Effect of Influenza Vaccination on Major Cardiovascular Events and Mortality: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Cardiovascular disease remains the leading global cause of mortality despite advances in preventive therapies. Influenza infection is increasingly recognized as a trigger for acute cardiovascular events, prompting interest in influenza vaccination as a potential cardioprotective intervention in high-risk patients. We aimed to conduct a systematic review and meta-analysis to evaluate the effect of influenza vaccination on cardiovascular outcomes in adults with established cardiovascular disease. PubMed, Embase, and Cochrane databases were systematically searched using relevant keywords from inception until October 2025. Seven studies were included after the final screening. Outcomes were reported as all cause mortality, myocardial infarction, major adverse cardiovascular events and heart failure related hospitalization. Interstudy heterogeneity was assessed using I² and X² statistics. Statistical calculations were performed using Review Manager 5.4.1, with a p-value of < 0.05 indicating statistical significance. Seven randomized controlled trials including 12, 224 participants were analyzed. Influenza vaccination significantly reduced major adverse cardiovascular events and cardiovascular mortality. A borderline reduction was observed for myocardial infarction and all-cause mortality. No significant differences were found for stroke, coronary revascularization, or heart failure–related hospitalization. Heterogeneity was low for most primary outcomes. The routine use of influenza vaccination as an effective adjunctive strategy in secondary cardiovascular prevention is supported by the fact that it significantly lowers cardiovascular mortality and major cardiovascular events in patients with established heart disease.