Twelve RCTs (23,592 participants) were included in the review. Follow-up durations ranged from one to 12 months. The Cochrane risk of bias tool indicated that five trials were at high risk, one was uncertain risk and six were at low risk of bias (taken from table of characteristics).
Major adverse cardiovascular events (six RCTs): The five published RCTs showed that patients who received flu vaccine had statistically significantly fewer major adverse cardiovascular events compared with placebo or control within one year of follow-up (RR 0.64, 95% CI 0.48 to 0.86; NNT 58); there was no evidence of significant statistical heterogeneity (I²=28%). Subgroup analyses showed that patients with recent acute coronary syndrome (compared to placebo/control) were at lower risk of major adverse cardiovascular events with flu vaccine compared to patients with stable coronary artery disease (compared to placebo/control).
Cardiovascular mortality and all-cause mortality (six RCTs): There were no statistically significant differences between patients who received flu vaccine versus placebo or control in the risk of cardiovascular or all-cause mortality. There was evidence of significant statistical heterogeneity (I²=68%).
Addition of unpublished data and sensitivity analyses did not significantly alter any of the findings. Other findings were reported in the review. There was no evidence of publication bias.