TY - JOUR
T1 - Bivalent RSV Prefusion F Protein-Based Vaccine for Preventing Cardiovascular Hospitalizations in Older Adults
T2 - A Prespecified Analysis of the DAN-RSV Trial
AU - Lassen, Mats C Højbjerg
AU - Johansen, Niklas Dyrby
AU - Christensen, Sine H
AU - Aliabadi, Negar
AU - Skaarup, Kristoffer G
AU - Modin, Daniel
AU - Claggett, Brian L
AU - Larsen, Carsten S
AU - Larsen, Lykke
AU - Wiese, Lothar
AU - Dalager-Pedersen, Michael
AU - Lindholm, Matias G
AU - Jensen, Anne Marie R
AU - Dons, Maria
AU - Bernholm, Katrine F
AU - Davidovski, Filip S
AU - Duus, Lisa S
AU - Ottosen, Camilla I
AU - Nielsen, Anne B
AU - Borchsenius, Julie H
AU - Espersen, Caroline
AU - Köse, Güldas
AU - Fussing, Frederik H
AU - Pareek, Manan
AU - Køber, Lars
AU - Solomon, Scott D
AU - Jensen, Jens Ulrik Stæhr
AU - Martel, Cyril Jean-Marie
AU - Gessner, Bradford D
AU - Schwarz, Claudia
AU - Gonzalez, Elisa
AU - Skovdal, Mette
AU - Moulton, Lawrence H
AU - Zhang, Pingping
AU - Begier, Elizabeth
AU - Biering-Sørensen, Tor
PY - 2025/10/28
Y1 - 2025/10/28
N2 - IMPORTANCE: Respiratory syncytial virus (RSV) infection is linked to elevated cardiovascular risk, particularly in individuals with preexisting cardiovascular disease (CVD). A bivalent RSV prefusion F protein (RSVpreF) vaccine was recently approved for preventing RSV-related lower respiratory tract illness, but its effectiveness against cardiovascular outcomes has not been evaluated in a randomized trial.OBJECTIVE: To investigate the vaccine effectiveness of RSVpreF compared with no vaccine against cardiovascular outcomes among adults aged 60 years or older.DESIGN, SETTING, AND PARTICIPANTS: Prespecified secondary analysis of the DAN-RSV trial, a pragmatic, open-label, individually randomized clinical trial conducted in Denmark during the 2024-2025 winter season. The first participant was enrolled on November 18, 2024. Adults aged 60 years or older were eligible for inclusion regardless of comorbidity status.INTERVENTIONS: Participants were randomized 1:1 to receive RSVpreF (n = 65 642) or no vaccine (n = 65 634).MAIN OUTCOMES AND MEASURES: Hospitalization for any cardiorespiratory disease was a prespecified secondary outcome, and hospitalizations for any CVD, heart failure, myocardial infarction, stroke, and atrial fibrillation were prespecified exploratory outcomes. Outcomes were assessed from 14 days after booked study visit through May 31, 2025. Vaccine effectiveness was calculated as 1 - incidence rate ratio, expressed as a percentage.RESULTS: Of 131 276 participants included (mean age, 69.4 [SD, 6.5] years; 50.3% male), 28 662 (21.8%) had preexisting CVD. All-cause cardiorespiratory hospitalization incidence was lower in the RSVpreF group compared with the control group (26.3 vs 29.2 events per 1000 participant-years [PY]; absolute rate reduction, 2.90 [95% CI, 0.10-5.71] per 1000 PY; vaccine effectiveness, 9.9% [95% CI, 0.3%-18.7%]; P = .04). There was no significant interaction by baseline CVD status (CVD at baseline: vaccine effectiveness, 5.0% [95% CI, -11.2% to 16.7%]; no CVD at baseline: vaccine effectiveness, 15.2% [95% CI, 2.2%-27.1%]; P = .27 for interaction). For the RSVpreF group vs control group, respectively, incidence rates of all-cause cardiovascular hospitalization were 16.4 vs 17.7 events per 1000 PY (vaccine effectiveness, 7.4% [95% CI, -5.5% to 18.8%]; P = .24), and incidence rates of stroke were 3.0 vs 3.8 events per 1000 PY (vaccine effectiveness, 19.4% [95% CI, -8.6% to 40.4%]; P = .14). There were also no statistically significant between-group differences for myocardial infarction, heart failure hospitalization, and atrial fibrillation.CONCLUSIONS AND RELEVANCE: In adults aged 60 years or older, all-cause cardiorespiratory hospitalization was significantly lower with RSVpreF than with no vaccine. The findings suggest potential downstream cardiorespiratory benefits of RSV immunization, although the effect on all-cause cardiovascular hospitalization was not statistically significant.TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT06684743.
