Abstract Body (Do not enter title and authors here): Background: Influenza vaccination in patients (pts) with acute myocardial infarction (AMI) reduces major adverse cardiac events and is strongly recommendeds. Effective strategies to improve vaccination in high risk pts are needed.

Research Question: Do electronically delivered behavioral nudges improve influenza vaccine uptake in pts withAMI across 3 nationwide randomized implementation clinical trials?

Methods: NUDGE-FLU, NUDGE-FLU-2, and NUDGE-FLU-CHRONIC were randomized, pragmatic, nationwide clinical trials, conducted during the 2022-2023 and 2023-2024 influenza seasons in Denmark. Participants were randomized to either usual care or different behaviourally informed, electronic delivered, letter-based nudges. In a prespecified participant-level pooled meta-analysis, we examined interaction of AMI status on the effects of letter-based nudges vs. usual care. Pooled treatment effects were estimated using binomial regression models with identity link, adjustment for trial, and two-way clustered standard errors at the household and participant levels. Effect modification by recency of AMI as a continuous variable was assessed in restricted cubic spline modeling.

Results: Of 2,146,124 randomizations across all three trials, 59,458 (2.8%) had a history of AMI. Improvement in vaccine uptake was similar in patients with vs. without a history of AMI who received any nudge letter compared with usual care (+1.81 vs. +1.32 percentage points; P_interaction by AMI status=0.09). A letter highlighting the cardiovascular benefits of vaccination (CV-gain frame) resulted in larger improvements in vaccine uptake among patients with (vs. without) a history of AMI (+3.91 vs. +2.03 percentage points; P_interaction by AMI status=0.002). Among patients with AMI, the benefits of the CV-gain frame letter were more pronounced in those not vaccinated in the prior season (+13.7 vs. +1.48 percentage points; P_interaction<0.001). Among younger participants, the CV-gain frame letter was particularly effective in patients with more recent AMI (P_interaction by continuous recency of AMI<0.001).

Conclusion:Across 3 nationwide randomized clinical trials randomizing >2 million Danish citizens, messaging emphasizing the cardiovascular benefits of vaccination improved influenza vaccination uptake, with greater benefits observed in patients with history of AMI. This low-cost, scalable implementation strategy should be considered to close gaps in high-quality cardiovascular care.