Effect of bivalent RSV prefusion F protein-based vaccine on myocarditis and pericarditis: a prespecified safety analysis of the DAN-RSV trial

Background Myocarditis and pericarditis are inflammatory cardiac syndromes that have been monitored as outcomes of special interest in adult vaccination programs. Previous randomized and observational studies of RSVpreF vaccination have not identified an association with these events; however, given their low incidence, prior studies have not been sufficiently powered to exclude modest differences in risk. With more than 510,000 individually randomized participants across two seasons, DAN-RSV represents the largest study to date to assess the effect of RSVpreF vaccination on these rare inflammatory cardiac events. Purpose This prespecified analysis of the complete two-season cohort of the DAN-RSV trial will evaluate the effect of RSVpreF vaccination versus no vaccine on the risk of myocarditis and pericarditis. Methods DAN-RSV is a pragmatic, open-label, individually randomized trial conducted during the 2024/2025 and 2025/2026 winter seasons. In season one, individuals aged ≥60 years were randomized in Denmark. In season two, adults aged ≥18 years were randomized in Denmark and Galicia, Spain. In Denmark, recruitment was digital through the national electronic mail system, whereas in Galicia recruitment is conducted in person at primary and hospital-based outpatient settings. Participants are individually randomized 1:1 to receive RSVpreF vaccination or no RSV vaccination. Baseline characteristics and outcomes are obtained through linkage to regional and national health registries. Participants are followed for clinical outcomes starting 14 days after the booked study visit through May 31 of the corresponding vaccination season. Additional pre-specified analyses include comparisons of hospitalization rates for pericarditis (ICD-10 I30–I31) and myocarditis (ICD-10 I40–I41), defined as primary or secondary diagnoses during any hospital contact. Results In season one of the DAN-RSV trial, 131,276 participants were randomized to RSVpreF vaccination (n=65,642) or to the control group (n=65,634). The mean age was 69.4±6.5 years and 66,013 (50.3%) were male. In season two, 331,601 participants were randomized to RSVpreF vaccination (n=165,803) or to the control group (n=165,801) in Denmark. The mean age was 57.4±15.3 years and 145,562 (43.9%) were male. Additionally, >50,000 participants were recruited in Galicia, resulting in a total combined study population exceeding 510,000 individually randomized participants across the two seasons (Figure 1). Outcome data for myocarditis and pericarditis is not available at the time of abstract submission and will be presented at the ESC Congress. Conclusions DAN-RSV is the largest randomized RSVpreF vaccine trial to date to evaluate the effect of RSVpreF vaccination on risk of pericarditis and myocarditis.