Galantamine treatment of vascular dementia: a randomized trial
Auchus AP, Brashear HR, Salloway S, Korczyn AD, De Deyn PP, Gassmann-Mayer C; GAL-INT-26 Study Group;
Commented by , 11 Sep 2007
Aim of the study
To evaluate the efficacy and safety of the cholinesterase inhibitor (CI) galantamine for patients with vascular dementia (VaD) in mild to moderate stages.
Method
Multinational, randomized, double-blind, parallel-group trial comparing galantamine 16 or 24 mg/day (based on tolerability) to placebo over 26 weeks. The diagnostic criteria for "probable VaD" were those of the NINDS-AIREN, with central reading of brain MRI done within 12 months of participation in this study.
The severity range was determined by a Mini Mental State Examination (MMSE) score of 10 to 26 and an Alzheimer's Disease Assessment Scale – cognitive subscale 11 items (ADAS-cog/11) score of 12 or more.
The primary efficacy measures were the ADAS-cog/11 and the Alzheimer's Disease Cooperative Study – Activities of Daily Living Inventory 23 items (ADCS-ADL). Secondary efficacy measures were the Clinician's Interview Based Impression of Change-Plus Caregiver Input (CIBIC-plus), the Neuropsychiatric Inventory 10 items (NPI), the executive test 25 items EXIT-25, and different variations of the ADAS-cog. Safety and tolerability were monitored.
Results
The majority of the 788 patients enrolled had Hachinski Ischemic Score of 7 or above and were men, with a mean MMSE score of 20. There was a statistically significant greater improvement in ADAS-cog/11 after 26 weeks on galantamine compared to placebo (-1.8 vs -0.3; p < 0.001).
There was no difference on the ADCS-ADL score (0.7 vs 1.3; p = 0.783). Improvement in global functioning measured by the CIBIC+ associated with galantamine approached significance (p = 0.069). A statistically significant difference favoring galantamine was found using EXIT-25 (p = 0.041).< /p > < p > Safety data revealed that 13% of patients on galantamine and 6% on placebo discontinued treatment because of adverse events. There was no difference on NPI total score between the two treatment groups, the starting score being low (10.9 and 12.4). Five deaths occurred on galantamine and ten on placebo during or within 30 days after the study.
Professor Gauthier's comments
This population of patients with VaD was clearly different from patients with similar severity of dementia caused by Alzheimer's disease (AD): more men than women, and improvement above baseline in both galantamine and placebo groups for both cognitive and functional measures.
The statistical difference favoring galantamine on the ADAS-cog/11 and the EXIT-25 is thus driven by improvement on galantamine and not by decline on placebo (which is often the case in AD). The stability of the placebo groups in VaD over 26 weeks has been described before and can be explained to a great extent by the strict control of vascular risk factors such as arterial hypertension, diabetes mellitus, metabolic syndrome, atrial fibrillation, in a clinical trial setting.
Furthermore there can be improvement from stroke recovery, through brain plasticity and rehabilitation.
The meta-analysis published by Kavirajan and Schneider (ref. 1) included this study in their analysis. Their conclusions are that the data overall for CI and memantine does not support a widespread use of these drugs in VaD, but there are individual patients who might benefit.
References
1. Kavirajan H, Schneider LS. Efficacy and adverse effects of cholinesterase inhibitors and memantine in vascular dementia: a meta-analysis of randomised controlled trials. Lancet Neurology 2007; 6 (9); 782-792