The superior performance of high-dose quadrivalent influenza vaccines (QIV-HD) over standard-dose quadrivalent vaccines (QIV-SD) is consistent whether or not a patient has chronic kidney disease (CKD), according to a secondary analysis of the DANFLU-1 trial presented at ESC 2024 and simultaneously published in JACC.

The pragmatic, open-label DANFLU-1 feasibility trial, conducted during the 2021-2022 influenza season, randomized 12,477 Danish citizens aged 65-79 years to receive either a QIV-HD or QIV-SD vaccine and examined time to first and recurrent events, including hospitalization for influenza or pneumonia, cardiorespiratory disease, cardiovascular disease and COVID-19, as well as all-cause hospitalization and all-cause mortality. Follow-up for clinical outcomes was the time from 14 days after vaccination through May 31, 2022.

Among the study patients, 2,462 (19.7%) had chronic kidney disease (mean age 73.0 years; 44.5% women), defined as an estimated glomerular filtration rate of <60 mL/min/1.73 m2 on at least two occasions more than three months apart, a urine albumin-creatinine ratio >30 mg/g or a urine albumin >20 mg/L. None of the patients were on dialysis.

Results from the main results of DANFLU-1 showed that 38 participants were hospitalized with influenza or pneumonia. This secondary analysis showed that having CKD did not modify the effect of the QIV-HD or QIV-SD vaccine on first or recurrent events. Of the participants with CKD, three patients (3.9%) who received the QIV-HD vaccine were hospitalized compared with 12 (16.6%) in the QIV-SD group (hazard ratio [HR], 0.24; 95% CI, 0.07-0.84; pint<0.43).

Findings showed in the overall cohort fewer hospitalizations for influenza or pneumonia with QIV-HD (2.6% vs. 7.5%; HR, 0.36; 95% CI, 0.17-0.73; pint<0.43). Overall, there were 10 hospitalizations for pneumonia or influenza among patients in the QIV-HD arm and 33 in the QIV-SD arm (3.3% vs. 10.9%; HR, 0.30; 95% CI, 0.14-0.64; pint<0.27).

Furthermore, the incidence rate ratio with the QIV-HD vaccine among patients with CKD was 0.16 for recurrent hospitalization for influenza or pneumonia, 0.56 for cardiorespiratory disease and 0.77 for all-cause hospitalization. Of note, neither vaccine impacted cardiovascular outcomes, with a similar rate of cardiovascular hospitalization (21.9% of patients with QIV-HD and 21.4% of patients with QIV-SD).

Katja Vu Bartholdy, MD, and colleagues write their finding suggest "the superior performance of QIV-HD compared to QIV-SD on important clinical outcomes is consistent across CKD status." They also note a number of study limitations, including the DANFLU-1 trial not being powered for this analysis and the lack of correction for multiple associations, and the generalizability because of possible differences in circulating virus strains and population demographics in other countries.