Page 44 - Drug Class Review

Final Report Update 1 Drug Effectiveness Review Project

Evidence from a recently published large-scale placebo-controlled study supports the general efficacy of
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rivastigmine in treating patients with PD dementia. This 24-week multicenter European study enrolled
541 subjects with PD dementia (defined as the onset of cognitive symptoms 2 or more years after the
onset of PD) who were randomized to either placebo or rivastigmine (1:2 ratio) beginning at 1.5mg twice
a day and increased at 4-week intervals as tolerated up to 12 mg/day. Primary efficacy analyses showed

better ADAS-cog scores and global ratings in the rivastigmine-treated group compared to placebo group.

E. Comorbid vascular dementia

Vascular dementia is the second most common form of dementia. In many patients with AD, vascular
factors contribute to the development or expression of dementia. Mixed vascular dementia includes those

patients that have clinical features of AD and clinically significant cerebrovascular disease. Most studies
included in our review specifically excluded patients with mixed vascular dementia; studies that did not

explicitly exclude patients with comorbid cerebrovascular disease often did not report the prevalence or
stratify the results for this subgroup.

Although evidence is difficult to interpret given the inconsistencies in trial design and lack of
differentiation between AD and vascular dementia, we discuss four studies that provide general evidence
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of the efficacy of donepezil, galantamine, rivastigmine, and memantine in populations with
comorbid vascular dementia.

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The only effectiveness study included in our review randomized patients with or without a coexisting
diagnosis of vascular dementia to long-term treatment with donepezil or placebo. Although results are
not stratified by coexisting vascular dementia, results support the general efficacy of donepezil in this

mixed population.

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One placebo-controlled RCT examined the effect of galantamine in patients with probable vascular
dementia and AD with cerebrovascular disease. This 26-week trial randomized 592 patients to
galantamine or placebo in a 2:1 ratio. Diagnosis of vascular dementia was based on National Institute of

Neurological Disorders and Stroke and the Association Internationale pour la Recherche et
l’Enseignement en Neurosciences (NINDS-AIREN) International Workshop criteria; computed
tomography or magnetic resonance imaging was used to confirm evidence of cerebrovascular disease.

Overall, galantamine was significantly better than placebo (P < 0.05) on cognitive, functional, behavioral,
and global assessment measures. Treatment differences were of similar size to those seen in galantamine

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