Scientific Sessions 2025  /  Influenza and COVID Science  /  Influenza vaccination and risk of cardiovascular events: An instrumental variable analysis of >600,000 participants from the NUDGE-FLU-CHRONIC 1 and 2 trials
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Influenza vaccination and risk of cardiovascular events: An instrumental variable analysis of >600,000 participants from the NUDGE-FLU-CHRONIC 1 and 2 trials

Abstract Body (Do not enter title and authors here): Background: Influenza infection is a transient risk factor for cardiovascular (CV) events. We conducted a prespecified instrumental variable (IV) analysis pooling data from the NUDGE-FLU-CHRONIC and NUDGE-FLU-CHRONIC-2 trials to estimate the causal effect of influenza vaccination on CV outcomes.

Methods: NUDGE-FLU-CHRONIC and NUDGE-FLU-CHRONIC-2 were two identically designed, nationwide, register-based randomized trials conducted in consecutive influenza seasons (2023/2024 and 2024/2025) in Denmark. Both trials included citizens aged 18–64 eligible for free influenza vaccination due to preexisting chronic disease. Participants were randomized 2.45:1:1:1:1:1:1 to usual care or one of six electronic letters deploying behavioral science concepts to promote influenza vaccination. Cardiovascular events were prespecified exploratory outcomes. We used two-stage least squares regression with randomization to any letter as the IV for influenza vaccine uptake.

Results: A total of 608,859 person-seasons from 348,732 unique individuals were included; 170,901 (28.1%) had cardiovascular disease at baseline. Randomization to any letter increased influenza vaccine uptake from 26.0% to 38.0%. COVID-19 vaccine uptake also rose from 17.3% to 27.0%. IV analysis revealed that influenza vaccination significantly reduced the risk of major adverse cardiovascular events (MACE) (absolute risk difference: −0.35%, 95% CI: −0.70% to −0.01%; p = 0.049) and heart failure (−0.23%, 95% CI: −0.45% to −0.01%; p = 0.038), corresponding to number needed to vaccinate (NNV) of 285 and 435, respectively.