AB - IMPORTANCE: Respiratory syncytial virus (RSV) infection is linked to elevated cardiovascular risk, particularly in individuals with preexisting cardiovascular disease (CVD). A bivalent RSV prefusion F protein (RSVpreF) vaccine was recently approved for preventing RSV-related lower respiratory tract illness, but its effectiveness against cardiovascular outcomes has not been evaluated in a randomized trial.OBJECTIVE: To investigate the vaccine effectiveness of RSVpreF compared with no vaccine against cardiovascular outcomes among adults aged 60 years or older.DESIGN, SETTING, AND PARTICIPANTS: Prespecified secondary analysis of the DAN-RSV trial, a pragmatic, open-label, individually randomized clinical trial conducted in Denmark during the 2024-2025 winter season. The first participant was enrolled on November 18, 2024. Adults aged 60 years or older were eligible for inclusion regardless of comorbidity status.INTERVENTIONS: Participants were randomized 1:1 to receive RSVpreF (n = 65 642) or no vaccine (n = 65 634).MAIN OUTCOMES AND MEASURES: Hospitalization for any cardiorespiratory disease was a prespecified secondary outcome, and hospitalizations for any CVD, heart failure, myocardial infarction, stroke, and atrial fibrillation were prespecified exploratory outcomes. Outcomes were assessed from 14 days after booked study visit through May 31, 2025. Vaccine effectiveness was calculated as 1 - incidence rate ratio, expressed as a percentage.RESULTS: Of 131 276 participants included (mean age, 69.4 [SD, 6.5] years; 50.3% male), 28 662 (21.8%) had preexisting CVD. All-cause cardiorespiratory hospitalization incidence was lower in the RSVpreF group compared with the control group (26.3 vs 29.2 events per 1000 participant-years [PY]; absolute rate reduction, 2.90 [95% CI, 0.10-5.71] per 1000 PY; vaccine effectiveness, 9.9% [95% CI, 0.3%-18.7%]; P = .04). There was no significant interaction by baseline CVD status (CVD at baseline: vaccine effectiveness, 5.0% [95% CI, -11.2% to 16.7%]; no CVD at baseline: vaccine effectiveness, 15.2% [95% CI, 2.2%-27.1%]; P = .27 for interaction). For the RSVpreF group vs control group, respectively, incidence rates of all-cause cardiovascular hospitalization were 16.4 vs 17.7 events per 1000 PY (vaccine effectiveness, 7.4% [95% CI, -5.5% to 18.8%]; P = .24), and incidence rates of stroke were 3.0 vs 3.8 events per 1000 PY (vaccine effectiveness, 19.4% [95% CI, -8.6% to 40.4%]; P = .14). There were also no statistically significant between-group differences for myocardial infarction, heart failure hospitalization, and atrial fibrillation.CONCLUSIONS AND RELEVANCE: In adults aged 60 years or older, all-cause cardiorespiratory hospitalization was significantly lower with RSVpreF than with no vaccine. The findings suggest potential downstream cardiorespiratory benefits of RSV immunization, although the effect on all-cause cardiovascular hospitalization was not statistically significant.TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT06684743.
KW - Respiratory syncytial virus
KW - Infection
KW - Mortality
KW - Morbidity
KW - Respiratory Syncytial Virus Vaccines/adverse effects
KW - Atrial Fibrillation/prevention & control
KW - Cardiovascular Diseases/prevention & control
KW - Heart Failure/prevention & control
KW - Humans
KW - Middle Aged
KW - Male
KW - Vaccine Efficacy
KW - Denmark/epidemiology
KW - Respiratory Syncytial Virus Infections/prevention & control
KW - Stroke/prevention & control
KW - Aged, 80 and over
KW - Hospitalization/statistics & numerical data
KW - Female
KW - Aged
KW - Myocardial Infarction/prevention & control
U2 - 10.1001/jama.2025.15405
DO - 10.1001/jama.2025.15405
M3 - Article
C2 - 40884493
SN - 0002-9955
VL - 334
SP - 1431
EP - 1441
JO - JAMA - Journal of the American Medical Association
JF - JAMA - Journal of the American Medical Association
IS - 16
ER -