Donepezil not associated with increased risk of proarrhythmic cardiac events

Assessing the risks and benefits of donepezil just got easier thanks to findings from a new study. A systemic review of randomized clinical trials found no increased risk of major adverse cardiac events associated with QT interval prolongation in people taking donepezil compared to those on placebo.Donepezil’s product monograph states that there have been after-market reports of long QT syndrome and other cardiac events. It’s classified as a “known risk” QT interval-prolonging medication (QTPmed), even though much of the evidence is from observational data, including single case reports, according to the authors of the review.Researchers from McMaster University and the University of Toronto performed a systematic review with meta-analysis of 60 clinical trials involving 12,463 participants randomized to donepezil or placebo. There was no increased risk of major adverse cardiac events (MACE) for people taking donepezil compared to those taking placebo. MACE was defined as mortality, sudden cardiac death, non-fatal cardiac arrest, Torsades de points, ventricular tachyarrhythmia, seizure or syncope. None of these individual outcomes were statistically different between the two groups, suggesting no increased risk of events associated with QT interval prolongation such as ventricular arrhythmias, seizures or syncope.Read: ‘Risk factors’: Study suggests severe menopausal symptoms linked to dementia“We found there was no association between donepezil and this specific fatal heart condition,” says Dr. Tina Nham, co-lead author of the study 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,” Dr. Nham said in a press release.More research is needed to determine the safety of donepezil in those with existing heart disease, the authors note.The findings might help ease the administrative burden on physicians and others using EMRs, Dr. Nham and colleagues note. If warning labels about donepezil and QT interval heart arrhythmias are dropped, this could mean less clicking for those who prescribe or dispense the medication.“Clinicians get a huge amount of these warnings on the EMRs that we use. Studies show the amount of clicking that we have to do to override these warnings can lead to things like caregiver burnout and caregiver stress,” Dr. Nham said.The majority of donepezil’s adverse events are gastrointestinal, such as nausea, diarrhea or loss of appetite.“Unfortunately, our current drug therapies for dementia, including donepezil, fall far short on important outcomes like keeping patients functioning at home with their families, but at least the heart arrhythmia concern and its related death or syncope (fainting) does not seem to be an important problem,” said Dr. Anne Holbrook, senior author and a professor with McMaster University’s department of medicine and director of the division of clinical pharmacology and toxicology.The paper was published in The Journal of the American Geriatrics Society.Read: New Canadian guidelines outline how to assess and manage anxiety in older adults

Donepezil not associated with increased risk of proarrhythmic cardiac events

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