tetano
Editor, Senior Moderator
Circulation
. 2025 Nov 10.
doi: 10.1161/CIRCULATIONAHA.125.077801. Online ahead of print. High-Dose vs. Standard-Dose Influenza Vaccine and Cardiovascular Outcomes in Older Adults: The FLUNITY-HD Prespecified Pooled Analysis
Niklas Dyrby Johansen[SUP] 1 [/SUP], Daniel Modin[SUP] 1 [/SUP], Jacobo Pardo-Seco[SUP] 2 [/SUP], Carmen Rodriguez-Tenreiro-Sánchez[SUP] 3 [/SUP], Matthew M Loiacono[SUP] 4 [/SUP], Rebecca C Harris[SUP] 5 [/SUP], Marine Dufournet[SUP] 6 [/SUP], Robertus van Aalst[SUP] 7 [/SUP], Ayman Chit[SUP] 8 [/SUP], Carsten Schade Larsen[SUP] 9 [/SUP], Lykke Larsen[SUP] 10 [/SUP], Lothar Wiese[SUP] 11 [/SUP], Michael Dalager-Pedersen[SUP] 12 [/SUP], Brian L Claggett[SUP] 13 [/SUP], Kira Hyldekær Janstrup[SUP] 1 [/SUP], Carmen Duran-Parrondo[SUP] 14 [/SUP], Marta Piñeiro-Sotelo[SUP] 14 [/SUP], Martín Cribeiro-González[SUP] 15 [/SUP], Mónica Conde-Pájaro[SUP] 14 [/SUP], Susana Mirás-Carballal[SUP] 14 [/SUP], Juan-Manuel González-Pérez[SUP] 16 [/SUP], Scott D Solomon[SUP] 13 [/SUP], Pradeesh Sivapalan[SUP] 17 [/SUP], Cyril Jean-Marie Martel[SUP] 18 [/SUP], Jens Ulrik Stæhr Jensen[SUP] 17 [/SUP], Federico Martinón-Torres[SUP] 3 [/SUP], Tor Biering-Sørensen[SUP] 19 [/SUP]; DANFLU-2 Study Group and the GALFLU Trial Team
Affiliations
Background: The high-dose inactivated influenza vaccine (HD-IIV) has demonstrated superior protection against a range of hospitalization endpoints versus standard-dose inactivated influenza vaccine (SD-IIV), but its effectiveness against specific cardiovascular (CV) outcomes and in those with pre-existing CV disease (CVD) is not well elucidated.
Methods: In a prespecified secondary analysis of the FLUNITY-HD individual-level pooled dataset integrating two methodologically harmonized pragmatic, individually randomized trials conducted in Denmark and Spain, we investigated the relative vaccine effectiveness (rVE) of HD-IIV vs. SD-IIV against severe CV outcomes and according to pre-existing CVD among adults aged ≥65 years. Data were primarily obtained from routine healthcare databases, with follow-up from 14 days post-vaccination to May 31 the following year.
Results: The pooled dataset 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, cardio-respiratory disease, laboratory-confirmed influenza, and any cause compared with SD-IIV, irrespective of the presence or absence of pre-existing CVD (p[SUB]interaction[/SUB]> 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% vs. SD-IIV, 1.24%; rVE, 6.6%; 95% CI, 1.6 to 11.4; P=0.010), hospitalization for any respiratory disease (HD-IIV, 0.92% vs. SD-IIV, 0.98%; rVE, 6.5%; 95% CI, 0.7 to 11.9; P=0.027), and hospitalization for heart failure (HD-IIV, 0.11% vs. SD-IIV, 0.15%; rVE, 21.3%; 95% CI, 7.6 to 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 CV and respiratory outcomes compared with SD-IIV, with consistent findings regardless of prior history of CVD. Among CV outcomes, the protective effect of HD-IIV vs. SD-IIV was particularly pronounced against hospitalization for heart failure.
