P < 0.001. The patients on the ChEI group had a significantly higher all-cause dropout risk than the patients on the placebo group (RR = 1.36 CI(95%) [1.24-1.49]; z = 6.59, P < 0.001). The RR for serious adverse events (SAE) in the ChEI-treated group showed no significantly statistical difference from the placebo group (RR = 0.95 [CI(95%) 0.83-1.09], z = -0.72, P = 0.47). The subjects in the ChEI-treated group had a marginally, non-significant, higher risk of death due to any cause than those in the placebo-treated group (RR = 1.04, CI(95%) 0.63-1.70, z = 0.16, P = 0.86).
The long-term use of ChEIs in subjects with MCI may attenuate the risk of progression to AD/dementia. This finding may have a significant impact on public health and pharmaco-economic policies.
旨在延缓从轻度认知障碍（MCI）进展为阿尔茨海默病（AD）的胆碱酯酶抑制剂（ChEIs）的个体随机临床试验（RCTs）尚未发现其在此方面使用的显著益处。本研究的目的是对使用ChEIs进行的RCTs进行荟萃分析，以评估汇总分析是否能显示这些药物在延缓从MCI进展为AD方面的益处。
我们在电子数据库（Medline、Embase、科学网和临床试验数据库注册库，特别是Clinicaltrials.gov——http://www.clinicaltrials.gov ）中搜索已发表和未发表研究的参考文献。我们检索到173篇参考文献，从中筛选出3篇用于数据提取。共有来自四项RCTs的3574名受试者纳入荟萃分析。在ChEI治疗组分配的1784名受试者中，275名（15.4%）进展为AD/痴呆，而安慰剂组1790名受试者中有366名（20.4%）进展为AD/痴呆。ChEI治疗组进展为AD/痴呆的相对风险（RR）为0.75 [CI(95%) 0.66 - 0.87]，z = -3.89，P < 0.001。ChEI组患者的全因退出风险显著高于安慰剂组患者（RR = 1.36 CI(95%) [1.24 - 1.49]；z = 6.59，P < 0.001）。ChEI治疗组严重不良事件（SAE）的RR与安慰剂组相比无显著统计学差异（RR = 0.95 [CI(95%) 0.83 - 1.09]，z = -0.72，P = 0.47）。ChEI治疗组受试者因任何原因死亡的风险略高于安慰剂治疗组，但无显著差异（RR = 1.04，CI(95%) 0.63 - 1.70，z = 0.16，P = 0.86）。
在MCI受试者中长期使用ChEIs可能会降低进展为AD/痴呆的风险。这一发现可能对公共卫生和药物经济学政策产生重大影响。
