High-Dose Flu Vaccine Cuts Myocarditis, Pericarditis Risk in Older Adults: Daily Dose

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On September 5, 2025, we reported on a study published in JAMA Network Open that was designed to examine the risk of myocarditis or pericarditis in older adults who received a high-dose inactivated influenza vaccine (HD-IIV) compared to those who received standard-dose IIVs (SD-IIVs).

The study

Researchers conducted a prespecified secondary analysis of the randomized DANFLU-2 clinical trial. The DANFLU-2 study was a pragmatic, registry-based, open-label randomized trial conducted in Denmark across the 2022–2023, 2023–2024, and 2024–2025 influenza seasons.

A total of 332 438 participants (mean age, 74 years; 51% men) were randomized 1:1 to HD-IIV or SD-IIV. Baseline characteristics were balanced across treatment groups, though participants with a history of myocarditis or pericarditis were older, more often men, and had higher rates of cardiovascular comorbidity.

Follow-up extended from day 14 post-vaccination through the end of each influenza season. The prespecified exploratory endpoint for this analysis was hospitalization for myocarditis or pericarditis identified by International Classification of Diseases, Tenth Revision (ICD-10) codes.

The findings

Over follow-up, 19 myocarditis or pericarditis events were recorded in the HD-IIV group versus 35 in the SD-IIV group, corresponding to a relative vaccine effectiveness (rVE) of 45.7% (95% CI, 2.5%-70.7%; P = .04). Results were consistent when including events that occurred within the first 14 days after vaccination. Rates of discontinuation and adverse events were low and similar between groups. Subgroup analysis showed that associations were consistent across baseline characteristics.

Authors' comments

"Despite sporadic reports of myocarditis and pericarditis associated with influenza vaccination,5 the consistency of our results with vs without inclusion of events occurring immediately after vaccination negates a dose-response association and a causal link."

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