Two types of electronically delivered letter strategies — a letter highlighting potential cardiovascular benefits of influenza vaccination and a repeat reminder letter — increased flu shot uptake compared to usual care alone, in a national study of seniors in Denmark.

And in a prespecified subanalysis focusing on older adults with cardiovascular disease (CVD), these two strategies were also effective in boosting vaccine uptake in those with or without CVD.

The findings are from the Nationwide Utilization of Danish Government Electronic Letter System for Increasing InFLUenza Vaccine Uptake (NUDGE-FLU) trial, which compared usual care alone with one of nine different electronic letter “behavioral nudge” strategies during the 2022-23 flu season in people age 65 years and older.  

Niklas Dyrby Johansen, MD, Hospital–Herlev and Gentofte and Copenhagen University, Denmark, presented the main study findings in a late-breaking clinical trial session at the American College of Cardiology (ACC) Scientific Session/World Congress of Cardiology (WCC) 2023, and the article was simultaneously published in The Lancet.

The subanalysis in patients with CVD was published online March 5 in Circulation.

“Despite modest effect sizes, the results may have important implications when translated to a population level,” Dyrby Johansen concluded during his presentation. Still, the authors write, “the low-touch (no person-to-person interaction), inexpensive, and highly scalable nature of these electronic letters might have important population-level public health implications.”  

They note that among approximately 63 million Medicare beneficiaries in the United States, a 0.89–percentage point absolute increase in vaccination rate achieved through the most successful electronic letter in NUDGE-FLU, the one highlighting cardiovascular gain, would be expected to lead to 500,000 additional vaccinations and potentially prevent 7849 illnesses, 4395 medical visits, 714 hospitalizations, and 66 deaths each year.

Electronic letter systems similar to the one used in this trial are already in place in several European countries, including Sweden, Norway, and Ireland, the researchers note.

In countries such as the United States, where implementing a nationwide government electronic letter system might not be feasible, nudges could be done via email, text message, or other systems, but whether this would be as effective remains to be seen.

Commenting on the findings, David Cho, MD, UCLA Health, and chair of the ACC Health Care Innovation Council, commended the researchers on engaging patients with more than a million separate nudges sent out during one flu season, and randomly assigning participants to 10 different types of nudges, calling it “impressive.”

“I think the concept that the nudge is to plant an idea that leads to an action is pretty much the basis of a lot of these healthcare interventions, which seems like a small way to have a big impact at outcome,” Cho noted. “The behavioral science aspect of the nudges are also fascinating to me personally, and I think to a lot of the cardiologists in the audience, about how you actually get people to act. I think it’s been a lifelong question for people in general, how do you get people to follow through on an action?”

“So I found the fact that secondary gain from a cardiovascular health standpoint, but also the repeated nudges were sort of simple ways that you could have people take ownership and get their flu vaccination,” he said.

“This is ACC, this is a cardiovascular conference, but the influence of vaccine is not just a primary care problem, it is also directly affecting cardiovascular disease,” Cho concluded.

“Small but Important Effect”

In an accompanying editorial, Melissa Stockwell, MD, Columbia University, New York, writes, “The study by Johansen and colleagues highlights the small but still important effect of scalable, digital interventions across an entire at-risk population.”

A difference of 0.89% in the entire study population of over 960,000 adults age 65 years or older would be more than 8500 additional adults protected, she notes. “That increase is important for a scalable intervention that has a low cost per letter.”

Moreover, “that the cardiovascular gain-framed messages worked best in those who had not been vaccinated in the previous season further highlights the potential impact on a more vaccine-hesitant population,” Stockwell notes. 

However, with the mandatory government electronic notification system in Denmark, “notifications are sent via regular email and SMS message, and recipients log in through a portal or smartphone app to view the letter.” Similar studies in the United States that included this extra step of needing to sign in online have not been effective in older populations.

Another limitation is that the intervention may have a different effect in populations for which there is a digital divide between people with or without Internet access of sufficient data on their mobile phones.

First-of-Its Kind, Nationwide Pragmatic Trial

The NUDGE-FLU protocol was previously published in the American Heart Journal. NUDGE-FLU is a first-of-its kind nationwide, pragmatic, registry-based cluster-randomized implementation trial of electronically delivered nudges to increase influenza vaccination uptake, the researchers note.

