Relative Effectiveness of High-Dose Versus Standard-Dose Influenza Vaccination Against Hospitalizations and Deaths According to Frailty Score: A Post Hoc Analysis of the DANFLU-1 Randomized Trial.
Espersen C., Johansen ND., Modin D., Janstrup KH., Nealon J., Samson S., Loiacono MM., Harris RC., Andrew MK., Larsen CS., Jensen AMR., Landler NE., Claggett BL., Solomon SD., Landray MJ., Gislason GH., Køber L., Jensen JUS., Sivapalan P., Biering-Sørensen T.
BACKGROUND: Frailty is a risk factor for adverse influenza-related outcomes. We assessed the effectiveness of high-dose inactivated influenza vaccination (HD-IIV) versus standard-dose inactivated influenza vaccination (SD-IIV) according to a frailty score. METHODS: This was a post hoc analysis of the randomized feasibility trial of HD-IIV versus SD-IIV conducted during the 2021-2022 influenza season in older adults aged 65-79 years. We assessed prespecified outcomes, including hospitalizations and deaths, as first and recurrent events. Frailty was defined according to the hospital frailty risk score (HFRS). RESULTS: Among 12 477 included participants (mean age, 71.7 years; 47.1% female), 10 689 (85.7%) were categorized as having low frailty (HFRS <5) and 1784 (14.3%) had intermediate or high frailty (HFRS ≥5). HD-IIV versus SD-IIV was associated with a lower risk of first and recurrent hospitalizations for pneumonia or influenza regardless of the HFRS. For participants with low frailty there were 22 events (hazard ratio [HR], 0.37 [95% confidence interval, .15-.96]) and 25 recurrent events (incidence rate ratio, 0.31 [.11-.84]), and for those with intermediate or high frailty there were 16 events (HR, 0.33 [.11-1.01]) and 18 recurrent events (incidence rate ratio, 0.28 [.09-.92]; P value for continuous interaction with HFRS [Pinteraction] = .92 for first and Pinteraction = .93 for recurrent events). The HFRS modified the association of HD-IIV versus SD-IIV with all-cause mortality (Pinteraction = .02), with an association with reduced risk in participants with low frailty only (43 events, HR, 0.26 [95% confidence interval, .13-.55]). CONCLUSIONS: HD-IIV was associated with a lower risk of first and recurrent hospitalizations for pneumonia and influenza compared with SD-IIV and may be preferred for older adults, irrespective of frailty status. The HFRS modified the association of HD-IIV versus SD-IIV with all-cause mortality.