Caroline Espersen, Mats C H Lassen, Niklas Dyrby Johansen, Slt Christensen, Negar Aliabadi, Kristoffer Grundtvig Skaarup, Daniel Modin, Kira Hyldekær Janstrup, Brian L. Claggett, Carsten Schade Larsen, Lykke Larsen, Lothar Wiese, Michael Dalager‐Pedersen, Matias G Lindholm, Anne Marie R Jensen, Maria Dons, Katrine F Bernholm, F Soeskov Davidovski, Lisa S Duus, C I Ottosen, Anne B Nielsen, Julie H. Borchsenius, Güldas Köse, Frederik H Fussing, Manan Pareek, Lars Køber, Scott D Solomon, Jens Ulrik Stæhr Jensen, Cyril Jean‐Marie Martel, Bradford D. Gessner, Claudia Schwarz, Elisa Gonzalez, Mette Skovdal, P Zhang, Elizabeth Begier, Tor Biering‐Sørensen
AIMS: Atrial fibrillation (AF) is a risk factor for respiratory syncytial virus (RSV)-related adverse cardiac events. This prespecified analysis of the DAN-RSV trial investigated RSVpreF vaccine effectiveness (VE) against respiratory and cardiovascular outcomes among older adults with and without AF. METHODS AND RESULTS: DAN-RSV was a pragmatic, open-label, individually randomized trial in Denmark during the 2024/2025 winter season. Adults ≥60 years were randomly assigned 1:1 to RSVpreF vaccine or no vaccine. Baseline and endpoint data were obtained from nationwide health registries. The primary endpoint was hospitalization for RSV-related respiratory tract disease, occurring 14 days after study visit until May 31, 2025. Prespecified respiratory and cardiovascular endpoints were assessed by AF status. Among 131,276 participants, 10,126 (7.7%) had a history of AF (mean age 73.2 ± 6.9 years, 30.4% female). AF participants had higher event rates compared with non-AF participants. RSVpreF vaccine lowered the incidence of the primary endpoint with no evidence of effect modification by AF status (AF: VE 80.6% (95%CI -84.7 to 99.6), no AF: VE 84.6% (95%CI 32.3 to 98.3), p-value for interaction >0.99). RSVpreF vaccine was further associated with a lower incidence of all-cause respiratory tract disease hospitalization (AF: VE 25.7% (95%CI -16.9 to 46.1), no AF: VE 13.0% (95%CI -3.3 to 27.8)) and RSV-related and overall cardio-respiratory disease hospitalization with no evidence of effect modification by AF status (p-value for interaction ≥0.45 for all). RSVpreF vaccine was not significantly associated with AF or stroke hospitalizations regardless of AF status (p-value for interaction≥0.34 for all). CONCLUSIONS: In older adults, RSVpreF vaccine was associated with a lower incidence of RSV-related and all-cause respiratory tract disease hospitalizations, as well as RSV-related and all-cause cardio-respiratory disease hospitalizations, with no evidence of effect modification by AF status.