Key result
High-dose influenza vaccine cuts influenza or pneumonia hospitalizations ~9% vs standard dose.
Why the study?
Does high-dose inactivated influenza vaccine (HD-IIV) reduce hospitalization for influenza or pneumonia compared with standard-dose inactivated influenza vaccine (SD-IIV) in older adults aged ≥65 years according to baseline atrial fibrillation status?
RCT (n=466,320)
Individually randomized
Yes
Does high-dose inactivated influenza vaccine (HD-IIV) reduce hospitalization for influenza or pneumonia compared with standard-dose inactivated influenza vaccine (SD-IIV) in older adults aged ≥65 years according to baseline atrial fibrillation status?
High-dose inactivated influenza vaccine provides consistent relative protection against hospitalizations compared to standard-dose vaccine in older adults regardless of atrial fibrillation status, while conferring a larger absolute risk reduction and lower number needed to vaccinate among those with atrial fibrillation.
Background The FLUNITY-HD study, a prespecified pooled analysis including 466,320 individually randomized older adults, showed that high-dose inactivated influenza vaccine (HD-IIV) provided superior protection against hospitalization outcomes compared with standard-dose inactivated influenza vaccine (SD-IIV) among individuals aged ≥65 years. However, it has not been previously explored in this study whether the relative vaccine effectiveness of HD-IIV versus SD-IIV varies according to the presence of atrial fibrillation (AF). Methods We performed a prespecified analysis within FLUNITY-HD to assess relative vaccine effectiveness (rVE) according to AF status using data from two methodologically harmonized, individually randomized trials conducted in Denmark and Spain. Outcomes were ascertained using routinely collected healthcare data, with follow-up from 14 days after vaccination until May 31 of the subsequent year. Primary and secondary outcomes assessed the rVE of HD-IIV vs SD-IIV against various respiratory, all-cause hospitalization and mortality endpoints , and in this prespecified analysis treatment effect by baseline AF status and duration of AF was evaluated. Results A total of 466,320 individually randomized participants were included in the analysis (233,311 HD-IIV; 233,009 SD-IIV), 38,222 (8.2 %) had AF at baseline. Mean age was 73.3 years (SD 5.4) overall and 75.9 years (SD 6.0) in the AF sub-group. The primary endpoint of hospitalization for influenza or pneumonia occurred in 554 (1.4%) AF vs. 2,195 (0.5%) non-AF participants. HD-IIV provided superior protection (overall rVE 8.8%; 95%CI (1.7 to 15.5), P-value = 0.0082) compared with SD-IIV against the primary endpoint, with consistent rVE regardless of baseline AF status (P interaction = 0.92), Figure 1. Overall, HD-IIV vaccination reduced the incidence of cardiorespiratory hospitalization, laboratory confirmed influenza hospitalization, hospitalization for influenza any cardiovascular hospitalization and hospitalization for heart failure compared to SD-IIV, with no effect modification by baseline AF status (all P interaction > 0.10). Number Needed to Vaccinate (NNV) was lower among AF participants for all hospitalization related outcomes, as low as 246 needed to switch from SD-IIV to HD-IIV to avert one cardiorespiratory hospitalization in AF patients. AF duration significantly modified the effect of HD-IIV versus SD-IIV for cardiorespiratory and all-cause hospitalization (P interaction = 0.03 and 0.04), with no significant interaction for other primary and secondary outcomes (all P interaction > 0.17), Figure 2. Conclusion Vaccination with HD-IIV was associated with greater protection against hospitalization than SD-IIV, and this benefit was consistent irrespective of AF status. Notably, patients with AF derived a larger absolute risk reduction and a lower NNV, underscoring the clinical and public health importance of HD-IIV in this high-risk population.Main outcomesAF duration
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Hosseini et al. (2026) conducted an RCT in Atrial fibrillation in older adults receiving influenza vaccination (n=466,320). High-dose inactivated influenza vaccine (HD-IIV) vs. Standard-dose inactivated influenza vaccine (SD-IIV) was evaluated on Hospitalization for influenza or pneumonia (rVE 8.8%, 95% CI 1.7-15.5, p=0.0082). High-dose vs standard-dose influenza vaccine provided superior protection against influenza or pneumonia hospitalization (rVE 8.8%, 95% CI 1.7-15.5; P=0.0082), regardless of AF status (P-int=0.92).
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