Influenza vaccination, incident atrial fibrillation, and cardiovascular outcomes

Influenza infection triggers cardiovascular events, and vaccination confers cardiovascular benefit in high-risk populations. Its role in preventing incident atrial fibrillation (AF) and cardiovascular outcomes in clinical practice remains uncertain. These associations were evaluated using a real-world target-trial emulation framework.

A retrospective cohort study was conducted using the TriNetX Global Collaborative Federated Research Data Network including adults with a routine healthcare visit in 2022. Influenza vaccination within the preceding year defined exposure; comparators had no recorded vaccination. A 1:1 propensity score matching across 65 baseline variables was applied. Outcomes included incident AF, cardiovascular events, and mortality, with subgroup analyses by age and baseline cardiovascular disease.

After matching, 276 888 patients (138 444 per group) were included with excellent covariate balance. During a mean follow-up of 2.7 ± 0.7 years, influenza vaccination was associated with a significantly lower risk of incident AF [hazard ratio (HR) 0.80, 95% confidence interval (CI) 0.76-0.84; P < .0001]. The absolute annualized incidence of AF was 0.9% in vaccinated patients vs 1.1% in non-vaccinated patients. Vaccinated patients also had lower risks of all-cause mortality (HR 0.85, 95% CI 0.82-0.89), myocardial infarction (HR 0.91, 95% CI 0.86-0.97), incident heart failure (HR 0.92, 95% CI 0.88-0.96), and cardiovascular-related hospitalization (HR 0.97, 95% CI 0.95-0.99). Associations were directionally consistent across age and cardiovascular disease subgroups, without significant effect modification.

In a large retrospective observational real-world cohort, influenza vaccination was associated with lower risks of incident AF and multiple cardiovascular outcomes. These findings support vaccination as a potential upstream strategy for AF prevention and highlight the need for randomized trials specifically designed to address AF-related outcomes.