11 Aricept Deaths in Clinical Trial
Excess Deaths in Vascular Dementia Patients Taking Alzheimer's Drug
March 17, 2006 - There were 11 deaths in vascular dementia patients taking the Alzheimer's drug Aricept in a clinical study -- and no deaths in patients taking inactive placebo pills.
The report comes from Aricept maker Eisai Co. Ltd., Tokyo, which sells Aricept in partnership with U.S.-based Pfizer. In the U.S., Aricept is approved for the treatment of mild-to-moderate Alzheimer's disease.
In the trial, there were 11 deaths among 648 vascular dementia patients taking Aricept and zero deaths among 326 patients given placebo in the 24-week study. That's a striking difference. But it may very well be due to a surprisingly low death rate in the placebo group -- and not to any previously unknown risk from Aricept.
No Need for Warning
The FDA is looking at the data but currently finds no reason to issue a warning, says FDA spokeswoman Susan Cruzan.
"FDA is examining the results of the study. We have done a quick review of it and at this point we don't have a major cause of concern," Cruzan tells WebMD. "The drug remains a safe option for patients who are receiving it."
Eisai spokeswoman Judee Shuler notes that the study is the third clinical trial of Aricept in vascular dementia patients. When all three studies are considered together, the death rate among those taking Aricept was 1.7% vs. a 1.1% death rate in placebo recipients. That difference is not statistically significant, meaning it's likely due to chance.
"It is Eisai's position that the results of this study do not change the overall safety profile of Aricept," Shuler tells WebMD. "The safety profile of Aricept continues to be favorable for its approved indication [for mild-to-moderate Alzheimer's disease]."
What Doctors Say
WebMD asked two leading dementia experts what they thought about the Aricept news:
- Sid Gilman, MD, director of the Michigan Alzheimer's Disease Research Center and distinguished professor of neurology at the University of Michigan, Ann Arbor.
- Howard S. Kirshner, MD, professor and vice chairman of neurology at Vanderbilt University in Nashville, Tenn.
Gilman and Kirshner both note that Aricept -- like its sister drugs, Razadyne, Exelon, and Cognex -- increases acetylcholine, a chemical messenger. In the brain, acetylcholine may help memory. But it also may slow down the heart. In the elderly, this increases the risk of potentially deadly heart problems.
Patients with vascular dementia are particularly prone to heart attack and stroke. So while the drugs may very well provide a benefit, they also come with an increased risk. Shuler notes that Aricept did indeed improve mental function in vascular dementia patients, but it did not improve measures of overall function.
Risks vs. Benefits
How much of a benefit is Aricept for Alzheimer's patients? Gilman says it depends on the patient.
"In some patients, there is so little benefit you can't even tell they are on it, and some are very much better," Gilman tells WebMD. "It is very individual. Is it a wonderful, Lazarus-like drug? Heavens no. It does not dramatically alter the course of Alzheimer's disease."
So is taking Aricept worth the risk?
"If people are on Aricept for Alzheimer's disease, I would reassure them we haven't seen any evidence of excess death," Kirshner tells WebMD. As far as vascular dementia goes, it is a little tricky. It is very common to have vascular dementia mixed with Alzheimer's disease. And I don't think we should shy away from [Aricept and similar drugs] in that group."