Impact of Influenza Vaccination on Mortality and Major Cardiovascular Events in Adults with Cardiovascular Disease: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Background: Cardiovascular disease (CVD) is a leading cause of morbidity and mortality worldwide, and seasonal influenza is a recognized trigger of acute cardiovascular events. The influenza vaccine has been proposed as a secondary preventative measure, though the benefits regarding mortality and cardiovascular events are unclear. Objective: This study aimed to establish the efficacy of influenza vaccination in lowering mortality and major cardiovascular events in adults suffering from established CVD. Methods: A systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted. Eligible studies were identified from PubMed, Google Scholar, and The Cochrane Central Register of Controlled Trials (CENTRAL) through November 2025. RCTs involving adults with established CVD evaluating influenza vaccine impact in comparison to placebo or standard care were included. The Cochrane Risk of Bias tool 2 was used to evaluate study quality. Results: A total of eight RCTs met the inclusion criteria. Influenza vaccination was associated with a statistically significant decrease in the composite outcome (of all-cause mortality, acute myocardial infarction, and stent thrombosis) (OR 0.71, 95% CI 0.57–0.90; p = 0.004; I2 = 0%) and major adverse cardiovascular events (OR 0.44, 95% CI 0.26–0.74; p = 0.002; I2 = 0%). Cardiovascular mortality was found to be significantly lower in the vaccination group (OR 0.64, 95% CI 0.47–0.86; p = 0.003). However, all-cause mortality was not significantly reduced (OR 1.13, 95% CI 0.79–1.62; p = 0.50; I2 = 88%). Conclusions: Influenza vaccination was associated with a reduction in combined cardiovascular events and mortality due to cardiovascular causes in adults diagnosed with established CVD. In contrast, all-cause mortality was not significantly reduced, and the evidence for this outcome was inconclusive. This supports the routine use of the vaccine as an adjunctive measure in the secondary prevention of CVD.