They identified 964,870 individuals who were 65 years or older (or would turn 65 by January 15, 2023) who lived in one of 691,820 households in Denmark.

This excluded individuals who lived in a nursing home or were exempt from the government’s mandatory electronic letter system that is used for official communications.

Households were randomly assigned 9:1:1:1:1:1:1:1:1:1 to receive usual care alone or along with one of nine electronic letter strategies based on different behavioral science approaches to encourage influenza vaccination uptake:

1. Standard electronic letter

2. Standard electronic letter sent at randomization and again 14 days later (repeated letter)

3. Depersonalized letter without the recipient’s name

4. Gain-framing nudge (“Vaccinations help end pandemics, like COVID-19 and the flu. Protect yourself and your loved ones.”)

5. Loss-framing nudge (“When too few people get vaccinated, pandemics from diseases like COVID-19 and the flu can spread and place you and your loved ones at risk.”)

6. Collective-goal nudge (“78% of Danes 65 and above were vaccinated against influenza last year. Help us achieve an even higher goal this year.”)  

7. Active choice or implementation-intention prompt (“We encourage you to record your appointment time here.”)

8. Cardiovascular gain–framing nudge (“In addition to its protection against influenza infection, influenza vaccination also seems to protect against cardiovascular disease such as heart attacks and heart failure.”)

9. Expert-authority statement (“I recommend everyone over the age of 65 years to get vaccinated against influenza — Tyra Grove Krause, Executive Vice President, Statens Serum Institut.”)

The electronic letters were sent out September 16, 2022, and the primary endpoint was vaccine receipt on or before January 1, 2023.

All individuals received an informative vaccination encouragement letter from the Danish Health Authority (usual care) delivered via the same electronic letter system during September 17 through September 21, 2022. 

The individuals had a mean age of 73.8 years, 51.5% were women, and 27.4% had chronic cardiovascular disease.

The analyses were done in one randomly selected individual per household.

Influenza vaccination rates were significantly higher in the cardiovascular gain–framing nudge group vs usual care (81.00% vs 80.12%; difference, 0.89 percentage points; P < .0001) and in the repeat letter group vs usual care (80.85% vs 80.12%; difference, 0.73 percentage points; P = .0006).

These two strategies also improved vaccination rates across major subgroups.

The cardiovascular gain–framed letter was particularly effective among participants who had not been vaccinated for influenza in the previous season.

The seven other letter strategies did not increase flu shot uptake.

Subanalysis in CVD

In the prespecified subanalysis of the NUDGE-FLU trial of patients age 65 and older that focused on patients with CVD, Daniel Modin, MB, and colleagues report that 83.1% of patients with CVD vs 79.2% of patients without CVD received influenza vaccination within the requested time (P < .0001).

The two nudging strategies — a letter highlighting potential cardiovascular benefits of influenza vaccination or a repeat letter — that were effective in boosting flu shot rates in the main analysis were also effective in all major CVD subgroups (ischemic heart disease, pulmonary heart disease, heart failure, atrial fibrillation, cerebrovascular disease, atherosclerotic CVD, embolic or thrombotic disease, and congenital heart disease).

Despite strong guideline endorsement, “influenza vaccination rates remain suboptimal in patients with high -risk cardiovascular disease,” Morin and colleagues write, possibly due to “insufficient knowledge among patients and providers of potential clinical benefits, concerns about vaccine safety, and other forms of vaccine hesitancy.”

Their findings suggest that “select digital behaviorally informed nudges delivered in advance of vaccine availability might be utilized to increase influenza vaccinate uptake in individuals with cardiovascular disease.”

NUDGE-HF was funded by Sanofi. Johansen and Modin have no disclosures. The disclosures of the other authors are listed with the articles. Stockwell has no disclosures.

American College of Cardiology (ACC) 2023 Annual Scientific Session. Late Breaking Clinical Trials III. Presented March 5, 2023.

Lancet. Published online March 5, 2023. Full Text, Editorial

Circulation. Published online March 5, 2023. Abstract

Am Heart J. Published online February 17, 2023. Full text

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