A prespecified secondary analysis of the DAN-RSV trial has found that a bivalent respiratory syncytial virus (RSV) vaccine is similarly effective against respiratory and cardiovascular outcomes in older adults, regardless of pre-existing atherosclerotic cardiovascular disease (ASCVD).¹
The bivalent RSV prefusion F protein-based (RSVpreF) vaccine contains stabilised prefusion F glycoproteins from RSV subgroups A and B. This analysis aimed to evaluate its effectiveness in individuals with and without ASCVD, a group known to be at higher risk for complications from RSV infection.
The DAN-RSV trial was a large, pragmatic, open-label, individually randomised trial conducted in Denmark during the 2024/2025 winter season. The study enrolled 131,276 adults aged 60 years or older, who were randomised on a 1:1 basis to receive either a single intramuscular injection of the RSVpreF vaccine or no vaccine.¹˒²
Baseline characteristics and outcomes were collected via nationwide health registries. The primary outcome was hospitalisation for RSV-related respiratory tract disease. The principal major adverse cardiovascular event (MACE) outcome was a composite of hospitalisation for myocardial infarction, stroke, or heart failure. This analysis specifically assessed for heterogeneity in vaccine effectiveness (VE) between participants with pre-existing ASCVD (n=14,241) and those without (n=117,035).
Participants with pre-existing ASCVD had a higher incidence rate for nearly all respiratory and cardiovascular outcomes compared to those without. For the primary outcome, VE was 80.0% (95% CI, 29.3–96.3) in participants without ASCVD and 100.0% (95% CI, −141.3 to 100.0) in those with ASCVD, showing consistent effectiveness across groups (P-interaction >0.99).¹
For the MACE outcome, VE was 9.3% (95% CI, −15.1 to 28.6) in the non-ASCVD group and 12.0% (95% CI, −34.6 to 43.3) in the ASCVD group (P-interaction=0.90). A significant interaction was observed for the outcome of stroke, where the vaccine appeared more effective in the ASCVD group (VE: 65.3%; 95% CI, 23.9–85.8) compared to the non-ASCVD group (VE: 3.9%; 95% CI, −34.0 to 31.1) (P-interaction=0.02).
The findings suggest that the RSVpreF vaccine’s relative effectiveness is consistent in older adults, whether or not they have pre-existing ASCVD. However, given the higher baseline risk of adverse events in the ASCVD population, this high-risk group may derive greater absolute benefits from vaccination. The authors noted that the significant reduction in stroke among ASCVD patients could be a chance finding due to the number of statistical tests performed.
Additional follow-up of the DAN-RSV cohort is planned, which may provide further clarity on the long-term cardiovascular benefits of RSV vaccination.
This study was funded by Pfizer Inc.
References
1. Pareek M, Lassen MCH, Johansen ND, et al. Effectiveness of bivalent respiratory syncytial virus prefusion F protein-based vaccine in individuals with or without atherosclerotic cardiovascular disease: the DAN-RSV trial. Eur Heart J 2025;46(41):4291–4298. https://doi.org/10.1093/eurheartj/ehaf679
2. Lassen MCH, Johansen ND, Christensen SH, et al. RSV prefusion F vaccine for preventing hospitalizations in older adults. N Engl J Med 2025. https://doi.org/10.1056/NEJMoa2509810
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