Influenza and pneumonia, though rare, occurred at roughly the same rate in both the high-dose and standard-dose vaccine groups.
High-dose trivalent influenza vaccine did not significantly reduce all-cause mortality or cardiac- or pulmonary-related hospitalizations in patients with high-risk cardiovascular disease compared to the standard-dose quadrivalent vaccine, according to a paper published in JAMA. However, influenza vaccination remains strongly recommended for this population.
Investigators from the United States and Canada conducted a randomized clinical trial of more than 5,000 patients throughout 3 influenza seasons in order to determine if either of the vaccines would reduce all-cause mortality or cardiopulmonary hospitalizations in these patients. All of the patients involved had a recent acute myocardial infarction or heart failure hospitalization, plus at least 1 additional risk factor.
“This trial was predicated on the concept that reducing influenza in a high-risk population would lead to reduction in cardiovascular and pulmonary hospitalizations and deaths,” the study authors explained. “High-dose trivalent influenza vaccine, compared with standard-dose trivalent vaccine, had previously reduced laboratory-confirmed influenza, hospitalizations, and serious cardiopulmonary events in medically stable older adults in a large randomized trial.”
The patients were vaccinated for up to 3 influenza seasons between September 2016 and January 2019 around the U.S. and Canada, the study authors said. The participants were randomly assigned to receive a high-dose trivalent vaccine (2,630) or a standard-dose quadrivalent (2,630) vaccine.
Across the 3 influenza seasons, there were 7,154 total vaccinations and 99 percent of the patients completed the trial, the study authors said.
In the high-dose trivalent vaccine group, for 884 patients during the study period, there were 975 primary outcome events, the study authors found, including 883 hospitalizations for cardiovascular or pulmonary causes and 92 deaths from any cause.
They said that in the standard-dose quadrivalent vaccine group, there were 924 primary outcomes (including 846 cardiopulmonary hospitalizations and 78 deaths from any cause) for 837 patients for the study period.
The study authors also noted there were no significant differences observed between treatment groups for the secondary outcomes, related to cardiovascular death or hospitalization in each vaccination season or across all 3 seasons.
Influenza or pneumonia occurred rarely in both treatment groups, the investigators learned, with 10 influenza cases in the high-dose group and 8 in the standard dose group and 47 cases of pneumonia in the high-dose group and 41 cases in the standard-dose group.
The most frequent vaccine-related adverse events were injection site pain, myalgia, and swelling, but the study authors noted the vaccine was generally well-tolerated. These vaccine-related adverse events were more common in the high-dose group, they said. Severe vaccine-related reactions were self-reported by 55 patients (11 in the high-dose group and 44 in the standard-dose group). The study authors said 6 serious adverse events were reported, of which 2 were from the high-dose group and 4 were from the standard-dose group.
“Although this comparative effectiveness trial did not find a significant difference between the 2 vaccine formulations for the end points studied in a high-risk population, the incidence of hospitalization due to influenza was low in both vaccinated groups, and the benefit of either vaccine may be far greater than the incremental benefit of high-dose over standard-dose vaccines for influenza outcomes,” the study authors concluded. “Although these data do not refute the greater efficacy of high-dose vs. standard dose vaccines at reducing influenza among older adults, for the purposes of reducing death or cardiopulmonary hospitalizations in a high-risk cardiovascular population, the high-dose vaccine was not more effective than the standard-dose vaccine.”