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Older Adults Benefit From High-Dose Influenza Vaccine


A high-dose influenza vaccine reduces the risk of death and incidence of hospitalization for influenza and pneumonia among older adults.

A high-dose influenza vaccine is associated with a reduction in the risk of death and in the incidence of hospitalization for influenza or pneumonia in older adults compared with standard-dose vaccinations, according to data presented at the European Society of Cardiology Congress 2022.

Risk of death was reduced by 49% and hospitalization incidence was reduced by 64% in the pragmatic randomized trial. Previous research found contracting influenza increased the risk of myocardial infarction by 6-fold in the week after and that 19% of heart failure hospitalizations could be attributed to influenza during the months with high influenza activity. Other research indicated vaccination against influenza prevents cardiovascular events.

“The reductions in hospitalizations and all-cause mortality with the high-dose vaccine were encouraging but require confirmation in a larger trial before potentially guiding clinical practice,” senior author and chief investigator Tor Biering-Sørensen, MD, PhD, MPH, of the Centre for Translational Cardiology and Pragmatic Randomised Trials at the University of Copenhagen in Denmark, said in a statement.

While most countries have approved high-dose influenza vaccines for adults 60 years and older, only a few countries offer this vaccine by default for older adults. As a result, high-dose vaccines are not widely used despite evidence that they provide additional protection compared with standard-dose vaccines, Biering-Sørensen said.

Standard-dose vaccines contain 15 μg of haemagglutinin antigen for each strain compared with high-dose vaccines which contain 60 μg.

The DANFLU-1 study integrated a pragmatic randomized trial into the official Danish vaccination program with a central trial site at a public university hospital and more than 1000 vaccination sessions across the country. It was an open-label study randomizing patients 1:1 to either high-dose or standard-dose quadrivalent influenza vaccine. While the primary objective was to evaluate the feasibility of the trial design, the secondary objective was to estimate the relative effectiveness of the high-dose vaccine.

Participants were between the ages of 65 and 79 years. Overall, 12,477 were included in the final analysis (6245 high-dose and 6232 standard-dose). The average age was 71.7 years and 47.1% were women.

Incidence of hospitalizations for influenza or pneumonia was lower for participants who received the high-dose vaccine compared with those who had the standard dose (10 vs 28 events, respectively). Individuals who received the high-dose vaccine also had a lower incidence of all-cause mortality (21 vs 41 events). Serious adverse events between the 2 groups were similar.

“Conducting an innovative pragmatic randomized trial in Denmark using administrative health registries as the primary data source was feasible,” Biering-Sørensen said. “Integrating an influenza vaccine trial into the official Danish vaccination program was also feasible. The next step is to conduct a fully powered trial of high-dose versus standard-dose quadrivalent influenza vaccine in older adults. The required sample size is expected to be around 200,000 participants.”

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