Research Summary

Bivalent RSV Vaccine Lowers Cardiorespiratory Hospitalizations in Older Adults

Kate Young

Key Highlights

  • In a randomized trial of >130,000 adults aged ≥ 60 years, RSV prefusion F protein vaccination reduced all-cause cardiorespiratory hospitalizations by 9.9%.
  • No statistically significant differences were observed for isolated cardiovascular outcomes such as myocardial infarction, stroke, or heart failure.
  • Findings suggest potential downstream cardiovascular benefits of respiratory syncytial virus immunization in older adults.

A prespecified analysis of the DAN-RSV trial, published in JAMA, evaluated whether a bivalent respiratory syncytial virus prefusion F protein–based (RSVpreF) vaccine could prevent cardiovascular events in adults aged 60 years or older. The study, conducted in Denmark during the 2024–2025 winter season, builds on prior evidence linking respiratory syncytial virus (RSV) infection to increased cardiovascular morbidity and mortality.

The DAN-RSV trial enrolled 131,276 adults (mean age, 69.4 years; 50.3% male), randomly assigned 1:1 to RSVpreF vaccination or no vaccine. Of these, 28,662 participants (21.8%) had preexisting cardiovascular disease (CVD). Over a median follow-up of 22.4 weeks, cardiorespiratory hospitalizations occurred at rates of 26.3 vs 29.2 events per 1,000 participant-years in the RSVpreF and control groups, respectively — corresponding to a vaccine effectiveness of 9.9% (95% CI, 0.3%–18.7%; P = .04).

For cardiovascular-specific outcomes, hospitalization rates were 16.4 vs 17.7 events per 1,000 participant-years (vaccine effectiveness, 7.4%; 95% CI, –5.5% to 18.8%; P = .24). Stroke rates were 3.0 vs 3.8 events per 1,000 participant-years (vaccine effectiveness, 19.4%; P = .14). No significant differences were seen for myocardial infarction, heart failure, or atrial fibrillation. Results were consistent in as-treated analyses.

Subgroup analyses showed no interaction by baseline CVD status (P = .27), indicating similar effects in those with or without CVD. The authors noted that the reduced cardiorespiratory hospitalization rate likely reflected prevention of both respiratory and unrecognized cardiovascular events triggered by RSV infection.

Clinical Implications

While RSVpreF vaccination did not significantly reduce isolated cardiovascular hospitalizations, the overall reduction in cardiorespiratory admissions suggests a meaningful benefit in preventing severe complications among older adults. Given that RSV infection can trigger acute heart failure, ischemic events, and arrhythmias, even modest reductions in hospitalization rates may translate into substantial population-level benefits.

Based on a rate reduction of 2.9 events per 1,000 participant-years, approximately 345 individuals would need vaccination to prevent one hospitalization in a single RSV season. Extrapolated to the U.S. population, this could represent up to 575,000 fewer hospitalizations annually among older adults, according to estimates cited by the investigators.

The trial’s pragmatic design—leveraging Denmark’s national health registries and digital recruitment—demonstrated the feasibility of large-scale, real-world vaccine evaluation.

Expert Commentary

“The findings suggest potential downstream cardiorespiratory benefits of RSV immunization,” lead investigator Tor Biering-Sørensen, MD, MSc, MPH, PhD, and colleagues concluded. “The results support broader consideration of RSV vaccination in older adults, including among those with CVD, as part of a strategy to reduce severe cardiorespiratory complications.”

The DAN-RSV trial provides the largest randomized evidence to date suggesting that RSV vaccination may reduce overall cardiorespiratory morbidity in older adults. Although cardiovascular-specific outcomes require further study, these data support broader consideration of RSV immunization as part of preventive strategies for aging populations.

Reference
Lassen MCH, Johansen ND, Christensen SH, et al. Bivalent RSV prefusion f protein-based vaccine for preventing cardiovascular hospitalizations in older adults: a prespecified analysis of the DAN-RSV trial. JAMA. 2025;334(16):1431-1441. doi:10.1001/jama.2025.15405.