Stroke After High-Dose/Adjuvanted Influenza Vaccines in U.S. Older Adults; 2016-2019

Abstract

ABSTRACTImportanceA recent study from the U.S. Food and Drug Administration investigated the risk of stroke following COVID-19 bivalent and high-dose/adjuvanted influenza vaccines among older adults (individuals ≥65 years) who experienced stroke after vaccination in the 2022-2023 season. The study found a small but significant association between stroke and high-dose/adjuvanted influenza vaccination in the Medicare fee-for-service (FFS) population.ObjectiveTo evaluate stroke risk following high-dose/adjuvanted influenza vaccines in three historical influenza seasons.Design, Setting, and ParticipantsThe analysis included Medicare beneficiaries ≥65 years who had a stroke outcome after receiving a high-dose or adjuvanted influenza vaccine in three influenza seasons 2016-2019. For each season, the study period began on the first Sunday of August and ended one day before the start of the subsequent season (e.g., Sunday, August 7, 2016 through Saturday, August 5, 2017). A self-controlled case series analysis was performed to compare the risk of stroke in risk intervals (1-21 and 22-42 days) to a control interval (43-90 days).ExposuresHigh-dose/adjuvanted influenza vaccines.Main Outcomes and MeasuresNon-hemorrhagic stroke (NHS), transient ischemic attack (TIA), NHS and/or TIA (NHS/TIA), and hemorrhagic stroke (HS).ResultsWe observed 29,730 stroke cases in 2016-2017; 34,518 cases in 2017-2018; and 36,869 cases in 2018-2019. In 2016-2017, the primary analysis found a statistically significant association for HS during the 22-42 day risk window (incidence rate ratio (IRR)=1.14, 95% confidence interval (CI) 1.02–1.28; Risk Difference (RD)/100,000 doses=0.84, 95% CI 0.14−1.54) compared to the control interval. However, no significant primary analysis results were identified in 2017-2018 or 2018-2019.Conclusions and RelevanceWe did not observe clear, consistent evidence of increased stroke risk following high-dose or adjuvanted influenza vaccination across the three seasons 2016-2019. The statistically significant associations we identified were not consistently observed across outcomes, risk windows, age subgroups, or seasons. The clinical significance of any potential risk of stroke following vaccination must be carefully considered together with the significant benefits of receiving an influenza vaccination.