. 2025 Nov 10.
doi: 10.1161/CIRCULATIONAHA.125.077801. Online ahead of print. High-Dose vs. Standard-Dose Influenza Vaccine and Cardiovascular Outcomes in Older Adults: The FLUNITY-HD Prespecified Pooled Analysis
Niklas Dyrby Johansen[SUP] 1 [/SUP], Daniel Modin[SUP] 1 [/SUP], Jacobo Pardo-Seco[SUP] 2 [/SUP], Carmen Rodriguez-Tenreiro-Sánchez[SUP] 3 [/SUP], Matthew M Loiacono[SUP] 4 [/SUP], Rebecca C Harris[SUP] 5 [/SUP], Marine Dufournet[SUP] 6 [/SUP], Robertus van Aalst[SUP] 7 [/SUP], Ayman Chit[SUP] 8 [/SUP], Carsten Schade Larsen[SUP] 9 [/SUP], Lykke Larsen[SUP] 10 [/SUP], Lothar Wiese[SUP] 11 [/SUP], Michael Dalager-Pedersen[SUP] 12 [/SUP], Brian L Claggett[SUP] 13 [/SUP], Kira Hyldekær Janstrup[SUP] 1 [/SUP], Carmen Duran-Parrondo[SUP] 14 [/SUP], Marta Piñeiro-Sotelo[SUP] 14 [/SUP], Martín Cribeiro-González[SUP] 15 [/SUP], Mónica Conde-Pájaro[SUP] 14 [/SUP], Susana Mirás-Carballal[SUP] 14 [/SUP], Juan-Manuel González-Pérez[SUP] 16 [/SUP], Scott D Solomon[SUP] 13 [/SUP], Pradeesh Sivapalan[SUP] 17 [/SUP], Cyril Jean-Marie Martel[SUP] 18 [/SUP], Jens Ulrik Stæhr Jensen[SUP] 17 [/SUP], Federico Martinón-Torres[SUP] 3 [/SUP], Tor Biering-Sørensen[SUP] 19 [/SUP]; DANFLU-2 Study Group and the GALFLU Trial Team
Affiliations
- PMID: 41212981
- DOI: 10.1161/CIRCULATIONAHA.125.077801
Background: The high-dose inactivated influenza vaccine (HD-IIV) has demonstrated superior protection against a range of hospitalization endpoints versus standard-dose inactivated influenza vaccine (SD-IIV), but its effectiveness against specific cardiovascular (CV) outcomes and in those with pre-existing CV disease (CVD) is not well elucidated.
Methods: In a prespecified secondary analysis of the FLUNITY-HD individual-level pooled dataset integrating two methodologically harmonized pragmatic, individually randomized trials conducted in Denmark and Spain, we investigated the relative vaccine effectiveness (rVE) of HD-IIV vs. SD-IIV against severe CV outcomes and according to pre-existing CVD among adults aged ≥65 years. Data were primarily obtained from routine healthcare databases, with follow-up from 14 days post-vaccination to May 31 the following year.
Results: The pooled dataset 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, cardio-respiratory disease, laboratory-confirmed influenza, and any cause compared with SD-IIV, irrespective of the presence or absence of pre-existing CVD (p[SUB]interaction[/SUB]> 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% vs. SD-IIV, 1.24%; rVE, 6.6%; 95% CI, 1.6 to 11.4; P=0.010), hospitalization for any respiratory disease (HD-IIV, 0.92% vs. SD-IIV, 0.98%; rVE, 6.5%; 95% CI, 0.7 to 11.9; P=0.027), and hospitalization for heart failure (HD-IIV, 0.11% vs. SD-IIV, 0.15%; rVE, 21.3%; 95% CI, 7.6 to 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 CV and respiratory outcomes compared with SD-IIV, with consistent findings regardless of prior history of CVD. Among CV outcomes, the protective effect of HD-IIV vs. SD-IIV was particularly pronounced against hospitalization for heart failure.