Fact checked byRichard Smith

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September 14, 2023
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Flu season ups CV risk, not reduced by higher-dose vaccine in already high-risk patients

Fact checked byRichard Smith
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Key takeaways:

  • Increased CV risk was observed immediately following periods of heightened influenza spread.
  • Influenza vaccine dose size did not significantly impact risk for cardiopulmonary hospitalization or all-cause death.

Local influenza spread was associated with temporary increased CV risk, but flu vaccine dose — high or standard — did not prevent hospitalization for cardiopulmonary events or all-cause death in high-risk patients, researchers reported.

A secondary analysis of the INVESTED trial was published in JAMA Network Open.

flu shot
Increased CV risk was observed immediately following periods of heightened influenza spread.
Image: Adobe Stock

“Seasonal outbreaks of influenza occur primarily in winter months when transmission may be more favorable, and CV events demonstrate a similar temporal pattern. ... Influenza vaccine may be involved in reducing adverse CV outcomes, as suggested by observational and randomized clinical trials,” Sheila M. Hegde, MD, MPH, cardiovascular medicine specialist at Brigham and Women’s Hospital and instructor in medicine at Harvard Medical School, and colleagues wrote. “Whether treatment efficacy may be different during periods of high influenza-like illness (ILI) activity is not known.”

For the INVESTED trial, researchers enrolled 5,260 patients with MI in the prior year or HF hospitalization in the prior 2 years and at least one other risk factor to compare the clinical benefit of high- vs. standard-dose influenza vaccination on mortality and CV outcomes. Participants were randomly assigned to an annual high-dose trivalent inactivated influenza vaccine or a standard-dose quadrivalent inactivated influenza vaccine for three influenza seasons.

As Healio previously reported, in the main results of INVESTED, the high-dose influenza vaccine did not affect all-cause death, cardiac or pulmonary hospitalization compared with the standard-dose influenza vaccine in patients with a prior MI or HF hospitalization.

For the present analysis, researchers evaluated whether the high-dose influenza vaccine had any impact on cardiopulmonary events, CV events and all-cause death during periods of high, local influenza activity compared with standard dose.

The present study included 3,094 INVESTED participants (mean age, 65 years; 75% men) and the researchers used weekly CDC-reported, state-level ILI activity to assess the weekly odds of the primary outcome.

After adjusting for state, demographic characteristics, enrollment strata and CV risk factors, Hegde and colleagues observed that a 1% increase in ILI activity the prior week was associated with an increased risk for cardiopulmonary hospitalization (OR = 1.13; 95% CI, 1.06-1.21; P < .001) and CV hospitalization (OR = 1.12; 95% CI, 1.04-1.19; P = .001) but not all-cause death (OR = 1; 95% CI, 0.88-1.13; P > .99).

Influenza vaccine dose — high or standard — had no significant impact on the primary outcome, even when data were restricted to weeks of high ILI activity (OR = 0.88; 95% CI, 0.65-1.2; P = .43), according to the study.

“Influenza activity was temporally associated with an increasing risk of cardiopulmonary events, yet a higher-dose influenza vaccine did not significantly reduce temporal CV risk. Other seasonal factors may also play a role in the higher rate of CV events associated with high rates of influenza,” the researchers wrote. “Further studies and additional measures are needed to understand additional factors influencing the temporal association between influenza and CV events and to assess new strategies to reduce events.”