Researchers at the McMaster University, in a new meta-analysis, have found that donepezil, a medication commonly prescribed for dementia does not increase the risk of death and certain heart rhythm problems, contrary to past warnings. The research, published in the Journal of the American Geriatrics Society, noted that past warnings of this class of drugs called cholinesterase inhibitors (ChEIs) are classified as a “known risk” QT interval-prolonging medication (QTPmed). However, they note this claim only has been derived from observational data including single case reports.
“We aimed to evaluate high-quality literature on the frequency and nature of proarrhythmic major adverse cardiac events (MACE) associated with donepezil,” the researchers wrote.
Donepezil has more than six million prescriptions issued in 2020 in the United States. It is prescribed to slow down the progression of dementia symptoms, such as memory loss, but there has remained doubts over its effectiveness. In addition, the drug can cause a range of side effects including nausea, loss of appetite, urinary symptoms, and diarrhea.
The McMaster investigators conducted their analysis to determine if patients prescribed this drug were more prone to developing fatal heart arrhythmias related to the QT interval, the amount of time it takes the heart’s electrical system spur a heartbeat and then reset as compared with people not on the medication.
The investigators queried Medline, Embase, International Pharmaceutical Abstracts, and Cochrane Central from 1996 to today to identify randomized controlled trials involving patients over the age of 18 that compared donepezil to placebo. The team developed a MACE composite score that included mortality, sudden cardiac death, non-fatal cardiac arrest, Torsades de pointes, ventricular tachyarrhythmia, seizure or syncope.
In total, the researchers analyzed 60 randomized clinical trials that included more than 12,000 people.
In this more detailed analysis of published research, “we found there was no association between donepezil and this specific fatal heart condition,” says Tina Nham, co-lead author and a fifth-year geriatric medicine resident with McMaster University’s Department of Medicine. “It’s good for prescribers to know that donepezil may not be as high of a risk for this fatal arrhythmia as previously thought. For patients who are taking donepezil, there is a fear that it can lead to several bad side-effects on the heart and this review helps demystify some of those long-held beliefs.”
The investigators say this meta-analysis was necessary as some previous studies that have warned about these specific health risks of donepezil were lacking due to the inclusion of a very small number of people, or not having a proper comparison group.
While noting that the current crop of dementia medications, including donepezil, generally don’t provide significant improvements in patient outcomes such as keeping people function in their homes, the researchers note that these findings should alleviate concerns about increasing heart arrhythmia and deaths related to it.
“These reviews are so important in demystifying preconceived risks associated with medications like donepezil,” said co-lead author Cristian Garcia, a medical student at the University of Toronto’s Temerty Faculty of Medicine. “We’re able to question the prior quality of evidence and ask why things are the way they are. We’re able to dig into a deep pool of reliable evidence and provide patients and clinicians with some reassurance.”
