Effect of High-Dose Trivalent vs standard-dose Quadrivalent Influenza Vaccine on Mortality or Cardiopulmonary Hospitalization in Patients with High-risk Cardiovascular Disease A Randomized Clinical Trial

Individuals with cardiovascular disease are more sensitive to influenza-related complications and adverse clinical outcomes. These individuals have a less vigorous immune response to standard-dose influenza vaccine. Orly Vardeny and colleagues have published a study in the JAMA network under the title “Effect of High-Dose Trivalent vs standard-dose Quadrivalent Influenza Vaccine on Mortality or Cardiopulmonary Hospitalization in Patients with High-risk Cardiovascular Disease A Randomized Clinical Trial”. The summary of the findings is below:

Objectives:

To investigate the effect of high-dose trivalent influenza vaccine vs with standard-dose quadrivalent influenza vaccine in reducing all-cause death or cardiopulmonary hospitalization in high-risk patients with cardiovascular disease.

Method:

In the study, 5260 participants were randomly assigned to receive high-dose trivalent or standard-dose quadrivalent inactivated influenza vaccine for up to 3 influenza seasons between September 21, 2016, and January 31, 2019. As per eligibility, patients with a recent acute myocardial infarction or heart failure hospitalization and at least one additional risk factor were included.
The primary outcome included the time required for all-cause death or cardiopulmonary hospitalization during every season. July 31, 2019, was the end date of follow-up. Vaccine-related adverse events were also examined.

Findings:

In comparison to standard-dose quadrivalent inactivated influenza vaccine, high-dose trivalent inactivated influenza vaccine failed to show a significant reduction in the composite of all-cause death or hospitalizations for cardiac or pulmonary causes. Additionally, there was no significant difference for any prespecified secondary endpoints between vaccine groups. This observation was consistent for all three seasons. Findings also suggest that participants receiving high dose vaccine had increased frequency of vaccine-induced adverse effects. On the other hand, there was no severe adverse effect on either of the group.
Evidence found that the incidence of hospitalization due to influenza was low in both groups; highlighting the importance of vaccination in this population.

Limitations:

As the trial focused on the therapeutic strategies on clinical outcomes, analysis of whether there is a specific reduction in influenza infection or illness remains unknown. The authors also acknowledge that some cases of hospitalization or death due to influenza might have got missed. This study lacked the unvaccinated control group, as current US guidelines strongly recommend influenza vaccination in high-risk populations. Authors acknowledge that findings can’t be generalized to all and need to be restricted in regions with different vaccination patterns. Lastly, the trial was discontinued early as it got far beyond the number of endpoints required.

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