High-Dose vs Standard-Dose Influenza Vaccine and Cardiovascular Outcomes in Older Adults: A Prespecified Secondary Analysis of the DANFLU-2 Randomized Clinical Trial
Authors' conclusion
This study found reduced incidence of cardiorespiratory hospitalization among those who received HD-IIV vs SD-IIV, driven by a lower incidence of CV hospitalizations, and particularly heart failure hospitalizations.
Study context
- Population
- Adults aged ≥65 years regardless of comorbidity, Denmark, 2022/2023 to 2024/2025 influenza seasons91,026 (27.4%) with CVD history
- Participants
- 332,438 adults
- Comparison
- High-dose inactivated influenza vaccine (HD-IIV) vs SD-IIV
- HD-IIVn = 166,218
- SD-IIVn = 166,220reference
- Primary endpoint
- Severe cardiovascular (CV) outcomes:
- Prespecified secondary
- Exploratory end points of the trial
- Follow-up
- From 14 days after vaccination through May 31 the following year
Methodological detailsprespecified, pragmatic, open-label, individually randomised, nationwide registry-based, rerandomisation in additional seasons
- Prespecified
- Pragmatic
- Open-label
- Individually randomised
- Nationwide registry-based
- Rerandomisation in additional seasons
Primary result
As reported in the abstract
Hospitalization for any cardiorespiratory disease
Each group vs SD-IIVAbsolute difference, percentage points (95% CI)
HD-IIV
−0.13(−0.24 to −0.03)
- HD-IIV
- Relative vaccine effectiveness (rVE) 5.7% (95% CI 1.4%–9.9%)
Further findings
| Outcome | Absolute difference (percentage points) (95% CI) | |
|---|---|---|
| Hospitalization for any CVDHD-IIVvs SD-IIV | −0.10 (−0.18 to −0.02) | |
| Hospitalization for HFHD-IIVvs SD-IIV | −0.03 (−0.06 to −0.01) | |
| −0.2−0.100.1Difference, percentage points (linear scale) |
| Outcome | rVE (95% CI) |
|---|---|
| Hospitalization for any CVDHD-IIV vs SD-IIV | 7.5% (1.5%–12.5%) |
| Hospitalization for HFHD-IIV vs SD-IIV | 19.5% (3.3%–33.1%) |
Cardiorespiratory hospitalization, by history of CVD (subgroup)
- rVE did not differ by history of CVD vs no CVD at baseline
Trial primary end point: hospitalization for influenza or pneumonia
- HD-IIV did not significantly reduce hospitalization for influenza or pneumonia
Original publication
High-Dose vs Standard-Dose Influenza Vaccine and Cardiovascular Outcomes in Older Adults: A Prespecified Secondary Analysis of the DANFLU-2 Randomized Clinical Trial. JAMA Cardiol. Published 1 November 2025. doi:10.
Composed by AI from the published abstract and checked against it. How Briefs are made →