Association Between Influenza Vaccination and Cardiovascular Outcomes in High-Risk Patients: A Meta-Analysis

Study Questions:

Do influenza vaccinations impact cardiovascular outcomes among high-risk patients?


This was a systematic review and meta-analysis, based on a literature search in MEDLINE (1946-August 2013), EMBASE (1947-August 2013), and the Cochrane Library Central Register of Controlled Trials (inception-August 2013). A total of 2,189 articles were screened for eligibility and identified 71 potentially relevant studies reviewed. After excluding 59 studies, 12 randomized clinical trials (RCTs) met inclusion criteria for the final meta-analysis. Among the six placebo or control RCTs, 1,753 patients were randomly assigned to receive one intramuscular injection of standard influenza vaccination, 1,620 to receive a live, intranasal attenuated vaccine, 1,375 to receive intramuscular placebo, 1,622 to receive intranasal placebo, and 365 to receive no treatment. Five trials were previously published, and one trial is unpublished. The study population had to include patients at high risk of cardiovascular disease, and report cardiovascular outcomes either as efficacy or safety events. Random-effects Mantel-Haenszel risk ratios (RRs) and 95% confidence intervals (CIs) were derived for composite cardiovascular events, cardiovascular mortality, all-cause mortality, and individual cardiovascular events. Analyses were stratified by subgroups of patients with and without a history of acute coronary syndrome (ACS) within 1 year of randomization.


A total of five published and one unpublished RCT were included, with 6,735 patients (mean age, 67 years; 51.3% women; 36.2% with a cardiac history; mean follow-up time, 7.9 months). Influenza vaccine was associated with a lower risk of composite cardiovascular events (2.9% vs. 4.7%; RR, 0.64 [95% CI, 0.48-0.86]; p = 0.003) in published trials. A treatment interaction was detected between patients with (RR, 0.45 [95% CI, 0.32-0.63]) and without (RR, 0.94 [95% CI, 0.55-1.61]) recent ACS (p for interaction = 0.02). Results were similar with the addition of unpublished data.


The investigators concluded that in this meta-analysis, the use of influenza vaccine was associated with a lower risk of major adverse cardiovascular events. The greatest treatment effect was seen among the highest-risk patients with more active coronary disease. A large, adequately powered, multicenter trial is warranted to address these findings and assess individual cardiovascular endpoints.


Currently, influenza vaccination is underutilized among patients with cardiovascular disease. These data support the use of vaccination, particularly in high-risk patients.

Clinical Topics: Acute Coronary Syndromes, Dyslipidemia, Prevention, Nonstatins, Novel Agents, Statins

Keywords: Odds Ratio, Acute Coronary Syndrome, Influenza, Human, Pneumonia, Follow-Up Studies, Influenza Vaccines, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Risk Factors, Vaccines, Attenuated, Injections, Intramuscular, Cardiovascular Diseases, Confidence Intervals, Vaccination

< Back to Listings