A team, led by Orly Vardeny, PharmD, MS, Department of Medicine, University of Minnesota, Minneapolis VA Health Care System, evaluated whether high-dose trivalent influenza vaccine compared with standard-dose quadrivalent influenza vaccines could reduce all-cause death or cardiopulmonary hospitalization in high-risk patients with cardiovascular disease.
The flu has been temporally linked to cardiopulmonary morbidity and mortality among individuals with cardiovascular disease who may mount a less vigorous immune response to vaccination. Higher vaccines doses have been associated with reduced risk of influenza.
In the pragmatic multicenter, double-blind, active comparator randomized clinical trial, the investigators examined 5260 patients vaccinated for up to 3 influenza seasons in 157 sites in the US and Canada between September 21, 2016 and January 31, 2019.
Eligible patients included individuals with a recent acute myocardial infarction or heart failure hospitalization and at least 1 additional risk factor.
Each patient was randomly assigned to receive either high-dose trivalent (n = 2630) or standard-dose quadrivalent (n = 2630) inactivated influenza vaccine. The mean age of the patient population was 65.5 years old, with 72% of the study being male.
A total of 3289 participants (63%) had heart failure over 3 influenza seasons, with 7154 total vaccinations administered and 5226 participants (99.4%) completing the trial.
The researchers sought primary outcomes of the time to the composite of all-cause death or cardiopulmonary hospitalization during each enrolling season up to July 31, 2019. They also assessed vaccine-related adverse events.
For the high-dose arm of the study, there were 975 primary outcome events (883 hospitalizations for cardiovascular or pulmonary causes and 92 deaths from any cause) from the 884 patients during 3577 participant-seasons (event rate, 45 per 100 patient-years).
In the other group, there were 924 primary outcome events (846 hospitalizations for cardiovascular or pulmonary causes and 78 deaths from any cause) among 837 participants during 3577 participant-seasons (event rate, 42 per 100 patient-years) (HR, 1.06; 95% CI, 0.97-1.17; P = 0.21).
Vaccine-related adverse reactions occurred in 1449 individuals (40.5%) in the high dose group, compared to 1229 participants (34.4%) in the standard-dose group. For severe adverse reactions, there were 55 (2.1%) in the high-dose group and 44 (1.7%) in the standard-dose group.
“In patients with high-risk cardiovascular disease, high-dose trivalent inactivated influenza vaccine, compared with standard-dose quadrivalent inactivated influenza vaccine, did not significantly reduce all-cause mortality or cardiopulmonary hospitalizations,” the authors wrote. “Influenza vaccination remains strongly recommended in this population.”
Influenza can lead to significant morbidity and mortality, while increasing the burden in the health care system, particularly for individuals with underlying cardiovascular disease who are more susceptible to influenza-related complications and adverse clinical outcomes.
In previous observational studies, investigators have found a temporal association between influenza and cardiac events, including myocardial infarction and acute heart failure.
In addition, meta-analysis of randomized clinical trials show influenza vaccination is associated with a lower risk of major adverse cardiovascular events when compared to no vaccination.
The study, “Effect of High-Dose Trivalent vs Standard-Dose Quadrivalent Influenza Vaccine on Mortality or Cardiopulmonary Hospitalization in Patients With High-risk Cardiovascular Disease,” was published online in JAMA.