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Am Fam Physician. 2016;93(5):357-358

Related POEM: Influenza Vaccine Reduces Risk of Adverse Cardiovascular Events in High-Risk Patients.

Author disclosure: No relevant financial affiliations.

Clinical Question

Does influenza vaccination have any benefit for primary or secondary prevention of cardiovascular disease?

Evidence-Based Answer

Influenza vaccination may reduce cardiovascular mortality in patients with established cardiovascular disease. The effect of vaccination is unclear among patients in the general population without known cardiovascular disease. (Strength of Recommendation: A, based on consistent, good-quality patient-oriented evidence.)

Practice Pointers

Globally, cardiovascular disease remains the number one cause of death.1 By 2030, it is estimated that the number of annual deaths from cardiovascular disease will increase to 23.3 million.1 Innovative strategies for primary and secondary prevention of cardiovascular disease are important. Observational studies have shown an association between receipt of the influenza vaccine and lower cardiovascular morbidity and mortality, especially among older and vulnerable populations.2,3 Another study found that influenza infection, but not influenza vaccination, was associated with an increased risk of cardiovascular events.4

This Cochrane review included eight randomized controlled trials with 12,029 participants 18 years or older. Interventions included influenza vaccine administered by any route at any dosage vs. a saline infusion or no intervention. Four trials (n = 10,347) focused on influenza prevention in the general and older populations and reported cardiovascular outcomes in their safety analyses. Two of these studies (n = 5,267) included adults 18 to 60 years of age, whereas the other two studies (n = 5,080) included participants 60 to 98 years of age. A minority of these patients had diabetes mellitus or undefined cardiac disease, and one-half of the patients in one of the studies had hypertension. Four trials (n = 1,682) focused on prevention of cardiovascular events in patients of varying ages with established coronary heart disease, including participants with acute myocardial infarction. These populations were analyzed separately. Primary outcomes included myocardial infarction, unstable angina, and death from cardiovascular causes. Follow-up durations ranged from 42 days to one year.

Overall, study quality was high. Three primary prevention trials and two secondary prevention trials were deficient in three or more risk of bias criteria. The four secondary prevention trials reported significant reductions in cardiovascular mortality with influenza vaccination (relative risk = 0.45; 95% confidence interval, 0.26 to 0.76). Although three of the four primary prevention studies reported cardiovascular mortality, cardiovascular events were too scarce to allow the authors to draw conclusions.

Another systematic review that examined the effect of influenza vaccination on cardiovascular outcomes found no effect on cardiovascular mortality, but it did find a reduction in a composite outcome of cardiovascular events among those receiving influenza vaccination. This effect was greatest in those with established cardiovascular disease.2 Although data regarding the benefit of influenza vaccination for primary prevention of cardiovascular disease are inconclusive, current U.S. guidelines recommend routine vaccination for all adults without contraindications,5 and international guidelines recommend annual vaccination for patients with chronic heart disease.6

These are summaries of reviews from the Cochrane Library.

This series is coordinated by Corey D. Fogleman, MD, assistant medical editor.

A collection of Cochrane for Clinicians published in AFP is available at

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