Association of Antidementia Therapies With Time to Skilled Nursing Facility Admission and Cardiovascular Events Among Elderly Adults With Alzheimer Disease

Abstract

Importance: To date, no study has compared time to skilled nursing facility (SNF) admission and cardiovascular events across medications available to treat Alzheimer disease. Objective: 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 in treating elderly adults with Alzheimer disease. Design, Setting, and Participants: This retrospective cohort study uses January 1, 2006, to December 31, 2014, claims data from a 5% random sample of Medicare beneficiaries who had received a new diagnosis of Alzheimer disease between January 1, 2007, and December 31, 2013, and who initiated AChEI monotherapy, memantine monotherapy, or combination therapy with an AChEI and memantine (N = 73 475). Patients were followed up until discontinuation of treatment, switch of treatment, death, or the end of the study period. Statistical analysis was conducted from February 15, 2018, to June 15, 2018. Exposures: Acetylcholinesterase inhibitor monotherapy (n = 44 424), memantine monotherapy (n = 11 809), and combination therapy with an AChEI and memantine (n = 17 242). Main Outcomes and Measures: Primary outcomes were 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. Cox proportional hazards regression models were constructed to compare outcomes between each pair of treatment groups, controlling for a comprehensive list of patient characteristics. Results: The study population included 73 475 participants (53 068 women and 20 407 men; mean [SD] age, 81.8 [8.3] years); 25.5% of the participants initiating AChEI monotherapy, 25.6% of participants initiating memantine monotherapy, and 29.7% of participants initiating combination therapy with an AChEI and memantine were admitted to an SNF. Similarly, 22.2% of the participants initiating AChEI monotherapy, 20.0% of those initiating memantine monotherapy, and 24.5% of those initiating combination therapy experienced at least 1 cardiovascular event. No difference in time to SNF admission was found across the 3 treatment groups. The risk of the composite measure of any cardiovascular event did not differ between the combination therapy and AChEI monotherapy groups (adjusted hazard ratio [aHR], 0.99; 95% CI, 0.96-1.03); however, it was higher for both AChEI monotherapy (aHR, 1.07; 95% CI, 1.02-1.12) and combination therapy (aHR, 1.07; 95% CI, 1.01-1.12), relative to memantine monotherapy. This result was mainly driven by the lower risk of bradycardia and syncope observed for the memantine monotherapy group relative to both AChEI monotherapy (bradycardia: aHR, 0.88; 95% CI, 0.82-0.95; and syncope: aHR, 0.92; 95% CI, 0.86-0.97) and combination therapy (bradycardia: aHR, 0.89; 95% CI, 0.82-0.97; and syncope: aHR, 0.87; 95% CI, 0.83-0.94). Conclusions and Relevance: 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.