Influenza Vaccination and Cardiovascular Outcomes in High-Risk Patients

Key Takeaways

• Influenza vaccination was associated with lower all-cause mortality and lower cardiovascular mortality in patients with ischemic heart disease or heart failure.
• Myocardial infarction risk was lower in vaccinated patients, whereas stroke and major adverse cardiovascular events were not significantly different.
• Reconstructed individual data showed a stronger mortality signal, greatest within four months after vaccination, with findings reported as consistent across age, disease type, study design, and follow-up duration.

In an updated meta-analysis of patients with ischemic heart disease or heart failure, influenza vaccination was associated with lower all-cause mortality, with an HR of 0.72 and a 95% CI of 0.63 to 0.82. The analysis focused on a high cardiovascular risk population that included randomized and observational evidence. Across the pooled dataset, mortality reduction was the leading finding.

The review was an updated systematic review and meta-analysis that included 23 studies, comprising 7 randomized controlled trials and 16 observational studies, with 1,137,377 participants. Investigators defined the high-risk population as patients with ischemic heart disease or heart failure. They used 2 complementary analytic approaches, including a reconstructed individual patient data meta-analysis for the primary outcome and study-level random-effects meta-analyses for all outcomes. Pooled hazard ratios were estimated with Cox models around cardiovascular outcomes after influenza vaccination.

For pooled secondary outcomes, cardiovascular mortality was lower among vaccinated patients, with an HR of 0.77 and a 95% CI of 0.67 to 0.89. Myocardial infarction was also less frequent, with an HR of 0.81 and a 95% CI of 0.78 to 0.83. Stroke showed an HR of 0.88 with a 95% CI of 0.68 to 1.14, and major adverse cardiovascular events showed an HR of 0.81 with a 95% CI of 0.57 to 1.15. Mortality and myocardial infarction associations were separated from the non-significant stroke and composite endpoint findings.

Reconstructed individual patient data from 22,443 participants showed a 38% mortality reduction, corresponding to an HR of 0.62 with a 95% CI of 0.57 to 0.67. The greatest benefit was reported in the first 4 months after vaccination. Investigators described the effect as consistent across age, disease type, study design, and follow-up duration. Heterogeneity was explored with subgroup, sensitivity, and meta-regression analyses.

Study quality was assessed with RoB 2 for randomized trials and ROBINS-I for observational studies. The authors interpreted the findings as showing lower mortality and cardiovascular protection after influenza vaccination in patients with ischemic heart disease or heart failure. They also framed annual vaccination as a secondary prevention strategy within this population. The overall interpretation remained centered on mortality and cardiovascular outcomes in the pooled evidence.