More Data Showing Flu Vaccine Lowers CVD Risk

October 22, 2013

TORONTO, ON — Winter is coming, specifically the flu season, and very few North Americans get vaccinated, despite accumulating data suggesting that an annual flu shot can protect against cardiovascular disease events, particularly in high-risk individuals with existing coronary heart disease.

The latest report, from a meta-analysis of six randomized, controlled clinical trials that included 6735 patients, showed that influenza vaccination was associated with a 36% lower risk of cardiovascular events[1]. The influenza vaccine was associated with 55% lower risk of major adverse cardiovascular events in patients with a recent acute coronary syndrome (ACS).

In these ACS patients, investigators say just eight patients would need to be treated with the influenza vaccine to prevent one major cardiovascular event.

Dr Jacob Udell (University of Toronto, ON) led the review, which is published in the October 23, 2013 issue of the Journal of the American Medical Association and has previously published studies showing an association between the influenza vaccine and cardiovascular outcomes. He previously told heartwire that he is fully behind vaccination to lower cardiovascular risk and that most doctors either don't believe the data or are concerned about the short-term side effects, such as flulike symptoms or a sore arm.

"Influenza vaccination may prevent cardiovascular events via avoidance of atherosclerotic plaque rupture or other forms of cardiac injury in a vulnerable patient and represents a simple, annual protective therapy to reduce cardiovascular events," write Udell and colleagues. "This finding has considerable clinical and health-policy importance, given the profound underuse of vaccination among the general public and the potential impact this preventive strategy may have on high-risk patients."

Vaccine Benefits ACS Patients Most

With the lack of gold-standard clinical trials testing the hypothesis that vaccination can lower the risk of cardiovascular disease, the researchers conducted a systematic review and meta-analysis of randomized trials comparing influenza vaccination with placebo or control in patients at high risk for cardiovascular disease. Five published studies, including FLUVACS and FLUCAD , and one unpublished study were included in the analysis. The studies included a mix of patients with recent ACS and stable coronary disease.

Overall, major cardiovascular events, defined as a composite of cardiovascular death, hospitalization for MI, unstable angina, stroke, heart failure, or urgent revascularization, occurred in 2.9% of the 3238 patients treated with the vaccine and 4.7% of the 3231 patients treated with placebo/control (relative risk [RR] 0.64; 95% CI 0.48–0.86). This translated into a number needed to treat of 58 to prevent one event.

In the 789 ACS patients, major cardiovascular events occurred in 10.25% of patients treated with the vaccine and 23.1% of those treated with placebo (RR 0.45; 95% CI 0.32–0.63). When analyzed separately, the reduction in risk among the stable coronary artery disease patients was not statistically significant (RR 0.94; 95% CI 0.55–1.61).

The researchers say the mechanisms underlying acute influenza infection and cardiovascular risk are not clear right now, but the evidence supporting an association between the two is considerable. They add that even though the recent flu outbreak of 2012–2013 is a good reminder of potential cardiovascular complications that can occur in association with respiratory infections, less than one-third of North Americans and less than 50% of high-risk patients get vaccinated each year.

Efficacy Warrants Use

In an editorial[2], Dr Kathleen Neuzil (Vaccine Access and Delivery PATH, Seattle, WA) said that as with all meta-analyses, the findings are limited by the quality of the underlying studies and that association does not imply causation. "Regardless of whether influenza vaccine reduces cardiovascular disease, the known morbidity of influenza in older adults with and without high-risk conditions and the known efficacy of the vaccine warrant its use," writes Neuzil.

Regarding the lack of vaccination coverage among some of the highest-risk patients, she adds that there are methods to increase vaccination coverage, including expanding access through nontraditional settings, such as pharmacies, workplaces, and school venues, the use of evidence-based practices such as reminder or recall notifications, and the use of immunization registries.

"One of the most consistent and relevant findings of operational research is that recommendation for vaccination from physicians and other healthcare professionals is a strong predictor of vaccine acceptance and receipt among patients," writes Neuzil.

Udell reports no conflicts of interest; disclosures for the coauthors are listed in the paper. Neuzil reports receiving grant funding from the Bill & Melinda Gates Foundation and Centers for Disease Control and Prevention.


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