High-dose influenza vaccine is not more effective than standard-dose influenza vaccine in reducing the risk of dying or being hospitalized for cardiovascular causes in high risk adults, a study has found.

Patients with underlying cardiovascular disease are more susceptible to influenza-related complications and adverse clinical outcomes. The INVESTED trial tested the hypothesis that high-dose flu vaccine would improve clinical outcomes in patients with high-risk cardiovascular disease compared to standard-dose flu vaccine.

The randomized, double-blind, active-controlled trial enrolled 5,260 men and women (mean age, 66 years) with recent heart attack or hospital stay for heart failure and at least one additional risk factor.

Half received a high-dose trivalent influenza vaccine and half received a standard-dose, quadrivalent vaccine. Participants could remain in the study for up to three influenza seasons and receive the same vaccine each year.

The primary outcome was death or hospitalization for cardiopulmonary events. The trial was halted early for futility after 1,770 primary outcome events, lead researcher Dr. Orly Vardeny said in a presentation of the results at a press briefing November 17 at the American Heart Association (AHA) virtual annual meeting.

There was no significant difference in deaths or hospitalizations for cardiac or pulmonary causes between the high-dose and standard-dose vaccine formulations (44.5 vs. 41.9 events per 100 patient years, respectively), with a hazard ratio of 1.06 (P=0.21), reported Dr. Vardeny of the University of Minnesota Medical School, in Minneapolis. The results were consistent across 12 prespecified subgroups.

There were no significant between-group differences in any secondary outcome or hospital admission for influenza or pneumonia. In general, both influenza vaccines were well tolerated, although injection site pain and swelling were more common with the high-dose vaccine.

Dr. Vardeny said it's important to place these results into context. "We compared two vaccine formulations in a very-high-risk population. Both vaccines are known to reduce influenza illness. Thus, the receipt of any influenza vaccine may have been protective and limit the potential additional benefit of the high-dose vaccine in reducing cardiopulmonary events," she told the briefing.

Importantly, she added, "These results do not detract from previous trials showing the benefit of high-dose vaccine on reducing influenza illness, nor do they minimize the importance of flu vaccination in patients with high-risk cardiovascular disease for whom influenza vaccination remains strongly recommended. For an older individual, it may still be worth getting the high-dose vaccine to prevent flu."

Offering outside perspective at the briefing, Dr. Harriette Van Spall of McMaster University, in Hamilton, Canada, noted that the trial "might not have found a difference because no difference might exist. It is possible that there is no additional effect of the high-dose vaccine, particularly on the clinical endpoints chosen."

Briefing moderator Dr. Manesh Patel of Duke University School of Medicine, in Durham, North Carolina, said, "Certainly, there is always a possibility that no difference exists. It's always difficult to demonstrate a finding against an active comparator. Getting the flu vaccine may be the first most important step in itself."

Funding for the study was provided by the National Heart, Lung, and Blood Institute. Additional funding and vaccine were provided by Sanofi-Pasteur who were not involved in the design, conduct or interpretation of the trial results. Dr. Vardeny has received consulting fees from Sanofi-Pasteur.

SOURCE: https://bit.ly/35STmoF American Heart Association (AHA) 2020 Scientific Sessions, presented November 17, 2020.