Memantine monotherapy conferred a lower risk for cardiovascular events when compared with acetylcholinesterase inhibitor (AChEI) monotherapy and combination therapy with an AChEI and memantine in elderly patients with Alzheimer’s disease (AD). In addition, there was no difference between treatment groups in the time to admission to a skilled nursing facility (SNF), according to study findings published in JAMA Network Open.

Researchers retrospectively collected claims data from a 5% random sample of Medicare beneficiaries with AD between 2006 and 2014. All patients had received either AChEI monotherapy (donepezil [n=36,463], galantamine [n=1011], rivastigmine [n=6950]), memantine monotherapy (n=11,809), or combination therapy with an AChEI and memantine (n=17,242).

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The primary outcomes included the time to SNF admission, as well as a composite of cardiovascular events (ie, acute myocardial infarction, bradycardia, syncope, atrioventricular block, QT interval prolongation, and ventricular tachycardia).

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With regard to the percentage of patients who were admitted to an SNF, there was no difference between patients starting AChEI monotherapy (25.5%), memantine monotherapy (25.6%), or combination therapy with an AChEI and memantine (29.7%). There was also no difference between patients initiating AChEI monotherapy, memantine monotherapy, AChEI plus memantine with regard to the percentage of patients who experienced ≥1 cardiovascular event (22.2% vs 20.0% vs 24.5%, respectively). No differences were found in time to SNF admission.

In addition, no difference was found between the combination and monotherapy groups in terms of the risk for the composite cardiovascular outcome (adjusted hazard ratio [aHR] 0.99; 95% CI, 0.96-1.03). Compared with memantine monotherapy, a higher risk for the composite cardiovascular outcome was found in patients who received AChEI monotherapy (aHR 1.07; 95% CI, 1.02-1.12) and combination therapy (aHR 1.07; 95% CI, 1.01-1.12).

Patients in the memantine monotherapy group had a lower risk for bradycardia and syncope compared with both the AChEI monotherapy group (aHR 0.88; 95% CI, 0.82-0.95 and aHR 0.92; 95% CI, 0.86-0.97, respectively) and the combination therapy group (aHR 0.89; 95% CI, 0.82-0.97 and aHR, 0.87; 95% CI, 0.83-0.94, respectively).

Limitations of the analysis include its retrospective nature, the inclusion of only Medicare beneficiaries, and the short follow-up duration.

“Leveraging this type of data would enable comparisons of the risk of outcomes between treated and nontreated patients, which would further establish the role of antidementia therapies in the delay of cognitive impairment associated with [Alzheimer disease],” the researchers explained. “If differences in the occurrence of cardiovascular events were confirmed, clinicians may start evaluating cardiovascular safety profiles of the different antidementia medications before prescribing a treatment for their patients.”


San-Juan-Rodriguez A, Zhang Y, He M, Hernandez I. Association of antidementia therapies with time to skilled nursing facility admission and cardiovascular events among elderly adults with Alzheimer disease. JAMA Netw Open. 2019;2(3):e190213.