April 23, 2019
By Julie Gould
According to research published online in JAMA Network Open, the time to skilled nursing facility (SNF) admission does not differ across approved medications used to treat Alzheimer disease (AD). However, memantine hydrochloride monotherapy was associated with a lower risk of cardiovascular events.
In order to compare time to SNF admission and cardiovascular events between acetylcholinesterase inhibitor (AChEI) monotherapy, memantine hydrochloride monotherapy, and combination therapy with an AChEI and memantine among older adults with AD, a retrospective study was conducted. The study, led by Alvaro San-Juan-Rodriguez, PharmD, Department of Pharmacy and Therapeutics at the University of Pittsburgh, and colleagues, aimed to determine “time to SNF admission and the composite of the following cardiovascular events: acute myocardial infarction, bradycardia, syncope, atrioventricular block, QT interval prolongation, and ventricular tachycardia.”
According to the findings, “Time to SNF admission did not differ across treatment groups, but memantine monotherapy was associated with a lower risk of cardiovascular events compared with both AChEI monotherapy and combination therapy with an AChEI and memantine.”
In order to better understand why clinicians should evaluate the risk-benefit profile of the different antidementia medications and individualize their prescribing patterns based on their patients’ characteristics, Annals of Long-Term Care spoke with study author Inmaculada Hernandez, PharmD, PhD, assistant professor of pharmacy and therapeutics at the University of Pittsburgh School of Pharmacy.
Please tell us a little about yourself and your research interests
My research interests revolve around pharmaceutical health services and outcomes research, pharmacoepidemiology, pharmacoeconomics and pharmaceutical policy. More specifically, my research has recently focused in three main areas: 1) use of large data sets, advanced data mining techniques and comparative effectiveness research to predict and compare outcomes of antidementia medications; 2) real-world use and outcomes of oral anticoagulation therapy in stroke prevention in atrial fibrillation; and 3) pharmaceutical pricing trends and pricing strategies in response to market disruptions.
Briefly highlight the objective of your study and identify why it was important to conduct.
In this study, we aimed to compare time to skilled nursing facility admission and cardiovascular events across all available drug therapies for the treatment of Alzheimer’s disease. Specifically, acetylcholinesterase inhibitor monotherapy, memantine monotherapy, and combination therapy with an acetylcholinesterase inhibitor and memantine. There is a growing body of evidence showing a limited efficacy of antidementia medications at keeping patients longer in the community and an association between the use of antidementia medications and the incidence of various cardiovascular events. Yet, no study had compared these outcomes across all the available pharmacological strategies. This study is an important contribution because is the first to compare time to skilled nursing facility admission and cardiovascular events across all available drug therapies for the treatment of Alzheimer’s disease.
Currently there are 4 FDA-approved antidementia drugs. How often are patients admitted to a SNF taking one of these drugs? How often do patients, who are prescribed these drugs, experience cardiovascular events?
Our study found that—among Medicare beneficiaries who were newly diagnosed with Alzheimer’s disease and who initiated any antidementia medication—26.6% were admitted into a to skilled nursing facility during follow-up. Similarly, 22.7% experienced at least one cardiovascular event during follow-up. It is important to note that bradycardia and syncope were the most frequently experienced cardiovascular events (9.0% and 13.0%, respectively). These events are relatively milder compared to other of the studied cardiovascular events such as myocardial infarction.
Based on your study findings, how does time to a SNF and cardiovascular events compare for patients with newly diagnosed AD?
We found that time to skilled nursing facility admission did not differ across the different treatment groups; however, the acetylcholinesterase inhibitor monotherapy and the combination therapy groups were associated with a 7% higher risk of any cardiovascular event compared with the memantine monotherapy group. This higher risk of any cardiovascular event was mainly driven by the higher risk of bradycardia and syncope observed for both acetylcholinesterase inhibitor monotherapy and combination therapy compared to memantine monotherapy.
What knowledge gaps still exist between SNF admission and cardiovascular event risk among this patient population?
There are still several gaps in the literature regarding the use of antidementia medications among elderly adults and the risk of skilled nursing facility admission and incidence of cardiovascular events. More importantly, it is critical to determine what patient characteristics contribute the most toward an increased risk of skilled nursing facility admission and incidence of cardiovascular events. Additionally, it would be necessary to assess if there exists any subgroup of patients for which the benefits of a particular antidementia drug therapy outweigh the risks.
What can clinicians take away from your study?
Acetylcholinesterase inhibitors are likely to increase the risk of bradycardia and syncope. Additionally, there is limited evidence about efficacy of antidementia medications, especially as Alzheimer’s disease progress into the moderate and severe stages. Clinicians should evaluate the risk-benefit profile of the different antidementia medications and individualize their prescribing patterns based on their patients’ characteristics. Some of these characteristics may be the stage of the disease and other factors contributing toward a higher risk of bradycardia and syncope, such as the use of antihypertensives or tricyclic antidepressants. In any case, there should be an increased awareness about the potential risk of bradycardia and syncope associated to acetylcholinesterase inhibitors.
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 [published online March 1, 2019]. JAMA Netw Open. 2019;2(3):e190213. doi:10.1001/jamanetworkopen.2019.0213