High-dose quadrivalent influenza vaccine reduced cardio-respiratory hospitalization (OR 0.93) and cardiovascular hospitalization (OR 0.93) compared to standard-dose vaccine in older adults.
Meta-Analysis (n=511,890)
Mixed (open-label and modified double-blind)
Yes
Does high-dose quadrivalent influenza vaccine reduce cardio-respiratory and cardiovascular hospitalizations in adults aged 65 years or older?
High-dose quadrivalent influenza vaccine modestly but significantly reduces cardio-respiratory and cardiovascular hospitalizations, including heart failure, compared to standard-dose vaccine in older adults.
Effect estimate: OR 0.93 (95% CI 0.90-0.97)
p-value: p=0.0004
Older adults remain highly vulnerable to serious influenza-related complications despite routine vaccination. Whether high-dose quadrivalent influenza vaccine (HD-QIV) offers greater protection than standard-dose quadrivalent influenza vaccine (SD-QIV) against clinically important outcomes remains an important question. We conducted a systematic review and pairwise meta-analyses of randomized controlled trials (RCTs) comparing HD-QIV with SD-QIV in adults aged 65 years or older. PubMed, Cochrane Library, Embase, Web of Science, and Scopus were searched up to February 2026. Odds ratios (ORs) with 95% confidence intervals (CIs) were pooled using random-effects models. Prespecified subgroup analyses were performed according to baseline cardiovascular disease (CVD) status. Four RCTs comprising 511,890 participants were included. HD-QIV was associated with significantly lower odds of cardio-respiratory hospitalization (OR 0.93, 95% CI 0.90–0.97) and cardiovascular hospitalization (OR 0.93, 95% CI 0.89–0.98), with no significant reduction in respiratory hospitalization (OR 0.90, 95% CI 0.80–1.01). Significant reductions were also observed for hospitalization due to influenza (OR 0.61, 95% CI 0.50–0.74), laboratory-confirmed influenza hospitalization (OR 0.69, 95% CI 0.56–0.86), and heart failure hospitalization (OR 0.80, 95% CI 0.69–0.94). No significant differences were found for all-cause hospitalization (P = 0.12), all-cause mortality (P = 0.413), myocardial infarction (P = 0.753), or serious adverse events (P = 0.419). No significant subgroup differences were observed according to baseline CVD status. In older adults, HD-QIV was associated with modest but significant reductions in cardio-respiratory and cardiovascular hospitalization, as well as influenza-related and heart failure hospitalizations, without an apparent safety penalty. These findings support preferential use of high-dose influenza vaccination in this population.
Elgendy et al. (Sat,) conducted a meta-analysis in Older adults with or without cardiovascular risk (n=511,890). High-dose quadrivalent influenza vaccine (HD-QIV) vs. Standard-dose quadrivalent influenza vaccine (SD-QIV) (15 µg hemagglutinin per strain) was evaluated on Cardio-respiratory hospitalization (OR 0.93, 95% CI 0.90-0.97, p=0.0004). High-dose quadrivalent influenza vaccine reduced cardio-respiratory hospitalization (OR 0.93) and cardiovascular hospitalization (OR 0.93) compared to standard-dose vaccine in older adults.