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Influenza vaccine and risk of acute myocardial infarction in a population-based case–control study
  1. Francisco José de Abajo1,2,
  2. Sara Rodríguez-Martín1,2,
  3. Diana Barreira2,
  4. Antonio Rodríguez-Miguel2,
  5. Encarnación Fernández-Antón2,
  6. Miguel Gil3,
  7. Alberto García-Lledó4,5
  1. 1 Biomedical Sciences, Universidad de Alcalá de Henares Facultad de Medicina y Ciencias de la Salud, Alcalá de Henares, Spain
  2. 2 Clinical Pharmacology Unit, Hospital Universitario Príncipe de Asturias, Alcalá de Henares, Spain
  3. 3 Pharmacoepidemiology and Pharmacovigilance, Agencia Espanola de Medicamentos y Productos Sanitarios, Madrid, Spain
  4. 4 Cardiology, Hospital Universitario Principe de Asturias, Alcalá de Henares, Spain
  5. 5 Medicine, Universidad de Alcalá de Henares Facultad de Medicina y Ciencias de la Salud, Alcalá de Henares, Spain
  1. Correspondence to Dr Francisco José de Abajo, Biomedical Sciences, Universidad de Alcala de Henares Facultad de Medicina y Ciencias de la Salud, Alcala de Henares 28805, Madrid, Spain; francisco.abajo{at}


Objective To assess the relationship between influenza vaccination and risk of a first acute myocardial infarction (AMI) in the general population by different epidemic periods.

Methods This is a population-based case–control study carried out in BIFAP (Base de datos para la investigación farmacoepidemiológica en atención primaria), over 2001–2015, in patients aged 40–99 years. Per each incident AMI case, five controls were randomly selected, individually matched for exact age, sex and index date (AMI diagnosis). A patient was considered vaccinated when he/she had a recorded influenza vaccination at least 14 days before the index date within the same season. The association between influenza vaccination and AMI risk was assessed through a conditional logistic regression, computing adjusted ORs (AOR) and their respective 95% CIs. The analysis was performed overall and by each of the three time epidemic periods per study year (pre-epidemic, epidemic and postepidemic).

Results We identified 24 155 AMI cases and 120 775 matched controls. Of them, 31.4% and 31.2%, respectively, were vaccinated, yielding an AOR of 0.85 (95% CI 0.82 to 0.88). No effect modification by sex, age and background cardiovascular risk was observed. The reduced risk of AMI was observed shortly after vaccination and persisted over time. Similar results were obtained during the pre-epidemic (AOR=0.87; 95% CI 0.79 to 0.95), epidemic (AOR=0.89; 95% CI 0.82 to 0.96) and postepidemic (AOR=0.83; 95% CI 0.79 to 0.87) periods. No association was found with pneumococcal vaccine (AOR=1.10; 95% CI 1.06 to 1.15).

Conclusions Results are compatible with a moderate protective effect of influenza vaccine on AMI in the general population, mostly in primary prevention, although bias due to unmeasured confounders may partly account for the results.

  • myocardial infarction
  • epidemiology

Data availability statement

Data are available upon reasonable request.

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Data availability statement

Data are available upon reasonable request.

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  • Contributors Conceptualisation: FJdA, SR-M and AG-L. Data extraction: MG and SR-M. Methodology: FJdA and SR-M. Formal analysis and investigation: SR-M, AR, DB, EF-A, MG, AG-L and FJdA. Writing - original draft preparation: FJdA, AG-L and SR-M. Writing - review and editing: FJdA, SR-M, DB, AR, EF-A, MG and AG-L. Funding acquisition: FJdA and AG-L. Supervision: FJdA. FJdA had full access to all the data in this study and takes complete responsibility for the integrity of the data and the accuracy of the data analysis.

  • Funding This work was supported by research grants from the Biomedical Research Foundation of the University Hospital Príncipe de Asturias (to FJdA and AG-L) and the Institute of Health Carlos III - Ministerio de Ciencia e Innovación (#PI16/01353), cofounded by FEDER (to FJdA). The database BIFAP is fully funded by the Spanish Agency for Medicines and Medical Devices and makes the data available for free to professionals from the academia and the National Health System.

  • Disclaimer The funding sources had no role in study design, collection, analysis and interpretation of data, writing of the report, and in the decision to submit the paper for publication. The results, discussion and conclusions are from the authors and do not necessarily represent the position of their institutions or the Spanish Agency for Medicines and Medical Devices.

  • Competing interests FJdA received an unrestricted research grant from Sanofi Pasteur (a manufacturer of influenza vaccines) for a different project, as well as professional fees from Chiesi, Normon, PENSA and Tecnimede for technical advice in issues different from the present project.

  • Provenance and peer review Not commissioned; internally peer reviewed.

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