Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Randomized Controlled Trial
. 2025 Feb;18(2):e011496.
doi: 10.1161/CIRCOUTCOMES.124.011496. Epub 2024 Aug 31.

Relative Effectiveness of High-Dose Versus Standard-Dose Quadrivalent Influenza Vaccine in Older Adults With Cardiovascular Disease: A Prespecified Analysis of the DANFLU-1 Randomized Clinical Trial

Jacob Christensen  1   2 , Niklas Dyrby Johansen  1   2 , Daniel Modin  1   2 , Kira Hyldekær Janstrup  1   2 , Joshua Nealon  3 , Sandrine Samson  3 , Matthew Loiacono  4 , Rebecca Harris  5 , Carsten Schade Larsen  6   7 , Anne Marie Reimer Jensen  1   2 , Nino Emanuel Landler  1   2 , Brian L Claggett  8 , Scott D Solomon  9 , Gunnar H Gislason  10 , Lars Køber  11 , Martin J Landray  12   13 , Pradeesh Sivapalan  14   15 , Jens Ulrik Stæhr Jensen  14   15 , Tor Biering-Sørensen  1   2   11   16
Affiliations
Free article
Randomized Controlled Trial

Relative Effectiveness of High-Dose Versus Standard-Dose Quadrivalent Influenza Vaccine in Older Adults With Cardiovascular Disease: A Prespecified Analysis of the DANFLU-1 Randomized Clinical Trial

Jacob Christensen et al. Circ Cardiovasc Qual Outcomes. 2025 Feb.
Free article

Abstract

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 the high-dose quadrivalent influenza vaccine (QIV-HD) versus standard-dose quadrivalent influenza vaccine (QIV-SD) in this prespecified analysis of the DANFLU-1 trial (Feasibility of Randomizing Danish Citizens Aged 65-79 Years to High-Dose Quadrivalent Influenza Vaccine Versus Standard-Dose Quadrivalent Influenza Vaccine in a Pragmatic Registry-Based Setting).

Methods: DANFLU-1 was a pragmatic, open-label, randomized feasibility trial of QIV-HD versus QIV-SD in adults aged 65 to 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, ischemic heart disease, 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 of 71.7±3.9 years and 5877 [47.1%] were female), of whom 2540 (20.4%) had chronic CVD. QIV-HD versus QIV-SD was associated with a lower incidence of hospitalizations for pneumonia or influenza (incidence rate ratio [IRR], 0.30 [95% CI, 0.14-0.64]) and all-cause mortality (IRR, 0.51 [95% CI, 0.30-0.86]) regardless of chronic CVD (Pinteraction=0.57 and 0.49, respectively). The relative effectiveness of QIV-HD versus QIV-SD against all-cause hospitalizations was modified in participants with chronic CVD (overall: IRR, 0.87 [95% CI, 0.76-0.99]; no chronic CVD: IRR, 0.79 [95% CI, 0.67-0.92]; chronic CVD: IRR, 1.11 [95% CI, 0.88-1.39]; Pinteraction=0.026). No other effect modification was observed by the presence of chronic CVD, heart failure, ischemic heart disease, or atrial fibrillation.

Conclusions: The relative effectiveness of QIV-HD versus 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.

Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT05048589.

Keywords: atrial fibrillation; feasibility studies; humans; influenza vaccines; pneumonia.

PubMed Disclaimer

Conflict of interest statement

Dr Nealon was previously employed by Sanofi and may own shares and/or stock options in the company. Drs Samson, Loiacono, and Harris are full-time employees of Sanofi and may own shares and/or stock options in the company. Dr Larsen is chief physician at Danske Lægers Vaccinations Service, part of European LifeCare Group, and has received speaker fees and served on advisory boards for Glaxo Smith Kline, Merck Sharp & Dohme, Pfizer, Takeda, and Valneva. Dr Claggett has received consulting fees from Amgen, Cardurion, Corvia, Myokardia, and Novartis. Dr Solomon has received research grants from Actelion, Alnylam, Amgen, AstraZeneca, Bellerophon, Bayer, Bristol Myers Squibb, Celladon, Cytokinetics, Eidos, Gilead, GSK, Ionis, Lilly, Mesoblast, MyoKardia, National Institute of Health/National Heart, Lung, and Blood Institute, Neurotronik, Novartis, Novo Nordisk, Respicardia, Sanofi, Theracos, Us2.ai and consulted for Abbott, Action, Akros, Alnylam, Amgen, Arena, AstraZeneca, Bayer, Boehringer Ingelheim, BMS, Cardior, Cardurion, Corvia, Cytokinetics, Daiichi Sankyo, GSK, Lilly, Merck, Myokardia, Novartis, Roche, Theracos, Quantum Genomics, Cardurion, Janssen, Cardiac Dimensions, Tenaya, Sanofi, Dinaqor, Tremeau, CellProThera, Moderna, American Regent, Sarepta, Lexicon, Anacardio, Akros, and Puretech Health. Dr Køber has received speaker fees from Novo Nordisk, Novartis, AstraZeneca, Boehringer Ingelheim, and Bayer. Dr Biering-Sørensen is chief investigator of the Boston Scientific Financed DANLOGIC-HF (Danish Pragmatic Randomized Trial to Evaluate the Effect of HeartLogic-Guided Management on Heart Failure Outcomes) trial, the Sanofi Financed NUDGE-FLU (Nationwide Utilization of Danish Government Electronic Letter System for Increasing InFLUenza Vaccine Uptake) trial, the Sanofi Financed DANFLU-1 trial (Feasibility of Randomizing Danish Citizens Aged 65–79 Years to High-Dose Quadrivalent Influenza Vaccine Versus Standard-Dose Quadrivalent Influenza Vaccine in a Pragmatic Registry-Based Setting), the Sanofi Financed DANFLU-2 trial and steering committee member of the Boston Scientific Sponsored LUX-Dx TRENDS Evaluates Diagnostics Sensors in Heart Failure Patients Receiving Boston Scientific’s Investigational Insertable Cardiac Monitor System trial, the Amgen sponsored GALACTIC-HF (A Double-blind, Randomized, Placebo-controlled, Multicenter Study to Assess the Efficacy and Safety of Omecamtiv Mecarbil on Mortality and Morbidity in Subjects With Chronic Heart Failure With Reduced Ejection Fraction) trial, the Boehringer Ingelheim financed EASi-KIDNEY (The Studies of Heart & Kidney Protection With BI 690517 in Combination With Empagliflozin) trial; served on advisory boards for Sanofi, Amgen, Commonwealth Serum Laboratories Seqirus, and GSK; received speaker honorariums from Bayer, Novartis, Sanofi, GE Healthcare, and GSK; received research grants from Boston Scientific, GE Healthcare, AstraZeneca, Novo Nordisk, and Sanofi; and consulted for Novo Nordisk, IQVIA, and Parexel. The other authors report no conflicts.

Comment in

MeSH terms

Associated data