High-Dose Vaccine Does Not Mitigate Influenza-Associated Cardiopulmonary Risk

A high-dose trivalent influenza vaccine does not reduce cardiopulmonary event risk during the influenza season compared with the standard dose. These findings were published in JAMA Network Open.

Influenza infections have been associated with higher rates of myocardial infarction (MI) and heart failure (HF). To mitigate this associated risk, the INVESTED (Influenza Vaccine to Effectively Stop Cardio Thoracic Events and Decompensated Heart Failure; ClinicalTrials.gov Identifier: NCT02787044) trial investigated whether a high-dose influenza vaccine may lower cardiopulmonary event rates during influenza season.

The INVESTED study was a randomized, double-blind, active comparator trial conducted at 157 sites in the United States and Canada between 2016 and 2019. Patients (N=5260) with high-risk cardiovascular disease (CVD) who had been hospitalized in the past 12 months for MI or in the past 24 months for HF were randomly assigned to receive a high-dose trivalent (n=1548) or standard-dose quadrivalent (n=1546) influenza vaccine. In this secondary analysis of the INVESTED trial data, the primary outcome was to evaluate whether the high-dose vaccine was associated with decreased cardiopulmonary event risk.

The high- and standard-dose recipients had mean ages of 65 (SD, 13) and 67 (SD, 13) years, 74.4% and 74.8% were men, 73.0% and 71.8% were White, they had BMI of 31.9 (SD, 8.1) and 31.7 (SD, 7.7), and they had ejection fraction of 41% (SD, 17%) and 42% (SD, 16%), respectively.

When there was a 1% increase in influenza-like illness activity in the prior week, risk for the composite outcome of cardiopulmonary hospitalizations and all-cause mortality was increased (adjusted odds ratio [aOR], 1.14; 95% CI, 1.07-1.21; P <.001). Similarly, higher influenza-like illness activity associated with elevated risk for cardiopulmonary hospitalizations (aOR, 1.13; 95% CI, 1.06-1.21; P <.001) and cardiovascular hospitalizations (aOR, 1.12; 95% CI, 1.04-1.19; P =.001). Influenza activity was not significantly related to risk for pulmonary hospitalizations (aOR, 1.18; 95% CI, 0.99-1.40; P =.06) or all-cause mortality (aOR, 1.00; 95% CI, 0.88-1.13; P >.99).

Stratified by vaccine dose, the high-dose vaccine did not associate with decreased risk for the primary composite outcome relative to the standard dose (aOR, 1.07; 95% CI, 0.95-1.20; P =.25). Similarly, no trends were observed in months with typically high influenza activity (aOR, 1.09; 95% CI, 0.97-1.24; P =.15) or during weeks with high influenza-like illness activity (aOR, 0.88; 95% CI, 0.65-1.20; P =.43).

These findings may be limited, as patient-level influenza infection data were not collected in INVESTED.

 “…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,” the study authors wrote. “Other seasonal factors may also play a role in the higher rate of CV events associated with high rates of influenza.”

Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.