Mortality and Morbidity Benefit After Influenza Vaccination in High Cardiovascular Risk Population: a Systematic Review and Meta-analysis

Influenza infection increases cardiovascular risk in patients with ischemic heart disease (IHD) or heart failure (HF). This updated meta-analysis evaluated the cardiovascular benefits of influenza vaccination in these populations. Two complementary approaches were used: an individual patient data (IPD) meta-analysis for the primary outcome (reconstructed from published Kaplan–Meier curves) and conventional study-level random-effects meta-analyses for all outcomes. Cox models were used to estimate pooled hazard ratios (HRs). Heterogeneity was explored using subgroup, sensitivity, and meta-regression analyses, and study quality was assessed with RoB 2 and ROBINS-I. Twenty-three studies (7 RCTs, 16 observational; n = 1,137,377) met inclusion criteria. Influenza vaccination significantly reduced all-cause mortality (HR = 0.72; 95% CI: 0.63 to 0.82) and cardiovascular mortality (HR = 0.77; 95% CI: 0.67 to 0.89). Vaccinated patients also had a lower risk of MI (HR = 0.81; 95% CI: 0.78 to 0.83), whereas effects on stroke (HR = 0.88; 95% CI: 0.68 to 1.14) and MACE (HR = 0.81; 95% CI: 0.57 to 1.15) were not significant. Reconstructed individual data (n = 22,443) demonstrated a 38% mortality reduction (HR = 0.62; 95% CI: 0.57 to 0.67), with the greatest benefit in the first four months postvaccination. Effects were consistent across age, disease type, study design, and follow-up duration. In conclusion, Influenza vaccination markedly lowers mortality and provides cardiovascular protection in patients with IHD or HF, supporting annual vaccination as an effective secondary prevention strategy.