(P-002) Risk of First Ischemic Stroke and Use of Antidopaminergic Antiemetics: A Case-time-control Study in France

Background: The risk of stroke with antidopaminergic antipsychotics is well-known, especially in elderly patients and patients with dementia. So far, this risk has not been assessed for antidopaminergic antiemetics (ADA), widely used in general practice.

Objectives: To estimate the risk of first ischemic stroke associated with ADA use.

Methods: A case-time-control study was performed using data from the French reimbursement healthcare system (SNDS). All patients ≥18y registered in the database with a first ischemic stroke between 2012 and 2016, and at least one reimbursement for any ADA (domperidone, metoclopramide, metopimazine) in the 70 days before stroke occurrence were included. Exclusion criteria were: history of cancer, use of fixed association metoclopramide-aspirin, hospitalisation in the 70 days before stroke. To estimate the association within each patient, frequency of ADA reimbursements was compared between a risk period (days [-14, -1] before stroke) and 3 matched reference periods (days [-70, -57], [-56, -43], and [-42, -29] before stroke). The conditional logistic model used considered as time-varying confounders the use of prothrombotic or vasoconstrictive drugs, anticoagulants, and antiplatelets. Time-trend of ADA use was controlled using a control group of randomly selected patients free of the event, individually matched to cases according to age, sex, and risk factors of stroke. Controls were recruited at the same time as the stroke cases. The ratio of adjusted ORs (stroke cases aOR divided by control aOR) yielded an estimate of the effect of ADA use on risk of stroke.

Results: We included 2,778 ischemic stroke cases exposed to ADA. Median age was 76 years (interquartile range 63 to 85) and 34.4% were men. Among cases, 1,333 and 1,134 were exposed to ADA in the risk and reference periods, respectively. The comparison with the 5,957 and 15,472 controls exposed to ADA in the same periods yielded a ratio of aORs of 3.16 (2.90 to 3.45). A sensitivity analysis using 7-day periods (risk and reference) showed a higher risk of 4.56 (4.04 to 5.10). Analyses stratified on age ( <70y, ≥70y), sex, and dementia showed similar results. Ratio of aORs for analyses stratified on drug was 2.47 (2.17 to 2.82) for domperidone, 3.40 (2.94 to 3.93) for metopimazine, and 4.47 (3.39 to 5.89) for metoclopramide.

Conclusions: Using French nationwide exhaustive reimbursement data, this self-controlled study reported an increased risk of ischemic stroke with recent ADA use. This risk appeared higher in the first days of use. All ADA were associated with an increased risk, the highest increase being highlighted for metoclopramide.