Impact of High-Dose Influenza Vaccine on Cardiorespiratory Outcomes in Older Adults: An Updated Systematic Review and Meta-Analysis.

Authors

Larissa Araújo de Lucena, Bezalel Hakkeem, Nathalia Schettino Samad, Gabriel Erzinger, Guilherme Silva Mendes Gaia, Juliana Giorgi, Francesco Stabile, Vitória Martins Prizão, Paulo de Coelho Castro, David Abraham Batista da Hora, Larissa C Hespanhol, Mrunalini Dandamudi, Ferdinand Gilbert Saraiva da Silva Maia, Eveline Pipolo Milan, Martha Gulati

Published in

American journal of preventive medicine. Pages 108598. Oct 08, 2026. Epub Oct 08, 2026.

Abstract

Older adults face an increased risk of influenza-related complications, particularly cardiovascular (CV) events. The comparative effectiveness of high-dose inactivated influenza vaccine (HD-IIV) versus standard-dose inactivated influenza vaccine (SD-IIV) for these outcomes remains uncertain.
Databases including PubMed, Cochrane Library, and Embase were searched from inception through September 2025 for randomized controlled trials (RCTs) comparing HD-IIV with SD-IIV in adults aged ≥ 65 years. Data synthesis was performed using a random-effects model to estimate pooled risk ratios (RRs) with 95% confidence intervals (CIs). Statistical heterogeneity was assessed using the I² statistic and Cochran's Q test.
Six RCTs contributing 593,048 randomizations were included, with 296,754 (50.04%) allocated to HD-IIV. Participants were 53.6% female, and 46.1% had known CV disease. Follow-up ranged from 14 days to 2 years (mean 372 days). HD-IIV was associated with fewer serious cardiorespiratory events (RR 0.92; 95% CI 0.89-0.95), pneumonia events (RR 0.81; 95% CI 0.68-0.96), hospitalizations due to heart failure (HF) (RR 0.87; 95% CI 0.78-0.98), and any respiratory disease (RR 0.93; 95% CI 0.86-1.00). No differences were detected for hospitalization for pneumonia or influenza (RR 0.73; 95% CI 0.50-1.08), MACE (RR 0.94; 95% CI 0.86-1.02), stroke (RR 0.92; 95% CI 0.83-1.02), or hospitalization for coronary events (RR 0.99; 95% CI 0.87-1.12).
In adults aged ≥ 65 years, HD-IIV was associated with modest reductions in serious cardiorespiratory events, pneumonia events, and HF hospitalizations compared with SD-IIV, whereas hospitalization for pneumonia/influenza and broader atherothrombotic CV endpoints did not differ.

PMID:
42849859
Bibliographic data and abstract were imported from PubMed on 09 Oct 2026.

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