Research Summary

RSVpreF Reduces RSV Hospitalization Across Heart Failure Status

Anthony Calabro, MA

Key Highlights

  • The randomized trial included 511,535 participants, of whom 9351 had heart failure at baseline.
  • RSVpreF demonstrated 70.3% effectiveness against hospitalization for RSV-related respiratory tract disease.
  • Vaccine effectiveness did not differ significantly according to heart failure status.
  • RSVpreF reduced all-cause lower respiratory tract disease and cardiorespiratory hospitalizations but not cardiovascular or heart failure hospitalizations individually.

The bivalent respiratory syncytial virus (RSV) prefusion F protein–based vaccine (RSVpreF) reduced RSV-related respiratory tract disease hospitalizations regardless of heart failure status in a prespecified analysis of the extended DAN-RSV trial published in the European Journal of Heart Failure. The vaccine also reduced all-cause lower respiratory tract disease and cardiorespiratory hospitalizations compared with no vaccination.

DAN-RSV was a pragmatic, open-label, individually randomized clinical trial conducted during the 2024-2025 and 2025-2026 winter seasons. Participants were randomly assigned 1:1 to receive RSVpreF or no vaccine. The first season included adults aged ≥60 years in Denmark; the second expanded eligibility to adults aged ≥18 years in Denmark and Galicia, Spain.

The prespecified analysis evaluated first-season vaccine effectiveness among participants with and without heart failure. Outcomes included hospitalizations for RSV-related respiratory tract disease, lower respiratory tract disease, all-cause respiratory disease, cardiorespiratory disease, cardiovascular disease, and heart failure. Heart failure was identified through a hospital contact coded for the condition within 10 years before randomization.

Study Findings

The intention-to-treat population included 511,535 participants, of whom 9351 (1.8%) had heart failure at baseline. Among participants with heart failure, 4711 received RSVpreF and 4640 received no vaccine. Their mean age was 71.6 years, 31.3% were female, and 90.0% were enrolled in Denmark.

RSVpreF reduced RSV-related respiratory tract disease hospitalization, with vaccine effectiveness of 70.3% (95% CI, 49.7%-83.2%). Effectiveness did not differ significantly by heart failure status (P for interaction=.60). The vaccine also reduced all-cause lower respiratory tract disease hospitalization by 8.1% (95% CI, 0.2%-15.4%) and cardiorespiratory hospitalization by 6.2% (95% CI, 1.2%-11.1%). No reduction was observed in all-cause respiratory hospitalization, and there were no appreciable differences between groups in cardiovascular or heart failure hospitalization.

Among participants with heart failure, results were generally consistent across subgroups defined by time since diagnosis, sex, age, trial season, and country. The number needed to vaccinate was numerically lower for most outcomes among participants with heart failure than among those without heart failure.

Clinical Implications

According to the study authors, the findings provide randomized evidence supporting RSVpreF vaccination as preventive therapy for RSV-related and all-cause cardiorespiratory events among patients with heart failure. The authors noted that the higher baseline risk among participants with heart failure corresponded to a lower number needed to vaccinate.

The analysis was not powered to detect interactions, and multiple subgroup tests increased the possibility of chance findings. Heart failure was identified using diagnostic codes without echocardiographic or biochemical characterization, RSV testing was not systematic, and incomplete adherence may have attenuated the vaccine-effectiveness estimates.

Expert Commentary

“RSVpreF reduced RSV-related RTD and all-cause cardio-respiratory hospitalization compared with no vaccine, irrespective of HF status,” the researchers concluded.

Reference
Skaarup KG, Lassen MCH, Yafasov M, et al. RSV vaccine for preventing respiratory and cardiovascular hospitalizations in heart failure: a prespecified analysis of the extended DAN-RSV trial. Eur J Heart Fail. Published online September 7, 2026. doi:10.1093/ejhf/xuag282