Sex-based differences in risk of ischaemic stroke or systemic embolism after BNT162b2 or CoronaVac COVID-19 vaccination in patients with atrial fibrillation: a self-controlled case series and nested case-control study

AIMS: Patients with atrial fibrillation (AF) have a higher risk of ischaemic stroke or systemic embolism, with a greater risk for female patients. This study aims to evaluate the risk of ischaemic stroke or systemic embolism and bleeding following COVID-19 vaccination in patients with AF and the sex differences. METHODS AND RESULTS: Self-controlled case series (SCCS) analysis was conducted to evaluate the risk of ischaemic stroke or systemic embolism and bleeding following BNT162b2 or CoronaVac in patients with AF, using the territory-wide electronic medical records from the Hospital Authority and vaccination records from the Department of Health in Hong Kong. Patients with a primary diagnosis of ischaemic stroke, systemic embolism, or bleeding in the inpatient setting between 23 February 2021 and 31 March 2022 were included. A nested case-control analysis was also conducted with each case randomly matched with 10 controls according to sex, age, Charlson comorbidity index, and date of hospital admission. Conditional Poisson regression was used in the SCCS analysis, and conditional logistic regression was used in the nested case-control analysis to assess the risks, and all analyses were stratified by sex and type of vaccines. Among 51 158 patients with AF, we identified an increased risk of ischaemic stroke or systemic embolism after the first dose of BNT162b2 in SCCS analysis during 0–13 days [incidence rate ratio 6.60, 95% confidence interval (CI) 1.51–28.77] and 14–27 days (6.53, 95% CI 1.31–32.51), and nested case-control analysis during 0–13 days (adjusted odds ratio 6.21, 95% CI 1.14–33.91) and 14–27 days (5.52, 95% CI 1.12–27.26) only in female patients. The increased risk in female patients following the first dose of CoronaVac was only detected during 0–13 days (3.88, 95% CI 1.67–9.03) in the nested case-control analysis. No increased risk of ischaemic stroke or systemic embolism was identified in male patients, and no increased risk of bleeding was detected in all patients with AF for both vaccines. An increased risk of ischaemic stroke or systemic embolism after COVID-19 was also observed in both females (17.42, 95% CI 5.08–59.73) and males (6.63, 95% CI 2.02–21.79). CONCLUSIONS: The risk of ischaemic stroke or systemic embolism after COVID-19 vaccination was only increased in female patients with AF. However, as the risk after COVID-19 was even higher, proactive uptake of COVID-19 vaccines is recommended to prevent the potential severe outcomes after infection.