Conclusion: In an instrumental variable analysis of >600,000 participants from two implementation trials, we found that influenza vaccination may reduce the risk of CV events in patients with preexisting chronic disease, particularly by lowering heart failure risk. However, due to high concomitant increase in COVID-19 vaccine uptake, the observed effect may reflect a combined effect of influenza and COVID-19 vaccination.
  • Modin, Daniel  ( Department of Cardiology, Copenhagen University Hospital – Herlev and Gentofte , Hellerup , Denmark )
  • Johansen, Niklas  ( Herlev and Gentofte Hospital , Hellerup , Denmark )
  • Angrist, Joshua D.  ( MIT Department of Economics and NBER , Boston , Massachusetts , United States )
  • Yeh, Robert  ( Beth Israel Deaconess Med Ctr , Boston , Massachusetts , United States )
  • Wadhera, Rishi  ( Beth Israel Deaconess Medical Centr , Cambridge , Massachusetts , United States )
  • Vaduganathan, Muthiah  ( Brigham and Womens Hospital , Boston , Massachusetts , United States )
  • Bhatt, Ankeet  ( Kaiser Permanente San Francisco Medical Center & Division of Research , San Francisco , California , United States )
  • Chatur, Safia  ( Brigham and Womens Hospital , Boston , Massachusetts , United States )
  • Claggett, Brian  ( Brigham and Women's Hospital , Boston , Massachusetts , United States )
  • Janstrup, Kira Hyldekær  ( Department of Cardiology, Copenhagen University Hospital – Herlev and Gentofte , Hellerup , Denmark )
  • Larsen, Carsten  ( Department of Clinical Medicine – Department of Infectious Diseases, Aarhus University Hospital , Aarhus , Denmark )
  • Larsen, Lykke  ( Odense University Hospital, Denmark , Odense C , Denmark )
  • Wiese, Lothar  ( Department of Infectious Diseases , Roskilde , Denmark )
  • Dalager-pedersen, Michael  ( Department of Infectious Diseases, Aalborg University Hospital , Aalborg , Denmark )
  • Kober, Lars  ( RIGSHOSPITALET , Copenhagen , Denmark )
  • Solomon, Scott  ( Brigham and Women's Hospital , Boston , Massachusetts , United States )
  • Sivapalan, Pradeesh  ( Respiratory Medicine Section, Department of Medicine, Copenhagen University Hospital – Herlev and Gentofte , Hellerup , Denmark )
  • Jensen, Jens-ulrik Stæhr  ( Respiratory Medicine Section, Department of Medicine, Copenhagen University Hospital – Herlev and Gentofte , Hellerup , Denmark )
  • Martel, Cyril  ( Statens Serum Institut , Copenhagen , Denmark )
  • Krause, Tyra Grove  ( Statens Serum Institut , Copenhagen S , Denmark )
  • Biering-srensen, Tor  ( DEPARTMENT OF CARDIOLOGY GENTOFTE , Charlottenlund , Denmark )
    • Author Disclosures:
    Daniel Modin: DO NOT have relevant financial relationships | Kira Hyldekaer Janstrup: DO NOT have relevant financial relationships Lykke Larsen: DO NOT have relevant financial relationships | Lothar Wiese: DO NOT have relevant financial relationships | Michael Dalager-Pedersen: DO NOT have relevant financial relationships | Lars Kober: DO have relevant financial relationships ; Speaker:Astra Zeneca:Past (completed) ; Speaker:Novo:Past (completed) ; Speaker:Novartis:Past (completed) ; Speaker:Boehringer:Past (completed) | Scott Solomon: DO have relevant financial relationships ; Research Funding (PI or named investigator):Alexion, Alnylam, Applied Therapeutics, AstraZeneca, Bellerophon, Bayer, BMS, Boston Scientific, Cytokinetics, Edgewise, Eidos/BridgeBio, Gossamer, GSK, Ionis, Lilly,NIH/NHLBI, Novartis, NovoNordisk, Respicardia, Sanofi Pasteur, Tenaya, Theracos, US2.AI:Active (exists now) ; Consultant:Abbott, Action, Akros, Alexion, Alnylam, Amgen, Arena, Askbio, AstraZeneca, Bayer, BMS, Cardior, Cardurion, Corvia, Cytokinetics, GSK, Intellia, Lilly, Novartis, Roche, Theracos, Quantum Genomics, Tenaya, Sanofi-Pasteur, Dinaqor, Tremeau, CellProThera, Moderna, American Regent, Sarepta, Lexicon, Anacardio, Akros, Valo, Synhale, Recordati:Active (exists now) | Pradeesh Sivapalan: DO NOT have relevant financial relationships | Jens-Ulrik Stæhr Jensen: No Answer | Cyril Martel: DO NOT have relevant financial relationships | Niklas Johansen: DO NOT have relevant financial relationships | Tyra Grove Krause: DO NOT have relevant financial relationships | Tor Biering-Srensen: No Answer | Joshua D. Angrist: No Answer | Robert Yeh: DO have relevant financial relationships ; Consultant:Abbott Vascular:Active (exists now) ; Research Funding (PI or named investigator):Abbott:Active (exists now) ; Research Funding (PI or named investigator):JenaValve:Active (exists now) ; Research Funding (PI or named investigator):Medtronic:Active (exists now) ; Research Funding (PI or named investigator):Boston Scientific:Active (exists now) ; Research Funding (PI or named investigator):Edwards:Active (exists now) ; Consultant:Edwards:Active (exists now) ; Consultant:Magenta Medical:Active (exists now) ; Consultant:Shockwave:Active (exists now) ; Consultant:Elixir Medical:Active (exists now) ; Consultant:Medtronic:Active (exists now) ; Consultant:CathWorks:Active (exists now) ; Consultant:Boston Scientific:Active (exists now) | Rishi Wadhera: DO have relevant financial relationships ; Consultant:Abbott Vascular:Past (completed) | Muthiah Vaduganathan: DO have relevant financial relationships ; Consultant:American Regent, Amgen, AstraZeneca, Bayer AG, Baxter Healthcare, Bristol Myers Squibb, Boehringer Ingelheim, Chiesi, Cytokinetics, Esperion, Fresenius Medical Care, Idorsia Pharmaceuticals, Lexicon Pharmaceuticals, Merck, Milestone Pharmaceuticals, Novartis, Novo Nordisk, Pharmacosmos, Relypsa, Roche Diagnostics, Sanofi and Tricog Health:Active (exists now) ; Research Funding (PI or named investigator):Amgen, AstraZeneca, Boehringer Ingelheim, Galmed, Novartis, Bayer AG, Occlutech, Pharmacosmos, and Impulse Dynamics:Active (exists now) | Ankeet Bhatt: DO have relevant financial relationships ; Consultant:AstraZeneca:Past (completed) ; Consultant:Merck:Active (exists now) | Safia Chatur: No Answer | Brian Claggett: No Answer
Meeting Info:

Scientific Sessions 2025

2025

New Orleans, Louisiana

Session Info:

Influenza and COVID Science

Monday, 11/10/2025 , 01:30PM - 02:45PM

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