Alvaro San-Juan-Rodriguez

Alzheimer Disease Medications: Progression to Nursing Home & Cardiac Side Effects Interview with:

Alvaro San-Juan-Rodriguez

Alvaro San-Juan-Rodriguez

Alvaro San-Juan-Rodriguez, PharmD
Pharmacoeconomics, Outcomes and Pharmacoanalytics Research Fellow
Pharmacy and Therapeutics
School of Pharmacy
University of Pittsburgh What are the main findings?

Response: Currently, there are 4 antidementia drugs approved by the FDA for the treatment of Alzheimer’s disease, including 3 acetylcholinesterase inhibitors (AChEIs)—donepezil, rivastigmine, and galantamine—and the N-methyl-D-aspartic receptor antagonist memantine. On the one hand, evidence about the effect of these drugs at delaying nursing home admission is still sparse and conflicting. On the other, all these antidementia medications have been associated with several cardiovascular side effects, such as bradycardia, ventricular tachycardia, syncope, QT interval prolongation, atrioventricular block or even myocardial infarction.

In this study, we aimed to compare time to nursing home admission and time to cardiovascular side effects across all drug therapies available for the treatment of Alzheimer’s disease. In doing so, we used 2006-2014 medical and pharmacy claims data from Medicare Part D beneficiaries with a new diagnosis Alzheimer’s disease who initiated antidementia drug therapy. What is the background for this study?

Response: Our study yielded two major results.

First, we found no differences across treatments in terms of time to nursing home admission. In other words, no treatment performed better than any other in delaying the admission into a nursing home.

Second, AChEI monotherapy and combination therapy with an AChEI and memantine were associated with a 7% higher risk of cardiovascular side effects relative to memantine monotherapy. This higher risk of cardiovascular side effects was mainly driven by a higher risk of bradycardia and syncope observed for AChEI monotherapy and combination therapy compared to memantine monotherapy. What should readers take away from your report? 

Response: Our study has an important clinical implication.

We found that both AChEI monotherapy and combination therapy are associated with an increased risk of cardiovascular side effects compared to memantine monotherapy. However, this increased risk resulted from a higher risk of bradycardia (slow heart rate) and syncope (fainting), which are not as severe or life threatening as other of the cardiovascular side effects assessed in this study. Thus, the clinical significance and impact on patients’ outcomes of this increased risk remains still uncertain. If differences in the incidence of cardiovascular side effects were confirmed, clinicians could start evaluating cardiovascular safety profiles of the different antidementia medications before prescribing a treatment for their patients. What recommendations do you have for future research as a result of this work?

Response: Future studies should assess clinical, functional, and utilization outcomes of patients with Alzheimer’s disease who are experiencing bradycardia or syncope to clarify the clinical significance of our observations and answer some unresolved questions, such as: what happen to those patients who experienced bradycardia or syncope? Were they more likely to fall? Were they more likely to get a bone fracture? In addition, further research should validate these findings in other cohorts of patients, using data that better capture cognitive, behavioral, and psychological function. Leveraging this type of data would enable comparisons of the risk of effectiveness and safety outcomes between those patients who initiated antidementia drug therapy and those who did not, which would contribute to elucidate the actual role of antidementia medications in real-world patients with Alzheimer’s disease.


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. doi:10.1001/jamanetworkopen.2019.0213

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Last Updated on March 1, 2019 by Marie Benz MD FAAD