In the DAN-RSV trial of 131,000 participants, RSVpreF lowered overall cardiorespiratory hospitalizations but showed no significant reduction in cardiovascular events.
A prespecified analysis of the DAN-RSV trial found that a bivalent respiratory syncytial virus prefusion F protein–based vaccine (RSVpreF) reduced all-cause cardiorespiratory hospitalizations in adults 60 years or older, although reductions in cardiovascular-specific outcomes were not statistically significant.1
The incidence of all-cause cardiorespiratory hospitalization was 26.3 per 1000 participant-years in the RSVpreF group compared with 29.2 per 1000 participant-years in controls, yielding a vaccine effectiveness of 9.9% (95% CI, 0.3%-18.7%; P = .04) and an absolute rate reduction of 2.90 events per 1000 participant-years (95% CI, 0.1-5.71). Subgroup analysis showed no significant interaction by baseline cardiovascular disease (CVD) status (vaccine effectiveness: 5% [95% CI, –11.2% to 16.7%] in participants with CVD, 15.2% [95% CI, 2.2%-27.1%] in those without; P = .27 for interaction).1
The randomized clinical trial, conducted in Denmark during the 2024-2025 winter season, included 131,276 adults (mean age, 69.4 years; 50.3% men), of whom 21.8% had preexisting CVD. For all-cause cardiovascular hospitalizations, incidence was 16.4 per 1000 participant-years with RSVpreF vs 17.7 per 1000 participant-years in controls (vaccine effectiveness, 7.4%; 95% CI, –5.5% to 18.8%; P = .24). Stroke incidence was numerically lower in the RSVpreF group (3 vs 3.8 per 1000 participant-years; vaccine effectiveness, 19.4%; 95% CI, –8.6% to 40.4%; P = .14), but this and other cardiovascular outcomes, including myocardial infarction, heart failure hospitalization, and atrial fibrillation, were not significantly different between groups.1
“The observed reduction in cardiorespiratory hospitalization appeared similar across cardiovascular subgroups, though the study was not powered for subgroup analyses,” investigators wrote. “These findings suggest possible downstream cardioprotective effects of RSV immunization that warrant further investigation.”1
Study limitations included the open-label design, limited power for cardiovascular-specific outcomes, reliance on registry data and routine RSV testing, possible misclassification of events, and restricted generalizability due to population homogeneity and potential healthy volunteer bias.1
In adults ≥60 years, RSVpreF vaccination reduced all-cause cardiorespiratory hospitalizations (26.3 vs 29.2 per 1000 PY; vaccine effectiveness, 9.9%; P=.04).
Cardiovascular-specific outcomes, including myocardial infarction, heart failure, atrial fibrillation, and stroke, were not significantly reduced.
Limitations include open-label design, limited statistical power for cardiovascular endpoints, and reliance on registry data and routine RSV testing.
Related Contagion coverage published on June 24, 2025, highlighted that “in adults over 60—and especially in the 60-74 age group—a substantial proportion of respiratory and cardiorespiratory hospitalizations…are attributable to RSV,” reinforcing Centers for Disease Control and Prevention guidance recommending vaccination for adults 75 years or older and for individuals at high risk aged 60 to 74 years. These findings emphasize that older adults face higher-than-recognized risks for serious RSV outcomes and underscore the importance of immunization in this population.2
Overall, investigators concluded that RSVpreF vaccination significantly reduced all-cause cardiorespiratory hospitalizations in older adults but not cardiovascular-specific hospitalizations, suggesting potential secondary benefits of RSV immunization on overall cardiorespiratory outcomes while leaving its role in cardiovascular prevention uncertain.1
