Linking Flu Vaccine to Cardiovascular Benefit Could Increase Uptake in Older Adults


In the largest implementation trial ever conducted, new research from the NUDGE FLU trial suggests informing patients of the potential cardiovascular benefits associated with receipt of the flu vaccine could increase uptake among older adults.

Tor Biering-Søreneson, MD, MSc, MPH, PhD Courtesy: American College of Cardiology

Tor Biering-Søreneson, MD, MSc, MPH, PhD
Courtesy: American College of Cardiology

Results of a randomized clinical trial of more than 900,000 older adults in Denmark suggests use of electronic nudges could improve the uptake of influenza and other vaccines.

Named the NUDGE FLU trial, results of the study, which is billed as the largest implementation trial ever conducted, indicate utilizing electronic letters with different nudging strategies could improve uptake of influenza vaccines, with data pointing to a notable increase in uptake when said nudge relayed information on the cardiovascular benefits of vaccination.

“Figuring out ways to increase the percentage of people who get the flu [shot] and other vaccines is important,” said Tor Biering-Sørensen, MD, MSc, MPH, PhD, professor, Center for Translational Cardiology and Pragmatic Randomized Trials, Copenhagen University Hospital, Hellerup, Denmark, and the study’s chief investigator. “Vaccines help prevent infectious diseases and for flu, specifically, many countries lag well behind the WHO recommendation for over 75% of the population to be vaccinated.”

An example of the growing emphasis on implementation science, the NUDGE FLU trial found itself among a bevy of 5 clinical trials pertaining to implementation science being presented as late breaking data at American College of Cardiology 2023 Annual Scientific Session Together With the World Congress of Cardiology. A nationwide, pragmatic, registry-based, randomized implementation trial funded by Sanofi, NUDGE FLU was conducted during the 2022-2023 influenza season in Denmark and included all adultsaged 65 years or older or turning 65 years by January 15, 2023, with the exception of those in nursing homes or those who had an exemption from the mandatory governmental electronic letter system.

Per trial protocol, households included were randomly assigned in a 9:1:1:1:1:1:1:1:1:1 to usual care or one of 9 different electronic letters designed on the basis of different behavioral nudging concepts. Of note, these nudging concepts included priming and hot state activation, depersonalization, gain framing, loss framing, active choice, collective goal, and expert authority and credibility of sender concepts.

Overall, investigators identified 964,870 individuals from 691,820 households for inclusion in the trial. The 964,870-patient cohort represents 78.3% of the entire Denmark population aged 65 years or older. The primary outcome of interest for the trial was the receipt of influenza vaccination on or before January 1, 2023.

Upon analysis, results of the trial indicated influenza vaccination uptake was higher in the groups of patients randomized toreceiving an electronic letter highlighting potential cardiovascular benefits of vaccination (81.00% vs 80.12%; difference, 0.89 percentage points [99.55% CI, 0.29-1.48]; P <.0001) and the group receiving repeated letters at randomization and at day 14 (80.85% vs 80.12%; difference, 0.73 percentage points [0.13-1.34]; P=.0006). Investigators pointed out further analysis suggested this apparent improvement in rates across major subgroups included those with and without cardiovascular disease.

Additionally, subgroup analyses suggested the cardiovascular gain-framed letter used in the trial was “particularly effective” among participants who had not been vaccinated for influenza in the previous season (P=.0002) and sensitivity analysis of all randomly assigned individuals accounting for within-household clustering yielded similar findings.

“As cardiologists, it’s very interesting that just telling people that we can also prevent other downstream issues like cardiovascular outcomes was what worked the best of all the nudge strategies—even better than the reminder, which we expected would be positive,” Biering-Sørensen added. “A lot of studies have shown that people who get the flu vaccine have a lower risk of cardiovascular outcomes, and there may be protective effects [for the heart] that are not specific to flu infection. The flu vaccine may have broader benefits that we don’t yet know.”


  1. Biering-Sørenson T, Johansen ND, Vaduganathan M, et al. Electronic nudges to increase influenza vaccination uptake in Denmark: a nationwide, pragmatic, registry-based, randomised implementation trial. March 2023. doi:
  2. Linking flu vaccination to potential cardiovascular benefits gets more people to roll up their sleeves. American College of Cardiology. Published March 5, 2023. Accessed March 5, 2023.

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