Relative vaccine effectiveness of high-dose vs. standard-dose influenza vaccine against clinical outcomes according to history of atrial fibrillation: a pre-specified analysis of the DANFLU-1 randomized trial.

AIMS

Atrial fibrillation (AF) may be associated with adverse influenza-related outcomes. We assessed the relative vaccine effectiveness (rVE) of high-dose (HD-IIV) vs. standard-dose (SD-IIV) inactivated influenza vaccination against cardiovascular and all-cause hospitalizations and all-cause mortality according to history of AF.

METHODS AND RESULTS

This was a prespecified analysis of DANFLU-1, a pragmatic, open-label, feasibility trial randomizing adults aged 65-79 years 1:1 to HD-IIV or SD-IIV during the 2021-2022 influenza season in Denmark. Baseline and endpoint data were obtained from the nationwide administrative health registries. Prespecified endpoints included cardiovascular hospitalizations and all-cause mortality occurring 14 days after vaccination until 31 May 2022. Among 12 477 randomized participants, 878 (7.0%) had AF at baseline. Participants with AF were older (73.0 ± 3.8 vs. 71.7 ± 3.9 years, < 0.001), more likely to be male (70.7% vs. 51.5%, < 0.001) and have concomitant comorbidities. The incidence rate of hospitalization for AF was 75.5 vs. 5.1 per 1000 person-years for individuals with vs. without AF ( < 0.001). HD-IIV vs. SD-IIV was associated with a lower all-cause mortality rate irrespective of AF status (AF: 9 events, rVE 54.1%, 95% CI -114.7 to 92.6% vs. no AF: 53 events, rVE 48.3%, 95% CI 6.3-72.5%, pinteraction = 0.87). HD-IIV was not associated with a lower incidence of AF hospitalization regardless of AF status (overall rVE: 29.7%, 95% CI -13.9 to 57.1, pinteraction = 0.51).

CONCLUSION

Although DANFLU-1 was not powered for clinical endpoints, HD-IIV vs. SD-IIV was associated with lower all-cause mortality irrespective of AF status. HD-IIV compared with SD-IIV was not associated with a significantly lower incidence of AF hospitalizations regardless of AF status.