Ballard C, Sauter M, Scheltens P, He Y, Barkhof F, van Straaten E C W, van der Flier W M, Hsu C, Wu S, Lane R
Wolfson Centre for Age-Related Diseases, King's College, London, UK.
Curr Med Res Opin. 2008 Sep;24(9):2561-74. doi: 10.1185/03007990802328142. Epub 2008 Jul 31.
The aim was to evaluate the efficacy, safety and tolerability of rivastigmine capsules in patients diagnosed with probable vascular dementia (VaD).
VantagE (Vascular Dementia trial studying Exelon) was a 24-week, multicentre, double-blind study. VaD patients aged 50-85 years were randomized to rivastigmine capsules (3-12 mg/day) or placebo. Efficacy assessments included global and cognitive performances, activities of daily living and neuropsychiatric symptoms. Adverse events were recorded. Additional exploratory analyses determined whether heterogeneity in pathologies and symptoms extended to differential treatment effects.
NCT00099216.
710 patients were randomized. Rivastigmine demonstrated superiority over placebo on three measures of cognitive performance (Vascular Dementia Assessment Scale, Alzheimer's Disease Assessment Scale cognitive subscale, Mini-Mental State Examination; all p< or = 0.05, intent-to-treat population [ITT]), but not other outcomes. Predominant adverse events were nausea and vomiting. Exploratory analyses indicated that older patients (> or =75 years old), assumed more likely to also have Alzheimer's disease (AD) pathology, demonstrated significant cognitive responses to rivastigmine and a safety profile similar to that seen in AD patients. Younger patients, assumed less likely to have concomitant AD pathology, showed no efficacy response and were associated with slight elevations of blood pressure, cerebrovascular accidents and mortality. Rivastigmine-placebo differences in patients with, versus those without, medial temporal atrophy (also suggestive of concomitant AD) showed a numerical difference similar to that seen between the older versus younger patients, but did not attain statistical significance.
Consistent with trials evaluating other cholinesterase inhibitors, rivastigmine did not provide consistent efficacy in probable VaD. The efficacy apparent on cognitive outcomes was derived from effects in older patients likely to have concomitant Alzheimer pathology. This is supportive of an existing argument that the putative cholinergic deficit in VaD reflects the presence of concomitant Alzheimer pathology.
评估卡巴拉汀胶囊对确诊为可能的血管性痴呆（VaD）患者的疗效、安全性及耐受性。
VantagE（血管性痴呆试验研究卡巴拉汀）是一项为期24周的多中心双盲研究。年龄在50 - 85岁的VaD患者被随机分为卡巴拉汀胶囊组（3 - 12毫克/天）或安慰剂组。疗效评估包括整体和认知表现、日常生活活动及神经精神症状。记录不良事件。额外的探索性分析确定病理和症状的异质性是否延伸至不同的治疗效果。
NCT00099216。
710例患者被随机分组。在三项认知表现指标上（血管性痴呆评估量表、阿尔茨海默病评估量表认知分量表、简易精神状态检查表；所有p≤0.05，意向性治疗人群[ITT]），卡巴拉汀显示出优于安慰剂的效果，但在其他结局指标上未显示优势。主要不良事件为恶心和呕吐。探索性分析表明，年龄较大（≥75岁）的患者，推测更可能同时患有阿尔茨海默病（AD）病理，对卡巴拉汀有显著的认知反应，且安全性与AD患者相似。年龄较小的患者，推测不太可能有伴随的AD病理，未显示出疗效反应，且与血压轻微升高、脑血管意外及死亡率相关。有内侧颞叶萎缩（也提示伴有AD）的患者与没有内侧颞叶萎缩的患者相比，卡巴拉汀 - 安慰剂差异显示出与老年患者和年轻患者之间相似的数值差异，但未达到统计学显著性。
与评估其他胆碱酯酶抑制剂的试验一致，卡巴拉汀在可能的VaD中未提供一致的疗效。认知结局上明显的疗效源自对可能伴有阿尔茨海默病理的老年患者的作用。这支持了现有的一种观点，即VaD中假定的胆碱能缺陷反映了伴随的阿尔茨海默病理的存在。
