Effectiveness of high-dose versus standard-dose influenza vaccines against severe respiratory and cardiovascular outcomes in adults aged >=80 years, Andalusia, Spain, 2024-2025 season

Abstract

Background. Vaccination is a key measure to prevent severe influenza in adults aged [≥]80 years, who experience the highest burden of respiratory and cardiovascular complications. Because immunosenescence reduces the effectiveness of standard-dose vaccines (SD-IIV), enhanced formulations such as high-dose vaccines (HD-IIV) are recommended in the elderly. Real-world data on their effectiveness in adults aged [≥]80 years remain scarce. Aim. To quantify the relative vaccine effectiveness (rVE) of HD-IIV versus SD-IIV in preventing severe influenza disease in adults aged [≥]80 years. Methods. Retrospective, population-based cohort study conducted in Andalusia, Spain, during the 2024-2025 influenza season, including 279,649 vaccinated adults aged [≥]80 years. Data on sociodemographic characteristics, influenza vaccines, chronic diseases and clinical outcomes were taken from the Andalusian health population database. We used a directed acyclic graph to illustrate the assumed relationships between variables. The rVE of HD-IIV versus SD-IIV was estimated using augmented inverse probability weighting models. Results. Compared with SD-IIV, HD-IIV was associated with a lower risk of hospitalization for influenza (rVE=34.0%; 95% CI=15.8-52.2). HD-IIV also showed improved effectiveness against laboratory-confirmed influenza (rVE=43.1%; 95% CI=24.6-61.7), hospitalization for acute myocardial infarction (rVE=26.4%; 95% CI=5.6-47.2), for stroke (rVE=32.9%; 95% CI=17.4-47.4), for pulmonary embolism (rVE=26.7%; 95% CI=0.7-52.6) and for overall cardiovascular outcomes (rVE=6.6%; 95% CI=0.9-12.2). No association was observed for hospitalization due to pneumonia, influenza/pneumonia, heart failure, respiratory outcomes, or in-hospital mortality. Conclusion. Among adults aged [≥]80 years, HD-IIV was more effective than SD-IIV in preventing hospitalization for influenza and severe cardiovascular outcomes, supporting its use in this at-risk population.

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