Bhatt Ankeet S, Johansen Niklas Dyrby, Vaduganathan Muthiah, Modin Daniel, Pareek Manan, Chatur Safia, Claggett Brian L, Janstrup Kira Hyldekær, Larsen Carsten Schade, Larsen Lykke, Wiese Lothar, Dalager-Pedersen Michael, Dueger Erica L, Samson Sandrine, Loiacono Matthew M, Harris Rebecca C, Køber Lars, Solomon Scott D, Martel Cyril Jean-Marie, Sivapalan Pradeesh, Jensen Jens Ulrik Stæhr, Biering-Sørensen Tor
Kaiser Permanente San Francisco Medical Center & Division of Research, San Francisco, California.
Stanford University School of Medicine, Palo Alto, California.
JAMA Cardiol. 2025 Jan 1;10(1):78-86. doi: 10.1001/jamacardio.2024.4648.
Influenza vaccination in patients with acute myocardial infarction (AMI) reduces major adverse cardiac events and is strongly recommended in clinical practice guidelines. Effective strategies to improve vaccination are needed in these high-risk patients.
To evaluate whether electronically delivered behavioral nudges improve influenza vaccine uptake in patients with AMI across 3 nationwide implementation randomized clinical trials (RCTs).
DESIGN, SETTING, AND PARTICIPANTS: Nationwide Utilization of Danish Government Electronic Letter System for Increasing Influenza Vaccine Uptake (NUDGE-FLU), Nationwide Utilization of Danish Government Electronic Letter System for Confirming the Effectiveness of Behavioral Nudges in Increasing Influenza Vaccine Uptake Among Older Adults (NUDGE-FLU-2), and Nationwide Utilization of Danish Government Electronic Letter System for Increasing Influenza Vaccine Uptake Among Adults With Chronic Disease (NUDGE-FLU-CHRONIC) were RCTs conducted during the 2022 to 2023 and 2023 to 2024 influenza seasons in Denmark. Participants were randomized to either usual care or various behaviorally informed, electronically delivered, letter-based nudges. In a prespecified participant-level pooled meta-analysis, interaction of AMI status on the effects of letter-based nudges vs usual care was examined. Pooled treatment effects were estimated using binomial regression models with identity link, adjustment for trial, and 2-way clustered SEs at the household and participant levels. Effect modification by recency of AMI as a continuous variable was assessed using restricted cubic spline modeling in NUDGE-FLU-CHRONIC.
Behaviorally informed, electronically delivered, letter-based nudges or usual care.
The primary end point was influenza vaccination receipt.
Of 2 146 124 individual randomizations (mean [SD] age, 71.1 [11.6] years; 1 114 725 female [51.9%]) across all 3 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 for interaction by AMI status = .09). A letter highlighting the cardiovascular benefits of vaccination (ie, cardiovascular-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 for interaction by AMI status = .002). Among patients with AMI, the benefits of the cardiovascular-gain frame letter were more pronounced in those not vaccinated in the prior season (+13.7 vs +1.48 percentage points; P for interaction <.001). Among younger participants with chronic disease, the cardiovascular-gain frame letter was particularly effective in patients with more recent AMI (P for interaction by continuous recency of AMI <.001).
Across 3 nationwide RCTs of Danish citizens, messaging emphasizing the cardiovascular benefits of vaccination improved influenza vaccination uptake, with greater benefits observed in patients with a history of AMI. This low-cost, scalable implementation strategy should be considered to encourage influenza vaccination in high-risk patients.
ClinicalTrials.gov Identifiers: NCT05542004, NCT06030726, NCT06030739.
急性心肌梗死（AMI）患者接种流感疫苗可减少主要不良心脏事件，临床实践指南强烈推荐。这些高危患者需要有效的疫苗接种改善策略。
通过3项全国性实施随机临床试验（RCT）评估电子发送的行为助推是否能提高AMI患者的流感疫苗接种率。
设计、设置和参与者：丹麦政府电子信件系统提高流感疫苗接种率的全国性应用（NUDGE-FLU）、丹麦政府电子信件系统确认行为助推对提高老年人流感疫苗接种率有效性的全国性应用（NUDGE-FLU-2）以及丹麦政府电子信件系统提高慢性病成年人流感疫苗接种率的全国性应用（NUDGE-FLU-CHRONIC）是在丹麦2022至2023年以及2023至2024年流感季节进行的RCT。参与者被随机分为常规护理组或各种基于行为信息、电子发送、以信件形式的助推组。在预先设定的参与者水平汇总荟萃分析中，研究了AMI状态对基于信件的助推与常规护理效果的交互作用。使用具有恒等链接的二项回归模型估计汇总治疗效果，对试验进行调整，并在家庭和参与者水平进行双向聚类标准误分析。在NUDGE-FLU-CHRONIC中，使用受限立方样条模型评估AMI近期情况作为连续变量的效应修正。
基于行为信息、电子发送、以信件形式的助推或常规护理。
主要终点是接种流感疫苗。
在所有3项试验的2146124次个体随机分组中（平均[标准差]年龄，71.1[11.6]岁；1114725名女性[51.9%]），59458人（2.8%）有AMI病史。与常规护理相比，接受任何助推信件的有AMI病史和无AMI病史患者的疫苗接种率改善情况相似（分别为+1.81和+1.32个百分点；AMI状态的交互作用P值 = 0.09）。一封强调疫苗接种心血管益处的信件（即心血管获益框架）使有AMI病史的患者（与无病史患者相比）的疫苗接种率有更大改善（分别为+3.91和+2.03个百分点；AMI状态的交互作用P值 = 0.002）。在有AMI病史的患者中，心血管获益框架信件的益处在前一季未接种疫苗的患者中更为明显（分别为+13.7和+1.48个百分点；交互作用P值<0.001）。在患有慢性病的年轻参与者中，心血管获益框架信件在近期发生AMI的患者中特别有效（AMI连续近期情况的交互作用P值<0.001）。
在针对丹麦公民的3项全国性RCT中，强调疫苗接种心血管益处的信息提高了流感疫苗接种率，在有AMI病史的患者中观察到更大益处。应考虑这种低成本、可扩展的实施策略，以鼓励高危患者接种流感疫苗。
ClinicalTrials.gov标识符：NCT05542004、NCT06030726、NCT06030739。
