Influenza infection increases the risk of cardiovascular complications – including myocardial infarction, heart failure exacerbations, and arrhythmias.
Growing evidence suggests that influenza vaccination helps lower this risk, particularly in individuals with pre-existing cardiovascular disease (CVD).
One of the key supporting studies was “Influenza Vaccination After Myocardial Infarction” (2021), which demonstrated that, compared to placebo, the standard influenza vaccine reduced the risk of death, recurrent myocardial infarction, or stent thrombosis by 28% among patients recently hospitalized for myocardial infarction or who have coronary artery disease.
These findings have since been integrated into clinical guidelines, and influenza vaccination is now officially recommended for patients with acute coronary syndrome.
However, standard vaccines do not always provide sufficient protection, particularly in older adults and those with CVD. To enhance vaccine efficacy, a high-dose formulation was developed, providing approximately 25% greater protection against laboratory-confirmed influenza compared to the standard dose.
Nevertheless, in the large INVESTED trial involving more than 5,000 patients recently hospitalized for myocardial infarction or heart failure, the high-dose vaccine did not significantly reduce the risk of death or rehospitalization compared to the standard vaccine.
To obtain more comprehensive data, Danish researchers conducted a secondary analysis of DANFLU-2, evaluating the effectiveness of the high-dose quadrivalent influenza vaccine compared to the standard vaccine among a broader population of adults aged 65 and older.
Participants and Intervention
The study enrolled over 332,400 participants, randomly assigned to two groups:
- HD-IIV (166,218 participants) – received a single dose of the high-dose quadrivalent influenza vaccine (Fluzone High-Dose Quadrivalent or Efluelda);
- SD-IIV (166,220 participants) – received a single dose of the standard quadrivalent influenza vaccine (VaxigripTetra, Sanofi).
Each strain in the HD-IIV contained 60 µg of hemagglutinin antigen, which is four times higher than the 15 µg per strain found in the SD-IIV.
Cardiovascular disease history was present in 27.4% of participants, including:
- 4% with coronary artery disease,
- 8% with prior myocardial infarction,
- 1% with heart failure,
- 3% with atrial fibrillation.
Participants with a CVD history tended to be older and more likely to have non-cardiovascular comorbidities, such as cancer or chronic lung disease.
High-Dose Vaccine Reduces Hospitalizations for Cardiovascular Diseases
In the DANFLU-2 study, the rate of hospitalizations due to any cardiorespiratory disease was 2.25% among those receiving the high-dose influenza vaccine and 2.38% among those given the standard vaccine.
Hospitalizations for any cardiovascular cause occurred in 1.30% of HD-IIV recipients and 1.40% of SD-IIV recipients – corresponding to a 7.2% reduction in hospitalization risk with the high-dose vaccine.
For respiratory diseases, the difference was minor (1.01% vs. 1.05%, respectively).
Among different cardiovascular outcomes, the most significant effect was observed in heart failure, where the risk of hospitalization was 19.5% lower with the high-dose vaccine compared to the standard vaccine.
The absolute risk difference for cardiorespiratory hospitalizations was approximately 0.13%, meaning that 732 people would need to receive the high-dose vaccine instead of the standard one to prevent one additional cardiorespiratory event.
Conclusion
Hospitalization rates for cardiorespiratory diseases were lower among those who received the high-dose influenza vaccine compared to the standard-dose vaccine.
The reduction was particularly striking for heart failure hospitalizations – nearly 20% lower than with the standard vaccine.
The differences between groups became more pronounced during periods of high influenza activity, indicating that the benefit is closely linked to infection prevention.
Therefore, high-dose influenza vaccination in older adults may provide additional protection against cardiovascular complications during flu seasons.
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