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

INTRODUCTION 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.

Methods

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.

Results

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).

Conclusion

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.