BACKGROUND: The high-dose inactivated influenza vaccine (HD-IIV) has demonstrated superior protection against a range of hospitalization end points versus standard-dose inactivated influenza vaccine (SD-IIV), but its effectiveness against specific cardiovascular outcomes and in those with pre-existing cardiovascular disease (CVD) is not well elucidated.
METHODS: In a prespecified secondary analysis of the FLUNITY-HD (Pooled Analysis of Methodologically Harmonized Pragmatic Randomized Trials of High-Dose vs. Standard-Dose Influenza Vaccine Against Severe Clinical Outcomes) individual-level pooled data set integrating 2 methodologically harmonized pragmatic, individually randomized trials conducted in Denmark and Spain, we investigated the relative vaccine effectiveness of HD-IIV versus SD-IIV against severe cardiovascular outcomes and according to pre-existing CVD among adults =65 years of age. Data were primarily obtained from routine health care databases, with follow-up from 14 days after vaccination to May 31 the following year.
RESULTS: The pooled data set encompassed 466 320 individually randomized participants, of whom 107 700 (23.1%) had a history of CVD. HD-IIV reduced the incidence of hospitalization for influenza or pneumonia, cardiorespiratory disease, laboratory-confirmed influenza, and any cause compared with SD-IIV, irrespective of the presence or absence of pre-existing CVD (Pinteraction>0.66 for all outcomes). Compared with the SD-IIV group, the HD-IIV group had a significantly lower incidence of hospitalization for any CVD (HD-IIV, 1.15%, versus SD-IIV, 1.24%; relative vaccine effectiveness, 6.6% [95% CI, 1.6-11.4]; P=0.010), hospitalization for any respiratory disease (HD-IIV, 0.92%, versus SD-IIV, 0.98%; relative vaccine effectiveness, 6.5% [95% CI, 0.7-11.9]; P=0.027), and hospitalization for heart failure (HD-IIV, 0.11%, versus SD-IIV, 0.15%; relative vaccine effectiveness, 21.3% [95% CI, 7.6-33.0]; P=0.003).
CONCLUSIONS: In a prespecified pooled analysis of 466 320 individually randomized older adults, HD-IIV reduced the incidence of a wide range of severe cardiovascular and respiratory outcomes compared with SD-IIV, with consistent findings regardless of previous history of CVD. Among cardiovascular outcomes, the protective effect of HD-IIV versus SD-IIV was particularly pronounced against hospitalization for heart failure.
REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT06506812.
| Discipline Area | Score |
|---|---|
| Family Medicine (FM)/General Practice (GP) |  |
| General Internal Medicine-Primary Care(US) | |
| Cardiology | |
| Public Health | |
| Geriatrics |  |
The conclusions support the strategy that high-dose influenza vaccines should be preferred in any case.
This large pooled individual-level analysis of pragmatic randomized trials provides robust evidence that high-dose influenza vaccination reduces cardiorespiratory and cardiovascular hospitalizations in older adults, with a more pronounced effect on heart failure admissions. However, absolute risk reductions are modest, and the study was not primarily powered for specific cardiovascular endpoints. Nonetheless, the results are clinically relevant and support preferential use of high-dose influenza vaccines in older populations as part of cardiovascular risk reduction strategies.
