Influenza Vaccination and Cardiovascular Risk

Quick Takes

  • This is a meta-analysis of six randomized clinical trials including 9,001 adults who were randomized to influenza vaccination vs. matching placebo or standard care, examining the association between influenza vaccination and CV events.
  • 3.6% of vaccinated patients developed a major CV event within 12 months of vaccination vs. 5.4% of those who received placebo or control. The number needed to treat to prevent one CV event with influenza vaccination was 56.
  • In subgroup analyses, the benefit appears to be strongest in patients who had a recent acute coronary syndrome.

Study Questions:

Is seasonal influenza vaccination associated with lower rates of adverse cardiovascular (CV) events?


This is an updated meta-analysis examining the association between influenza vaccination and CV events that incorporates a recently published clinical trial in patients with recent acute coronary syndrome (ACS). Clinical trials published between 2000 and 2021 that randomized participants (outpatients or inpatients) to either influenza vaccine or placebo/control were included. Subgroup analysis was performed examining the association in stable outpatients and those who had a recent ACS. The primary outcome was a composite of CV death or hospitalization for myocardial infarction, unstable angina, stroke, heart failure, or urgent coronary revascularization within 12 months of vaccination. The secondary outcome was CV mortality.


Six published randomized controlled trials comprising a total of 9,001 patients were included (mean age, 65.5 years; 42.5% women; 52.3% with a cardiac history), of whom 4,510 received the influenza vaccine (2,890 in intramuscular form, 1,620 in intranasal form). Overall, influenza vaccine was associated with a lower risk of composite CV events (3.6% vs. 5.4%; relative risk [RR], 0.66; 95% confidence interval [CI], 0.53-0.83; p < 0.001). The association was significant only in patients with recent ACS (RR, 0.55; 95% CI, 0.41-0.75), and not stable outpatients (RR, 1.00; 95% CI, 0.68-1.47) (p for interaction = 0.02). Findings were similar for CV mortality.


Influenza vaccination is overall associated with lower CV events, with a notably significant effect of 45% lower risk in individuals with recent ACS.


This updated meta-analysis (initial one in 2013) incorporates data from the most recent trial, IAMI (Influenza Vaccination After Myocardial Infarction), which randomized 2,532 patients with a recent ACS to influenza vaccination or placebo and showed a lower risk of CV events. Despite the early interruption of the IAMI trial due to the COVID-19 pandemic, its findings were consistent with the initial meta-analysis in 2013, which had suggested that patients with a recent ACS are the ones that benefit most from influenza vaccination. Studying the impact of influenza vaccination on outcomes is challenging due to the seasonal variation in the circulating strains of the influenza virus. Nevertheless, findings have now been consistent across several trials and time frames. The mechanism through which vaccination decreases CV risk is likely twofold: first through preventing acute inflammation related to the infection itself, and second through activation of immune pathways that lead to an overall lowering of pro-inflammatory cytokines—which is likely more relevant in patients with recent ACS who have rampant inflammation.

Clinical Topics: Acute Coronary Syndromes, Cardiac Surgery, COVID-19 Hub, Heart Failure and Cardiomyopathies, Invasive Cardiovascular Angiography and Intervention, Prevention, Cardiac Surgery and Arrhythmias, Cardiac Surgery and Heart Failure, Acute Heart Failure, Interventions and ACS

Keywords: Acute Coronary Syndrome, Angina, Unstable, COVID-19, Heart Disease Risk Factors, Heart Failure, Influenza Vaccines, Influenza, Human, Myocardial Infarction, Myocardial Ischemia, Myocardial Revascularization, Primary Prevention, Risk Factors, Stroke, Vaccination

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