A large Danish trial analysis suggests high-dose flu vaccines may offer extra protection against serious influenza-related hospitalizations in seniors.
Study: High-Dose vs Standard-Dose Influenza Vaccine in Older Adults With Diabetes. Image credit: Andrew Angelov/Shutterstock.com
A study published in JAMA Internal Medicine suggests that high-dose influenza vaccine is associated with lower rates of selected influenza-related hospitalization outcomes than standard-dose vaccine in older adults with or without diabetes.
Diabetes heightens risk of influenza complications
Influenza, commonly known as flu, is an acute respiratory infection caused by influenza viruses. Approximately 1 billion influenza cases occur annually worldwide, including 3 to 5 million severe cases. Approximately 290,000 to 650,000 deaths occur each year due to severe infections.
Although the infection remains mild in most cases, children under 5 years of age, older adults, and those with comorbidities such as diabetes are at higher risk of developing severe respiratory and cardiovascular complications.
Seasonal influenza vaccines are primary preventive interventions against severe outcomes. However, the standard-dose inactivated influenza vaccine has been found to provide suboptimal protection, particularly in high-risk individuals.
Given the substantial burden of influenza, the high-dose inactivated influenza vaccine has been developed, containing 4-fold higher antigen levels than the standard vaccine. Currently, high-dose vaccination is preferred for adults aged 65 years or older in the US. However, only a few randomized trials have so far analyzed the protective efficacy of high-dose vaccination in susceptible older adults with diabetes.
In the current study, researchers conducted a prespecified secondary analysis of the DANFLU-2 randomized clinical trial in Denmark to compare the protective efficacy of high-dose and standard-dose influenza vaccines in older adults with or without diabetes.
Trial compares high-dose versus standard vaccination
The study included 332,438 older adults, including 43,881 with diabetes. Participants were randomly assigned to two groups, one receiving high-dose vaccination and the other receiving standard-dose vaccination.
Participants were followed up from 14 days after vaccination to May 31 of the following year. The efficacy of the two tested vaccines on prespecified cardiorespiratory, cardiovascular, and influenza-related hospitalization outcomes was analyzed in participants with or without diabetes.
High-dose vaccine linked to fewer influenza hospitalizations
The study analysis revealed that the high-dose influenza vaccine was associated with lower rates of hospitalization for several outcomes, most notably influenza-related hospitalizations, among older adults, with a consistent effect across diabetes status.
No overall differences were observed in hospitalization rates for any respiratory disease or myocardial infarction, suggesting that the benefits of high-dose vaccination were not uniform across all endpoints.
Among different diabetes subgroups, diabetes duration was found to modify the association between vaccine type and cardiorespiratory hospitalization. A lower incidence of cardiorespiratory hospitalizations was observed with high-dose vaccination among participants with diabetes of longer duration, but not among those with shorter duration.
Exploratory results highlight potential for targeted prevention
The study highlights a potential incremental benefit of high-dose influenza vaccine over standard-dose influenza vaccine in reducing hospitalizations for some, but not all, cardiorespiratory and cardiovascular outcomes, including influenza and laboratory-confirmed influenza, in older adults, irrespective of diabetes status.
These findings should be interpreted in the context of the DANFLU-2 trial’s neutral primary endpoint, hospitalization for influenza or pneumonia, and the authors emphasize that the secondary and subgroup analyses are exploratory.
Global public health authorities widely recommend annual influenza vaccination, particularly for individuals with chronic conditions, such as diabetes, due to their high vulnerability to complications, including cardiovascular complications.
The study finds a higher risk of hospitalization due to cardiorespiratory and cardiovascular complications in participants with diabetes than those without diabetes. These findings highlight the importance of optimizing preventive strategies for this high-risk population. Consistent with this higher baseline risk, the absolute benefit of high-dose vaccination was greater in individuals with diabetes, as reflected by lower numbers needed to vaccinate.
Moreover, the study reports a generally consistent direction of association between high-dose vaccination and reduced hospitalizations for cardiorespiratory disease, cardiovascular disease, and heart failure. However, several diabetes-specific estimates were imprecise and not statistically significant. Notably, no overall reduction in cardiovascular death was observed, reinforcing the need for cautious interpretation.
The observed influence of different diabetes characteristics, including diabetes duration, presence of diabetes-related complications, and glycated hemoglobin levels, a measure of glycemic control, on vaccine associations with hospitalization outcomes, suggests that the protective benefits of high-dose vaccination over standard-dose vaccination may be more prominent in individuals with more advanced diabetes, although these subgroup findings are hypothesis-generating.
The authors hypothesize that these findings may reflect a more pronounced suboptimal immune response to standard-dose vaccination in individuals with greater disease burden, as well as higher susceptibility to influenza-related complications associated with longer disease duration and a greater comorbidity burden.
Overall, the study findings highlight that high-dose influenza vaccination may offer superior benefits against selected severe outcomes in vulnerable populations through a single annual intervention that imposes no additional burden on the patients.
The DANFLU-2 trial data analyzed in this study were not specifically powered for subgroup analyses. These findings should therefore be considered as exploratory.
The trial did not have access to follow-up laboratory data, such as follow-up glycated hemoglobin levels, or to the Danish prescription registries, which limited the inclusion of data on filled prescriptions in baseline or endpoint definitions.
The study, therefore, could not determine the treatment patterns, including the use of glucose-independent cardiorenal protective and weight-lowering agents, such as glucagon-like peptide 1 receptor agonists and sodium-glucose cotransporter-2 inhibitors, and the balance between the groups.
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