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Donepezil in Vascular Dementia: Combined Analysis of Two Large-Scale Clinical TrialsRomán G.C.a · Wilkinson D.G.e · Doody R.S.b · Black S.E.f · Salloway S.P.c · Schindler R.J.d
aDepartment of Medicine (Neurology), University of Texas Health Science Center and Audie Murphy Veterans Hospital, San Antonio, Tex., bDepartment of Neurology, Baylor College of Medicine, Houston, Tex., cClinical Neuroscience, Brown Medical School, Providence, R.I., and dPfizer Inc., New York, N.Y., USA; eMemory Assessment and Research Center, Moorgreen Hospital, Southampton, UK; fDepartment of Medicine (Neurology), Sunnybrook and Women’s College Health Sciences Centre, University of Toronto, Toronto, Canada Corresponding Author
Gustavo C. Román, MD
University of Texas Health Science Center, School of Medicine at San Antonio
Department of Medicine, Division of Neurology, Mail Code 7883, 7703 Floyd Curl Drive
San Antonio, TX 78229-3900 (USA)
Tel. +1 210 617 5161, Fax +1 210 567 4659, E-Mail email@example.com
Background and Objective: There are currently no drugs approved to treat vascular dementia (VaD).The objective of this study was to determine if treatment with donepezil, an acetylcholinesterase inhibitor, may provide benefit for VaD patients. Methods: Combined analysis of 2 identical randomized, double-blind, placebo-controlled, 24-week studies involving 1,219 patients enrolled at 109 investigational sites in the USA, Europe, Canada and Australia. Patients were randomized to receive donepezil 5 mg/day (n = 406) or 10 mg/day (after brief titration; n = 421) or placebo (n = 392). Patients were assessed on cognition [Alzheimer’s Disease Assessment Scale – cognitive subscale (ADAS[-]cog), Mini-Mental State Examination (MMSE)], global function [Clinician’s Interview- Based Impression of Change plus (CIBIC[-]plus), Clinical Dementia Rating – Sum of the Boxes (CDR[-]SB)] and function [Alzheimer’s Disease Functional Assessment and Change Scale (ADFACS); instrumental activities of daily living (ADFACS[-]IADL)].Results:Both donepezil groups showed significant improvements in cognition compared with placebo (ADAS-cog, MMSE, p< 0.01). Significant global function benefits were seen on the CIBIC-plus in the 5 mg/day group (placebo vs. 5 mg/day, p < 0.001; vs. 10 mg/day, p = 0.006) and on the CDR-SB in the 10 mg/day group (placebo vs. 5 mg/day, p = 0.09; vs. 10 mg/day, p< 0.01). Significant functional benefits were also seen (ADFACS, placebo vs. 5 mg/day, p = 0.08; vs. 10 mg/day, p = 0.02; ADFACS-IADL, p < 0.05 for both donepezil groups). Donepezil was well tolerated, with low withdrawal rates due to adverse events. Conclusions: This combined analysis of the largest trial on VaD to date showed that donepezil-treated patients had significant benefits in cognition, global function and ability to perform IADL. Based on these findings and reported tolerability, donepezil should be considered as an important therapeutic element in the overall management of patients with VaD.
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