(362) Stroke Risk Following Receipt of High-Dose/Adjuvanted Influenza Vaccinations Among U.S. Adults Aged ≥65 Years; 2016-2019

Background: A recent study by the U.S. Food and Drug Administration detected a small but statistically significant association between stroke and high-dose/adjuvanted influenza vaccination in the Medicare fee-for-service (FFS) population ≥65 years in 2022-2023.

Objectives: To determine if an increase in stroke risk occurred following high-dose/adjuvanted influenza vaccination in Medicare beneficiaries in three historical influenza seasons: 2016-2017, 2017-2018, 2018-2019.

Methods: The study was conducted using Medicare FFS claims data from August 7, 2016 to August 3, 2019 by influenza season. A self-controlled case series analysis was performed using Conditional Poisson Regression to compare the risk of stroke in risk intervals (1-21 and 22-42 days) to a control interval (43-90 days). The exposures were high-dose or adjuvanted influenza vaccines. The stroke outcomes were non-hemorrhagic stroke (NHS), transient ischemic attack (TIA), NHS and/or TIA (NHS/TIA), and hemorrhagic stroke (HS).

Results: Among beneficiaries ≥65 years who received a high-dose/adjuvanted influenza vaccine, there were 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.
The age subgroup analyses showed significant associations for HS during the 22-42 day risk window in the 65-74 age subgroup in 2016-2017 (IRR=1.24, 95% CI 1.02−1.51; RD/100,000 doses=0.83, 95% CI 0.07−1.59), and in the 75-84 age subgroup in 2017-2018 (IRR=1.19, 95% CI 1.03−1.37; RD/100,000 doses=1.56, 95% CI 0.25−2.87). In 2018-2019, we identified significant associations in the 85+ age subgroup for NHS (IRR=1.17, 95% CI 1.06−1.29; RD/100,000 doses=6.40, 95% CI 2.34−10.47) and NHS/TIA (IRR=1.14, 95% CI 1.06−1.23; RD/100,000 doses=8.66, 95% CI 3.51−13.81) during the 1-21 day risk window.

Conclusions: Among adults aged ≥65 years who experienced stroke after vaccination, we did not observe clear, consistent evidence of increased stroke risk shortly following high-dose/adjuvanted influenza vaccination compared to a later time period across the three seasons. The statistically significant associations we identified were not consistently observed across outcomes, risk windows, age subgroups, or seasons. The clinical significance of any potential stroke risk following vaccination must be carefully considered together with the significant benefits of receiving an influenza vaccination.