A high-dose influenza vaccine was no more effective than the standard-dose vaccine at reducing the risk of severe outcomes among patients with heart disease, NIH study finds.
A high-dose trivalent influenza vaccine was no more effective than the standard dose quadrivalent vaccine at reducing the risk of death or hospitalization for heart or pulmonary-related causes among patients with heart disease, according to a news release from the National Institutes of Health.
The findings, from the NIH-funded Influenza Vaccine to Effectively Stop Cardio Thoracic Events and Decompensated heart failure (INVESTED) trial, were published online December 4th in the Journal of the American Medical Association and had been previewed in mid-November at the 2020 virtual American Heart Association Scientific Sessions.
Individuals with heart disease are at increased risk for complications from infection with influenza including myocardial infarction (MI), hospitalization for heart failure, and death. Strong recommendations are in place for annual vaccination against flu for this high-risk population and, according to the NIH release, at least one study has suggested that a high-dose vaccine might more effectively reduce this risk than the standard-dose vaccine.
The high-dose vaccine is currently approved in the United States for people aged ≥65 years and has been shown to reduce the incidence of influenza infection in these patients.
To determine if there is a benefit in the higher dose, INVESTED researchers conducted a randomized double-blind trial that was conducted at 157 sites in the US and Canada over 3 influenza seasons. Launched in September 2016, the trial enrolled 5,260 patients. Eligible participants had been hospitalized for a cardiovascular (CV) event, including MI, within the previous year or for heart failure within the previous 2 years. Each participant also had at least one additional risk factor for CV disease, eg, age >65 years, current smoking, renal disease, peripheral arterial disease, or a history of stroke.
Participants were randomized to receive the high-dose trivalent or standard dose quadrivalent vaccine and could remain in the study for up to 3 years, between the 2016 and 2019 flu seasons; they received the same type of vaccine each year.
At the end of the study, the composite total of hospitalizations and deaths was roughly equal for both flu vaccine groups.
The authors offered several possible explanations for the findings. “First, we enrolled people at high risk for heart and lung-related hospitalizations,” said Orly Vardeny, PharmD, MS, lead study researcher and associate professor of medicine at the University of Minnesota’s Medical School and College of Pharmacy, Minneapolis, in the NIH statement, "so it’s possible that the incremental benefit of one vaccine over the other would not have overcome the high underlying risk in this population.”
Vardeny also noted that although there were many hospitalizations during the trial, only a small number were found to be caused by flu, raising the possibility that since all participants received the influenza vaccine, both the high- and low-dose formulas similarly reduced their risk for heart and lung hospitalizations.
“It’s important to remember that all participants in INVESTED received a vaccination, and that both vaccine formulations were generally well tolerated with very few patients experiencing severe adverse reactions, with no difference between groups,” said Scott Solomon, MD, study co-leader and professor of medicine at Harvard Medical School.
Neither group experienced meaningful vaccine-related side effects although participants in the high-dose group tended to have more typical injection-related side effects, such as pain, swelling, and muscle aches.
The study had several limitations including a focus on patients at high-risk for CV disease, use of vaccine formulations available during the 2016-17, 2017-18, and 2018-19 influenza seasons, and use of vaccines that were prepared in chicken eggs.
Future research, the study authors said, should examine whether other types of flu vaccine may be more protective for patients with high-risk conditions or whether a high-dose vaccine benefits low-risk cardiac patients more.
