The INVESTED trial was designed to investigate the antibody response elicited by high-dose trivalent versus standard-dose quadrivalent inactivated influenza vaccines and their relationship with clinical outcomes. In patients with heart failure or a history of myocardial infarction, the high-dose vaccine was found to induce a stronger humoral response. No association was observed between seroconversion status and the likelihood of hospitalization for cardiopulmonary issues or all-cause mortality. Vaccination against influenza remains essential, particularly in high-risk populations.
Antibody data were collected from 658 of the 5260 random participants (12.5%; average age 66.2 years; 507 males, 151 females; 348 with heart failure). The high-dose vaccine had increased antibody response to A/H1N1, A/H3N2, and B-type antigens compared with the standard dose. Over 92% of participants achieved seroprotection for each antigen, with higher seroconversion rates observed in those receiving the high-dose vaccine. However, seroconversion was not associated with a higher risk of cardiopulmonary hospitalization or all-cause mortality, irrespective of treatment group.
“The more pronounced antibody response observed in participants who received the high-dose vaccine confirmed expected patterns by randomization, with greater increases in mean titer and seroconversion rates for all antigens included in the high-dose vaccine formulation, together with the lower response for the B-lineage antigen contained only in the standard-dose quadrivalent vaccine,” according to the investigators. “Although high-dose vaccine elicited a more robust immune response, higher seroprotection levels and seroconversion status did not translate into benefits in all-cause mortality or cardiopulmonary hospitalizations in INVESTED, regardless of treatment group."
3 Key Takeaways
- The INVESTED trial found that in patients with heart failure or a history of myocardial infarction, the high-dose trivalent influenza vaccine elicited a stronger antibody response compared to standard-dose quadrivalent inactivated vaccine.
- Despite the more robust antibody response induced by the high-dose vaccine, the study did not find an association between the level of seroconversion and the likelihood of hospitalization for cardiopulmonary issues or all-cause mortality.
- Despite the lack of observed direct benefit in reducing cardiopulmonary hospitalizations or mortality linked to the antibody response, the INVESTED trial reinforces the importance of influenza vaccination in individuals with high-risk cardiovascular conditions.
This secondary analysis was a predetermined examination of the immune response within a subset of participants in the INVESTED trial, a randomized, double-blind, active-controlled study conducted across 157 locations in the US and Canada over 3 influenza seasons. Antibody levels were assessed using hemagglutination inhibition assays at randomization and again 4 weeks into the 2017-2018 and 2018-2019 seasons. Participants were eligible if they had been hospitalized for acute myocardial infarction or heart failure and had at least one additional risk factor. Data analysis was conducted from February 2023 to June 2023.
“Greater increases in mean titer and seroconversion rates for all antigens included in the high-dose vaccine formulation were observed, alongside the lower response for the B-lineage antigen contained only in the standard-dose quadrivalent vaccine,” according to investigators. “The magnitude of humoral response appears to be of limited predictive value for vaccine efficacy on adverse cardiopulmonary outcomes in patients at high cardiovascular risk, with seroprotection levels achieved with standard-dose compared with high-dose vaccine potentially having similar protective effects.”
Despite including over 10% of INVESTED's participants from various US and Canadian locations, the relatively small sample and varying initial participant characteristics might limit the broader applicability of the findings. While the even distribution of missing data across treatment groups minimized its impact, it could still have influenced the results. The analysis was limited to short-term antibody responses due to measurements taken only at baseline and after 4 weeks. The absence of a non-vaccinated control group in INVESTED means the study could not evaluate the overall efficacy of vaccination versus non-vaccination in preventing adverse clinical outcomes. Lastly, the study's results cannot be extended to other vaccine types.
These results highlight the need for further research to identify factors influencing vaccine effectiveness in reducing clinical events. The importance of influenza vaccination in high-risk groups is reaffirmed, emphasizing the need for continued evaluation of vaccine types and administration strategies to improve outcomes.
Reference
Peikert A, Claggett BL, Udell JA, et al. Influenza Vaccine Immune Response in Patients With High-Risk Cardiovascular Disease: A Secondary Analysis of the INVESTED Randomized Clinical Trial. JAMA Cardiol. Published April 7, 2024. Accessed April 8, 2024. doi:10.1001/jamacardio.2024.0468
