Risk of Ischemic Stroke after COVID-19 Bivalent Booster Vaccination in an Integrated Health System

PurposeWhat is the absolute occurrence of ischemic stroke and transient ischemic attack after a COVID-19 bivalent vaccination? MethodsWe conducted a retrospective cohort study of Kaiser Permanente Northwest (KPNW) patients 18 years and older who were vaccinated with either the Pfizer or Moderna formulation of the COVID-19 bivalent vaccine between September 1, 2022 and March 1st 2023. Patients were included in the study if they had KP membership at the time of vaccination and through the 21-day follow up period. We replicated the Vaccine Safety Datalink (VSD) rapid cycle analysis methodology and searched for possible cases of ischemic stroke or TIA in the 21 days following vaccination using ICD-10-CM diagnosis codes in both the primary position and any position. We waited 90 days from the end of the follow up (March 21, 2023) for complete non-KP data accrual before analyzing the data to account for the lag in processing outside hospital insurance claims. Two physicians adjudicated possible cases by reviewing the clinical notes in the electronic health record. The analyses were stratified by age [≥]65 years to allow for comparisons with VSDs reporting at the Advisory Committee on Immunization Practices (ACIP) meeting of incidence of ischemic stroke or TIA (VSD reported incidence; 24.6 cases of ischemic stroke or TIA per 100,000 patients vaccinated). ResultsThe incidence of ischemic stroke or TIA was 34.3 per 100,000 (95% CI, 17.7 - 59.9) in patients 65 years or older who received the bivalent Pfizer vaccine--based on a diagnosis code in the primary position of the emergency department or hospital discharge. The incidence increased to 45.7 per 100,000 (95% CI 26.1 - 74.2) when we expanded the search to a diagnosis in any position and did not adjudicate to confirm. However, most of those additional apparent stroke or TIA diagnoses were false-positive diagnoses based on physicians adjudications. Estimating the incidence based on the primary position agreed closely with estimating the incidence based on any position and physician adjudication: 37.1 per 100,000 (95% CI 19.8 - 63.5). Seventy-nine percent of the ischemic stroke cases were admitted to hospitals that are not owned by the integrated delivery system. ConclusionWe identified a 50% increase in the incidence of ischemic stroke per 100,000 patients ages 65 and older vaccinated with the Pfizer bivalent vaccine, compared to the data presented by the VSD. Seventy-nine percent of the ischemic stroke cases were admitted to non-plan hospitals and a delay in processing outside hospital insurance claims was likely responsible for the discrepancy in case ascertainment of ischemic stroke. Physician adjudication of all cases in this study allowed accurate absolute incidence estimates of stroke per 100,000 vaccine recipients and is helpful in calculation of net benefit for policy recommendations and shared decision-making. 5 key pointsO_LIWe identified a 50% increase in incidence of ischemic stroke or transient ischemic attack (TIA) per 100,000 patients ages 65 and older vaccinated with the Pfizer bivalent vaccine, compared to the data presented by the Vaccine Safety Datalink (VSD). C_LIO_LISeventy-nine percent of the ischemic stroke and TIA cases were admitted to hospitals that are not owned by the integrated delivery system. C_LIO_LIA delay in processing outside hospital insurance claims was likely responsible for the discrepancy in case ascertainment of ischemic stroke. C_LIO_LIReplication of the VSD case definition confirmed the exceptionally high positive predictive value (PPV) in identifying ischemic stroke or TIA within 21 days of Pfizer bivalent vaccination in individuals 65 years and older when the ICD-10-CM hospital discharge code is restricted to the primary position. C_LIO_LIPhysician adjudication of all cases in this study allowed accurate absolute incidence estimates of stroke per 100,000 vaccine recipients and is helpful in calculation of net benefit for policy recommendations and shared decision-making. C_LI