Relative Effectiveness of High-Dose vs. Standard-Dose Quadrivalent Influenza Vaccine in Older Adults with Cardiovascular Disease: A Prespecified Analysis of the DANFLU-1 Randomized Clinical Trial.
Christensen J., Johansen ND., Modin D., Janstrup KH., Nealon J., Samson SI., Loiacono MM., Harris R., Larsen CS., Jensen AMR., Landler NE., Claggett BL., Solomon SD., Gislason GH., Køber L., Landray MJ., Sivapalan P., Jensen JUS., Biering-Sørensen T.
Background: Influenza vaccination reduces the risk of adverse outcomes in patients with cardiovascular disease (CVD). We sought to evaluate whether the presence of CVD modified the relative effectiveness of high-dose (QIV-HD) vs. standard-dose (QIV-SD) quadrivalent influenza vaccine in this prespecified analysis of the DANFLU-1 trial. Methods: DANFLU-1 was a pragmatic, open-label, randomized feasibility trial of QIV-HD vs. QIV-SD in adults aged 65-79 years during the 2021/2022 influenza season in Denmark. Vaccines were allocated in a 1:1 ratio. Baseline and follow-up data regarding diagnoses and mortality were obtained from Danish national registers. The trial is registered at Clinicaltrials.gov: NCT05048589. The CVDs assessed included heart failure (HF), ischemic heart disease (IHD), atrial fibrillation, and a combined group denoted "chronic CVD" consisting of the aforementioned diseases, among others. Prespecified outcomes included hospitalizations for pneumonia or influenza, respiratory disease, CVD, cardiorespiratory disease, all-cause hospitalizations, and mortality. Effect modification was tested using interaction terms. Results: The final study population included 12,477 participants (mean age 71.7±3.9 years, 5,877 (47.1%) female), of whom 2,540 (20.4%) had chronic CVD. QIV-HD vs. QIV-SD was associated with a lower incidence of hospitalizations for pneumonia or influenza (IRR 0.30 (95%-CI 0.14-0.64)) and all-cause mortality (IRR 0.51 (0.30-0.86)) regardless of chronic CVD (p for interaction=0.57 and 0.49, respectively). The relative effectiveness of QIV-HD vs. QIV-SD against all-cause hospitalizations was modified in participants with chronic CVD (Overall: IRR 0.87 (0.76-0.99); no chronic CVD: 0.79 (0.67-0.92); chronic CVD: 1.11 (0.88-1.39); p for interaction=0.026). No other effect modification was observed by the presence of chronic CVD, HF, IHD, or atrial fibrillation. Conclusions: The relative effectiveness of QIV-HD vs. QIV-SD was consistent against hospitalizations for pneumonia or influenza and all-cause mortality regardless of chronic CVD. However, the relative effectiveness against all-cause hospitalizations was modified by the presence of chronic CVD. These results should be considered hypothesis-generating.