DANFLU-1: High-dose quadrivalent flu vax reduces hospitalization, death in older adults

Older adults who receive a high-dose quadrivalent influenza vaccine have a 49 percent reduced risk of death and a 64 percent reduced risk of hospitalization for influenza or pneumonia compared with those who receive a standard-dose vaccine, results of the DANFLU-1 study showed.

The open-label trial was conducted in Denmark during the 2021/2022 northern hemisphere influenza season. The 12,477 participants aged 65–79 years (mean age 71.7 years, 47.1 percent female) were randomized 1:1 to receive either a high-dose (n=6,245) or standard-dose (n=6,232) quadrivalent influenza vaccine. They were followed up using nationwide administrative healthcare registries from 14 days post-vaccination to May 31, 2022. The baseline characteristics were comparable between the study participants and individuals of the same age group in the general Danish population.

About 20 percent of the participants had chronic cardiovascular disease. The most common comorbidities were hypertension (52 percent), cancer (11 percent), and diabetes (9 percent).

The incidence of hospitalization for influenza or pneumonia was significantly reduced among individuals who received the high-dose vs standard-dose influenza vaccine (0.2 percent vs 0.4 percent; relative risk reduction [rVE], 64.4 percent, 95 percent confidence interval [CI], 24.4–84.6 percent). [ESC 2022, Hot Line Session 2]

The incidence of all-cause mortality was also significantly reduced in high-dose vs standard-dose influenza vaccine recipients (0.3 percent vs 0.7 percent; rVE, 48.9 percent, 95 percent CI, 11.5–71.3 percent).

Participants who received the high-dose vs standard-dose influenza vaccine also had a reduced incidence of hospitalization for respiratory disease (rVE, 40.1 percent, 95 percent CI, -1.8 to 65.5 percent), hospitalization for cardio-respiratory disease (rVE, 12.1 percent, 95 percent CI, -15.5 to 33.3 percent), and any-cause hospitalization (rVE, 6.9 percent, 95 percent CI, -5.2 to 17.6 percent).

Serious adverse event (SAE) rates did not significantly differ between high-dose and standard-dose vaccine recipients (6.0 percent vs 6.5 percent; p=0.22), nor did rates of cardiovascular SAEs (1.0 percent vs 1.4 percent; p=0.047), respiratory SAEs (0.4 percent each), gastrointestinal SAEs (0.4 percent each), infection-related SAEs (0.4 percent vs 0.3 percent; p=0.65), or injury-related SAEs (1.5 percent vs 1.6 percent; p=0.75). Fatal SAEs occurred in a comparable proportion of high-dose and standard-dose vaccine recipients (0.1 percent vs 0.2 percent [n=8 vs 13]; p=0.27). One high-dose and four standard-dose vaccine recipients experienced serious adverse reactions. 

“High-dose vaccines are approved for adults aged ≥65 years in most countries, and for those ≥60 years in some countries,” said senior author and chief investigator Professor Tor Biering-Sørensen from the Centre for Translational Cardiology and Pragmatic Randomised Trials, University of Copenhagen, Copenhagen, Denmark.

“However, only a few countries offer older adults a high-dose vaccine by default. Thus, high-dose vaccines are not widely implemented despite accumulating evidence of additional protection against influenza infection and influenza-related morbidity compared with standard-dose vaccines.”

“[The DANFLU-1 trial] hinted at benefits in morbidity and mortality with a high-dose compared with a standard-dose [flu vaccine],” he noted. “The reductions in hospitalizations and all-cause mortality with the high-dose vaccine were encouraging but require confirmation in a larger trial before potentially guiding clinical practice.”

The trial also demonstrated the feasibility of integrating a randomized influenza vaccine trial into the routine Danish vaccination programme as well as the use of administrative health registries for data collection, said Biering-Sørensen. The single study visit and the use of health registries for data ascertainment reduced the burden on participants and study investigators, he said.