High-Dose Versus Standard-Dose Influenza Vaccine and Cardiovascular Outcomes in Older Adults: The FLUNITY-HD Prespecified Pooled Analysis.

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 (>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]; =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]; =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]; =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.