Eleven of 648 patients died while taking donepezil (Aricept) in a trial of the drug for the treatment of vascular dementia, according to preliminary study results announced by Eisai Co. Ltd., the drug's maker. None of the 326 patients taking placebo during the 24-week trial died.
The multicenter, randomized, double-blind study was conducted in nine countries and enrolled only people with vascular dementia (VaD), who had no prior diagnosis of Alzheimer's disease. Donepezil is currently approved only for the treatment of mild to moderate Alzheimer's disease in the United States.
Those patients taking donepezil showed improvement on measures of cognition, compared with those on placebo. However, there was no benefit observed on global function, the trial's other primary measure.
An analysis of adverse events data revealed that the mortality rate of 1.7% for the donepezil treatment group in this trial was consistent with that observed in a combined analysis of two previous VaD studies (1.7%) and was lower than that reported in the general population of patients with vascular dementia. However, the mortality rate observed in the placebo group of this study (0%) was lower than that seen in the placebo groups in the combined analysis for the two prior VaD studies (2%), and was lower than the rate for the general VaD population.
In an analysis of all three vascular dementia trials, observed mortality rates were not statistically significant between the donepezil-treated group and the placebo group (1.7% vs. 1.1%).
Additional analyses of vascular events such as stroke and myocardial infarction for the three VaD trials, alone and combined, showed a statistically significant higher risk of a vascular event in the donepezil group, compared with placebo.
In the most recent study, overall adverse events were not significantly different between the treatment and placebo groups. Adverse events in the treatment group occurred at a rate greater than 5%, and twice the rate of placebo, for abdominal pain (5.1% vs. 2.5%), anorexia (5.7% vs. 2.8%), and nausea (9.9% vs. 4.3%).
Eisai has notified regulatory authorities about the mortality findings, and has reported that the results of the most recent vascular dementia study have not changed the overall safety profile of the drug, and that the drug's benefit-risk profile continues to be favorable for its approved indications.