Abstract
BackgroundThe effect of antipsychotic (AP) drugs on risk of stroke and myocardial infarction (MI) remains unclear due to methodological limitations of, and inconsistencies across, existing studies. We aimed to systematically review studies reporting on the associations between AP drug use and stroke or MI risk, and to investigate whether associations differed among different sub-populations.MethodsWe searched Medline, EMBASE, PsychINFO and Cochrane Library (from inception to May 28, 2017) for observational studies reporting on AP drug use and MI or stroke occurrence. We performed random-effects meta-analyses for each outcome, performing sub-groups analyses by study population – specifically general population (i.e. those not restricted to patients with a particular indication for AP drug use), people with dementia only and psychiatric illness only. Where feasible we performed subgroup analyses by AP drug class.ResultsFrom 7008 articles, we included 29 relevant observational studies, 19 on stroke and 10 on MI. Results of cohort studies that included a general population indicated a more than two-fold increased risk of stroke, albeit with substantial heterogeneity (pooled HR 2.31, 95% CI 1.13, 4.74, I2 = 83.2%). However, the risk among patients with dementia was much lower, with no heterogeneity (pooled HR 1.16, 95% CI 1.00, 1.33, I2 = 0%) and there was no clear association among studies of psychiatric populations (pooled HR 1.44, 95% CI 0.90, 2.30; substantial heterogeneity [I2 = 78.8])). Associations generally persisted when stratifying by AP class, but few studies reported on first generation AP drugs. We found no association between AP drug use and MI risk (pooled HR for cohort studies: 1.29, 95% CI 0.88, 1.90 and case-control studies: 1.07, 95% CI 0.94, 1.23), but substantial methodological and statistical heterogeneity among a relatively small number of studies limits firm conclusions.ConclusionsAP drug use may be associated with an increased risk of stroke, but there is no clear evidence that this risk is further elevated in patients with dementia. Further studies are need to clarify the effect of AP drug use on MI and stroke risk in different sub-populations and should control for confounding by indication and stratify by AP drug class.
Highlights
The effect of antipsychotic (AP) drugs on risk of stroke and myocardial infarction (MI) remains unclear due to methodological limitations of, and inconsistencies across, existing studies
Earlier reviews focused on summarizing the effects of AP drug use in the elderly or those with dementia [10, 20], the most recent of which suggests that AP drug use may be associated with an increased risk of stroke in this population [20]
Inclusion and exclusion criteria We sought studies that included a general population or people with specific mental disorders often treated with AP drugs, and compared AP drug use versus no AP drug use in relation to risk of stroke or MI
Summary
The effect of antipsychotic (AP) drugs on risk of stroke and myocardial infarction (MI) remains unclear due to methodological limitations of, and inconsistencies across, existing studies. Prescription medication, including antipsychotic (AP) drug use, has been raised as a possible cardiovascular and cerebrovascular disease risk factor, potentially operating through effects on body weight, metabolic factors and thrombosis [10] Despite their potential to increase risk of circulatory disease, AP drugs are being increasingly used offlabel, for the treatment of dementia, anxiety, insomnia and post-traumatic stress [11], with little understanding of the long-term side-effects, including risks of major cardiovascular events such as myocardial infarction and stroke. Their increased use in patients with dementia is concerning, with around 20% of patients with dementia in nursing homes in the USA and UK treated with APs [12, 13]. Confirmation of the appropriateness of these attached warnings to AP drug use is important, given that pharmacological alternatives for the treatment of behavioral and psychological symptoms of dementia are quite limited [18]
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