Background: Bivalent COVID-19 mRNA booster vaccinations first became available in France in October 2022. In January 2022, a CDC vaccine database uncovered a possible safety issue in which people 65 and older were more likely to have an ischemic stroke 21 days after receiving the Pfizer/BioNTech bivalent shot, compared with days 22-44. Our two previous nationwide studies detected no increase in cardiovascular events following the Pfizer-BioNTech original vaccine.
Objectives: We aimed to assess whether the risk of acute myocardial infarction, hemorrhagic stroke, ischemic stroke, or pulmonary embolism differs after receiving the Pfizer-BioNTech COVID-19 mRNA bivalent booster dose compared to the Pfizer-BioNTech original vaccine.
Methods: This population-based study used the French National Health Data System linked to the national COVID-19 vaccination database. Eligible participants were all persons aged 50 years or more receiving a booster shot with either the bivalent or the original Pfizer-BioNTech vaccine between the 6th of October and the 9th of November 2022 (period during which the two vaccines were administered concomitantly). Each day during this period, individuals receiving the original vaccine were matched to up to five receiving the bivalent one (Matching Ratios: 13.8 % 1: 1, 20.2 % 1: 2, and 66.0 % 1: 5). End of follow-up was 21 days post-vaccination. The primary endpoints were cardiovascular events in a time-to-event analysis using propensity score-weighted Cox proportional hazards regression models, estimating weighted hazard ratios (wHRs) and 95% CIs.
Results: A total of 470 962 participants were included (mean [SD] age, 72.6 [10.4] years), with 97 234 (20.6%) receiving Pfizer-BioNTech original matched to 373 728 (79.4%) receiving Pfizer-BioNTech bivalent. The total number of cardiovascular events was 439. The most frequent events were myocardial infarction (151 patients [34.4%]) and ischemic stroke (148 patients [33.7%]). No increased risk associated with the Pfizer-BioNTech bivalent was found for any outcome: Ischemic stroke (wHR, 0.9; 95% CI, 0.6 - 1.3); Hemorrhagic stroke (wHR, 0.9; 95% CI, 0.5 - 1.6); Myocardial infarction (wHR, 0.9; 95% CI, 0.6 - 1.4); Pulmonary embolism (wHR, 0.8; 95% CI, 0.5 - 1.4); All four events combined (wHR, 0.9; 95% CI, 0.7 - 1.1).
Conclusions: We found no evidence of an increased risk of cardiovascular events after the Pfizer-BioNTech COVID-19 mRNA bivalent vaccine compared to the original vaccine in the 21 days following the booster dose. Our results are thus reassuring regarding the cardiovascular and ischemic stroke risks following the receipt of the Pfizer/BioNTech bivalent vaccine.
