Ischemic stroke after COVID-19 bivalent vaccine administration in patients aged 65 years and older: analysis of nation-wide patient electronic health records in the United States.

Importance: The Centers for Disease Control and Prevention (CDC) announced in January 2023 that they were investigating a potential connection between administration of the Pfizer novel coronavirus disease-2019 (COVID-19) bivalent vaccine booster and ischemic stroke (IS). Objective: To explore the relationship between Pfizer bivalent booster administration and IS in older patients in the United States and compare it to other COVID-19 vaccines. Design: A retrospective cohort study was conducted to compare hazard of IS among patients aged 65 years or over who received the Pfizer bivalent, Moderna bivalent, or Pfizer/Moderna monovalent COVID-19 booster vaccine 1-21 and 22-42 days after vaccination. Setting: Patient data were collected from TriNetX, a cloud-based analytics platform that includes electronic health record data from over 90 million unique patients in the United States. Participants: Patients in the United States aged 65 years or over at the time of administration of a Pfizer bivalent (n = 43,216), Moderna bivalent (n = 4,267), or Pfizer/Moderna monovalent (n = 100,583) booster were included for analysis. Cohorts were propensity-score matched by demographic factors and risk factors for IS and severe COVID-19. Exposures: Pfizer bivalent, Moderna bivalent, or Pfizer/Moderna monovalent COVID-19 booster administration. Main outcomes: The hazard ratio (HR) and 95% confidence interval (CI) for IS in the cohorts at 1-21 and 22-42 days after administration. Results: After matching, the Pfizer bivalent cohort included 4,267 patients, with an average age of 73.7 years (44.43% male, 76.59% white). The Moderna bivalent cohort included 4,267 patients, with an average age of 74.0 years (44.08% male, 77.39% white). There was no significant difference in the hazard of IS encounters between the Pfizer bivalent versus Moderna bivalent cohorts at 1-21- or 22-42-days post-administration: HR = 0.59 (0.31, 1.11), 0.73 (0.33, 1.60). The hazard for IS was lower in the Pfizer bivalent cohort than in the Pfizer/Moderna monovalent cohort at both timepoints: HR = 0.24 (0.19, 0.29), 0.25 (0.20, 0.31). Conclusions and relevance: Older adults administered the Pfizer bivalent booster had similar hazard for IS encounters compared to those administered the Moderna bivalent booster vaccine, but lower hazard than those administered the Pfizer/Moderna monovalent boosters.