Influenza vaccination to improve outcomes for patients with acute heart failure (PANDA II): a multiregional, seasonal, hospital-based, cluster-randomised, controlled trial in China.

Abstract

BACKGROUND: Influenza vaccination is widely recommended to prevent death and serious illness in vulnerable people, including those with heart failure. However, the randomised evidence to support this practice is limited and few people are vaccinated in many parts of the world. We aimed to determine whether influenza vaccination can improve the outcome of patients after an episode of acute heart failure requiring admission to hospital in China.

METHODS: We undertook a pragmatic, multiregional, parallel-group, cluster (hospital)-randomised, controlled, superiority trial over three winter seasons in China. Participating hospitals were located in the counties of 12 provinces with the capability of establishing a point-of-care service to provide free influenza vaccination to a sufficient number of patients before their discharge, if allocated to the intervention group. No such service was used in hospitals allocated to usual care (control) but patients were informed of fee-for-service influenza vaccination being available at local community medical centres, as per usual standard of care. Hospitals were randomised (1:1) in each year, stratified by province and up to three times (ie, new randomisation for each season), to include eligible adult (aged =18 years) patients with moderate to severe heart failure (New York Heart Association class III or IV) and no contraindication to influenza vaccination. Patient enrolment was conducted over three consecutive winter seasons, from October in each year to March of the following year, between 2021 and 2024. All patients received usual standard of care and were followed up at 1, 3, 6, and 12 months after their hospital discharge by trained study personnel using a standardised protocol. The primary outcome was a composite of all-cause mortality or any hospital readmission over 12 months, excluding events that occurred within 30 days after hospital discharge at all sites and in the summer season only for sites in northern China. The effect of the intervention was assessed at an individual level in the modified intention-to-treat population (all randomly assigned patients with available information until the time of last follow-up, excluding censored events) with a two-level hierarchical logistic regression model that included study period (year) as a fixed effect, and hospital and hospital-period as random effects, with the censored events excluded. The trial is registered at the Chinese Clinical Trial Registry (ChiCTR2100053264).

FINDINGS: Of 252 hospitals assessed for eligibility, 196 hospitals agreed to join and were randomised in three batches at the beginning of each winter season from October, 2021, but 32 hospitals subsequently withdrew before any patients were included. Overall, 7771 participants were enrolled at 164 hospitals in each winter season between Dec 3, 2021, and Feb 14, 2024, with 3570 assigned to the influenza vaccination group and 4201 to the usual care (control) group. The primary outcome occurred in 1378 (41·2%) of 3342 patients in the vaccination group and in 1843 (47·0%) of 3919 patients in the usual care group (odds ratio 0·83 [95% CI 0·72-0·97]; p=0·019). The result was consistent in the sensitivity analysis. The number of participants with a serious adverse event was significantly lower in the vaccination group (1809 [52·5%] of 3444) than the usual care group (2426 [59·0%] of 4110; odds ratio 0·82 [0·70-0·96]; p=0·013).

INTERPRETATION: Influenza vaccination during a hospital admission in patients with acute heart failure can improve their survival and reduce likelihood of readmission to hospital over the subsequent 12 months. The integration of influenza vaccination into inpatient care could offer a widely applicable strategy for an underserved high-risk patient group, that is relevant to resource-limited and possibly resource-rich settings.

FUNDING: Sanofi and the Chinese Society of Cardiology.