Studies have shown that recent influenza-like infection is a non-traditional cardiovascular disease (CVD) risk factor that has been linked to fatal and non-fatal atherothrombotic events. “There is interest in learning more about the potential association between influenza and subsequent CVD events,” says Jacob A. Udell, MD, MPH, FRCPC.

A Systematic Review & Meta-Analysis

Small, observational randomized clinical trials (RCTs) have suggested that influenza vaccination helps reduce the risk of cardiovascular events, leading several medical associations to recommend universal vaccination in patients with or at risk of CVD. In an issue of JAMA, Dr. Udell and colleagues had a study published that more closely examined the link between flu vaccinations and prevention of cardiovascular events. The systematic review and meta-analysis consisted of RCTs of influenza vaccine that studied cardiovascular events as efficacy or safety outcomes.


For the study, five published RCTs and another unpublished RCT involving more than 6,700 patients in total met inclusion criteria. Analyses were stratified by subgroups of patients with and without a history of acute coronary syndrome (ACS) within 1 year of randomization. Fewer patients treated with the flu vaccine developed a major adverse cardiovascular event when compared with placebo or control groups (2.9% vs 4.7%, respectively). The addition of the unpublished data did not materially change the results.

“The potential impact that this preventive strategy may have
on high-risk CVD patients is significant.”

“The greatest treatment effect was seen among patients with recent ACS,” adds Dr. Udell. In a subgroup analysis of three RCTs of patients with pre-existing coronary artery disease (CAD), the risk of major adverse cardiovascular events among patients with a history of recent ACS was 10.3% for those receiving the flu vaccine, compared with a 23.1% rate seen in placebo or control groups. For patients with stable CAD, corresponding rates were 6.9% and 7.4%, respectively.

Assessing Implications & Looking Ahead

Although the global meta-analysis shows that influenza vaccination appears to lower risks of major adverse cardiovascular events within a year, Dr. Udell says more research is needed. “Our findings have considerable clinical and health policy importance,” he says. “Currently, the flu vaccine is profoundly underused among the general public. The potential impact that this preventive strategy may have on high-risk patients with CVD is significant.”

Greater attention to preventing cardiovascular events is imperative to address the specific pathophysiology underlying influenza, particularly in elderly patients. “In future research, we need to further validate these findings with adequately powered multicenter trials,” says Dr. Udell. “The hope is that we will be able to confirm that flu vaccinations are a low-cost therapy that can be provided annually, safely, and easily to offer greater cardio protection, especially for patients at greatest risk.”