Limitations
infection
EVENTS, SECONDARY, INFECTION, INFLUENZA
Several limitations of this analysis should be noted. Inferences about the association between patient-level influenza illness or other respiratory viruses and subsequent events could not be made, as the respiratory influenza infection status of participants was not assessed in this study. State-level ILI activity may not have represented regional-level or patient-level ILI activity. Only states with available ILI activity were included in this analysis, which limited generalizability to participants, excluding those in Florida and Canada. That we did not randomize patients to placebo prevented us from drawing conclusions about the impact of any influenza vaccination on the temporal association between ILI activity and CV events. Also, the difference in valence between the high-dose trivalent influenza vaccine and the standard-dose quadrivalent vaccine may have contributed to the absence of outcome modification of the vaccine dose, with the standard-dose vaccine providing additional coverage for the influenza B/Yamagata strain. Changes in seasonal temperature, humidity, weather patterns, and other environmental factors were not accounted for in this analysis. Additionally, the trial had limited power for this prespecified secondary analysis.