JAMA Cardiol

High-dose flu vaccine linked to reduced heart inflammation

September 8, 2025

Study details: This prespecified secondary analysis of the DANFLU-2 randomized trial included 332,438 adults aged ≥65 years in Denmark, randomized to receive either high-dose (HD-IIV) or standard-dose (SD-IIV) inactivated influenza vaccines over three flu seasons. The study assessed CV outcomes using national health registries, regardless of participants’ baseline CV disease status.

Results: HD-IIV didn’t significantly reduce the primary endpoint of hospitalization for influenza or pneumonia. However, exploratory analyses showed HD-IIV was associated with a lower incidence of hospitalization for any cardiorespiratory disease (relative vaccine effectiveness [rVE], 5.7%; 95% confidence interval [CI], 1.4–9.9%), any CV disease (rVE, 7.5%; 95% CI, 1.5–12.5%), and heart failure (rVE, 19.5%; 95% CI, 3.3–33.1%) compared with SD-IIV. These effects were consistent regardless of baseline CV disease.

Clinical impact: While absolute differences were small, the findings suggest HD-IIV may offer meaningful cardiovascular protection in older adults. HD-IIV for patients ≥65 years could be considered, especially for those with or at risk for heart failure or myocarditis, as part of a broader strategy to reduce influenza-related cardiac complications.

Source:

Johansen ND, et al. (2025, August 30). JAMA Cardiol. High-Dose vs Standard-Dose Influenza Vaccine and Cardiovascular Outcomes in Older Adults: A Prespecified Secondary Analysis of the DANFLU-2 Randomized Clinical Trial. https://pubmed.ncbi.nlm.nih.gov/40884442/