Antipsychotics and the Risk of Myocardial Infarction in Elderly with Dementia
Abstract & Commentary
By Rahul Gupta, MD, MPH, FACP, Clinical Assistant Professor, West Virginia University School of Medicine, Charleston, WV. Dr. Gupta reports no financial relationships relevant to this field of study.
Synopsis: Antipsychotic drug use may increase the risk of myocardial infarction in elderly patients with dementia.
Source: Pariente A, et al. Antipsychotic use and myocardial infarction in older patients with treated dementia. Arch Intern Med 2012;172:648-653.
In patients 65 years of age and older, most dementias are attributable to Alzheimer's disease. Currently, 5.4 million Americans are living with Alzheimer's disease. However, this population is expected to nearly triple over the next 40 years, reaching approximately 14.5 million. Alzheimer's disease is the sixth leading cause of death in the United States and the fifth leading cause of death in Americans aged 65 years and older. Since it is the only cause of death among the top 10 in the United States that cannot be prevented, cured, or even slowed, deaths attributable to Alzheimer's dementia have been rising dramatically, while other major causes of death have been on the decline.1
Advancing dementia is often accompanied by agitation, delusions, and hallucinations. Antipsychotic agents are often prescribed to control these symptoms. Research demonstrates that nearly one-third of elderly nursing home residents with dementia receive antipsychotic medications and more than one in five elderly nursing home residents with dementia use medications with marked anticholinergic side effects. Evidence also suggests that elderly patients with dementia may be more susceptible to developing antipsychotic medication-related adverse effects. Studies have shown that the use of both conventional and atypical antipsychotics is linked with increased risk of stroke.2 Further research has also demonstrated that antipsychotic use is associated with an increased risk for death compared with nonuse among older adults with dementia.3 The risk for death may be greater with conventional antipsychotics than with atypical antipsychotics. However, the FDA's black box advisory has been associated with decreases in the use of such antipsychotics, especially among elderly patients with dementia. Since major cardiovascular events were one of the primary causes of increased deaths, it is important to examine the relationship of antipsychotic use and myocardial infarction in this population.
In their study, Pariente et al conducted a retrospective cohort study of community-dwelling older patients (≥ 66 years) in Quebec who had initiated cholinesterase inhibitor treatment between January 1, 2000, and December 31, 2009. Using statistical analysis, users and nonusers of the antipsychotics were matched and risk for acute myocardial infarction was evaluated. The researchers found that approximately 29.5% of dementia patients were started on antipsychotic medications. Atypical antipsychotics accounted for 97.8% of the medications (risperidone, quetiapine fumarate, and olanzapine). Within 1 year of being on the antipsychotic medications, 1.3% of patients suffered a myocardial infarction. The risk was highest within the first 30 days of initiation. In the retrospective cohort study, the hazard ratios for myocardial infarction among antipsychotic users relative to nonusers were 2.19 for the first 30 days, 1.62 for the first 60 days, 1.36 for the first 90 days, and 1.15 for the first 365 days.
Commentary
The findings by Pariente et al demonstrate that the use of antipsychotic medication in the elderly population with dementia is associated with a modest increase in the risk of myocardial infarction. Since this study was limited to community-dwelling seniors, no data are available for long-term care individuals, although it is difficult to imagine that the results would differ significantly. While the authors were unable to differentiate the effects of atypical and conventional antipsychotics, it is also fair to assume that there may not be much difference based on the known effects of these drugs on stroke and overall mortality.
While the use of antipsychotic medications in the elderly population and especially in those with dementia remains of significant concern and has been the subject of a cautionary tale for prescribers, it is somewhat disappointing to observe that almost a third of dementia patients (29.5%) were still being prescribed antipsychotics in the study population. Sufficient published data on the effect of antipsychotics in elderly patients with dementia provide little support for their use in routine practice. In fact, studies have consistently demonstrated that antipsychotic use by elderly individuals with dementia is associated with increased risk of death by approximately 30%, regardless of the use of conventional or atypical types of medication.4 It is important to note in this study that rather than progressively incremental, the risk of myocardial infarction was found to be the highest within the first 30 days of initiating such a treatment. Therefore, it may be noteworthy that when antipsychotic therapy cannot be avoided, it is imperative to conduct a comprehensive cardiac risk assessment, discuss such risks with the patient and caregivers, and closely monitor the patient for several weeks upon initiation of the treatment.
References
1. Alzheimer's Association, Thies W, Bleiler L. 2011 Alzheimer's disease facts and figures. Alzheimers Dement 2011;7:208-244.
2. Douglas IJ, Smeeth L. Exposure to antipsychotics and risk of stroke: Self controlled case series study. BMJ 2008;337:a1227.
3. Wang PS, et al. Risk of death in elderly users of conventional vs. atypical antipsychotic medications. N Engl J Med 2005;353:2335-2341.
4. Gill SS, et al. Antipsychotic drug use and mortality in older adults with dementia. Ann Intern Med 2007;146:775-786.
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