• Among older adults, the incidence of myocarditis or pericarditis was lower among those who received the high-dose inactivated flu vaccine versus the standard-dose vaccine.
  • There were only two cases of myocarditis observed among over 300,000 study participants, both in the standard-dose group.
  • These results may not be generalizable to younger people, who are at greater risk of inflammatory cardiac conditions.

The high-dose inactivated influenza vaccine may deliver better protection against myocarditis and pericarditis compared with the standard-dose shot in older adults, according to a secondary analysis of the randomized DANFLU-2 trial.

Among over 300,000 participants ages 65 and older, the incidence of myocarditis or pericarditis was lower among those who received the high-dose vaccine versus the standard-dose vaccine (19 vs 35 events), with a relative vaccine effectiveness of 45.71% (95% CI 2.46-70.67, P=0.04), reported Tor Biering-S�rensen, MD, PhD, of the University of Copenhagen in Denmark, and colleagues.

There were no myocarditis cases among those in the high-dose vaccine group compared with two cases in the standard-dose group, and there were 19 cases of pericarditis among the high-dose group versus 33 cases in the standard-dose group, the authors noted in a research letter in JAMA Network Open opens in a new tab or window .

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

The open-label DANFLU-2 trial included 332,438 people ages 65 and older in Denmark during the 2022-2023, 2023-2024, and 2024-2025 flu seasons. Average age was 72.3 years, and 51.4% were men. Participants were randomized to either a quadrivalent high-dose inactivated flu vaccine (60 mcg of hemagglutinin antigen per strain) or a quadrivalent standard-dose inactivated flu vaccine (15 mcg).

During each study season, participants were followed up from day 14 after vaccination through May 31 the following year. Events occurring before 14 days after vaccination were included in a sensitivity analysis.

Among participants, 68.3% had a history of myocarditis or pericarditis prior to vaccination. Those people were more likely than those without such a history to be older (average age 74.2 vs 73.7), to be men (68.3% vs 51.3%), and to have a greater prevalence of comorbidities such as chronic cardiovascular disease (72.6% vs 27.2%), atrial fibrillation (41.3% vs 10.1%), or hypertension (37.9% vs 19.2%).

Among those without a history of myocarditis or pericarditis, 17 of those taking the high-dose vaccine subsequently developed either condition, compared with 31 of those receiving the standard-dose flu shot, for a relative vaccine effectiveness of 45.17% (95% CI -2.19 to 71.53). The relative vaccine effectiveness against pericarditis alone in this group was similar, at 41.38%, with 17 high-dose participants and 29 standard-dose participants developing pericarditis.

Limitations included the small number of myocarditis and pericarditis cases, with the implications for myocarditis particularly uncertain, given that there were only two cases. Implications were also unclear for younger adults, who are at greater risk of inflammatory cardiac conditions. In addition, DANFLU-2 did not compare vaccination with no vaccination.