High-dose inactivated influenza vaccine did not reduce all-cause death or hospitalization for cardiopulmonary causes compared with a standard-dose vaccine in patients with high-risk cardiovascular disease (CVD), according to data presented by Orly Vardeny, PharmD, MS, of associate professor at University of Minnesota Medical School, at a news briefing at the American Heart Association Scientific Sessions 2020.
According to Dr. Vardeny, individuals with underlying CVD are more susceptible to influenza complications and adverse clinical outcomes. Observational studies have demonstrated a temporal association between influenza and acute cardiac events. In addition, a meta-analysis of randomized clinical trials showed that influenza vaccination was associated with lower risk of major adverse cardiovascular events compared with no vaccination.
The high-dose vaccine contains four times the amount of antigen and has been shown to reduce risk for laboratory symptomatic influenza compared with the standard dose. However, the Advisory Committee on Immunization Practices does not preferentially recommend one vaccine formulation over another.
Here, Dr. Vardeny and colleagues hypothesized that high-dose influenza vaccine would improve clinical outcomes in patients with CVD compared with standard dose.
The INVESTED trial enrolled individuals within 12 months of hospitalization of myocardial infarction or 24 months of hospitalization for heart failure plus one of a multitude of additional risk factors. The patients were randomly assigned to high-dose trivalent inactivated influenza vaccine (n=2,630) or standard-dose quadrivalent inactivated influenza vaccine (n=2,630). Patients could be revaccinated with their vaccine type for up to three influenza seasons. The primary endpoint was composite of death or cardiopulmonary hospitalization within each influenza season.
The study’s Data Monitoring Committee recommended early termination of the trial for futility. There were no significant difference between groups with regard to all-cause mortality or cardiopulmonary hospitalization (HR=1.06; 95% CI, 0.97 to 1.17; P=0.21). Results were consistent across prespecified secondary endpoints and subgroups. In general, the influenza vaccine as very well tolerated. Patients who received high-dose vaccine had a higher frequency of injection site pain or swelling as well as myalgias.
Dr. Vardeny said that it is important to place these results into context.
“We compared two active vaccine formulations in a very high-risk population and both of these are known to reduce influenza illness,” she said. “Thus receipt of any influenza vaccine in high-risk patients may be protective and limit potential benefit of high-dose vaccine in reducing cardiopulmonary events.
“Importantly these results do not detract from prior trials showing benefit of high-dose vaccine on reducing influenza illness nor do they minimize the importance of influenza vaccine in patients with high-risk cardiovascular disease for whom influenza vaccination remains strongly recommended,” Dr. Vardeny concluded.