Risk of stroke associated with risperidone in dementia with and without comorbid cardiovascular disease: population-based matched cohort study

Background: Agitation and aggression occur in up to half of people living with dementia over the course of the disease. While non-pharmacological interventions are first line treatment strategies, in severe cases associated with a risk of harm, antipsychotics may be indicated. A major adverse effect of antipsychotics in dementia is an increased risk of stroke and the atypical antipsychotic risperidone’s mechanism of action has been linked to cardiovascular disease (CVD) biological pathways. Aims:To evaluate the risk of stroke associated with risperidone use across different patient subgroups defined by stroke and CVD history.Method:Anonymised primary care data from the UK-based Clinical Practice Research Datalink (CPRD) was used to identify individuals diagnosed with dementia after the age of 65 between 2004 and 2023. Risk of stroke over one year was compared between individuals initiating risperidone and propensity score-matched controls.Results: In the overall cohort (28,403 Risperidone Users and 136,324 Matched Controls), patients treated with risperidone had an increased risk of stroke (adjusted hazard ratio (HR): 1.28; 95% confidence interval (CI): 1.20-1.37). In the Risperidone User group, the incidence rate (IR) of stoke was substantially higher in those with a prior history of stroke (IR: 222 per 1000 person-years (PY)) and CVD (IR: 94.1 per 1000 PY) than in the overall cohort (IR: 53.3 per 1000 PY). Relative risks related to risperidone were similar across all CVD and stroke subgroup comparisons (HRs between 1.23 and 1.44). Conclusions:People with dementia with a prior history of CVD are at a significant increased risk of stroke and risperidone further exacerbates this risk. Moreover, risperidone also increases risk of stroke in patients without a prior history of CVD. This quantification of stroke risk across subgroups with and without history of CVD may help with communication risk and aid more judicious prescribing.