BOSTON — Higher dose influenza vaccines don’t appear to reduce risk of cardiopulmonary events during periods of increased, local flu activity, according to a recent study.
Researchers from Brigham and Women’s Hospital, Harvard Medical School and colleagues, including those from the VA Minneapolis Health Care System, advised that influenza-like illness (ILI) activity has been associated with increased risk of cardiopulmonary (CP) events during the influenza season.
A previous study, in the Influenza Vaccine to Effectively Stop Cardio Thoracic Events and Decompensated Heart Failure (INVESTED) trial, found that high-dose trivalent influenza vaccine was not superior to standard-dose quadrivalent vaccine for reducing these events in patients with high-risk cardiovascular (CV) disease.
The study published in JAMA Network Open sought to evaluate whether high-dose trivalent influenza vaccination is associated with benefit over standard-dose quadrivalent vaccination in reducing CP events during periods of high, local influenza activity.1
The effort was a prespecified secondary analysis of INVESTED, a multicenter, double-blind, active comparator randomized clinical trial conducted over three consecutive influenza seasons from September 2016 to July 2019. Follow-up ended in July 2019, and data were analyzed from Sept. 21, 2016, to July 31, 2019.
The study team ascertained weekly national Centers for Disease Control and Prevention (CDC)-reported, state-level ILI activity to assess the weekly odds of the primary outcome. The study population included 3,094 patients with high-risk CV disease from participating centers in the United States.
Participants were randomized to high-dose trivalent or standard-dose quadrivalent influenza vaccine and revaccinated for as many as three seasons. Defined as the primary outcome was the time to composite of all-cause death or CP hospitalization within each season. Researchers said that additional measures included weekly CDC-reported ILI activity data by state.
Participants had a mean age of 65 and were 75% male. Analyzed 129,285 person-weeks of enrollment, including 1,396 composite primary outcome events, which included 1,278 patients having CP hospitalization and 118 dying.
Results indicated that a 1% ILI increase in the prior week was associated with an increased risk in the primary outcome (odds ratio [OR], 1.14; 95% CI, 1.07-1.21; P < 0.001), CP hospitalization (OR, 1.13; 95% CI, 1.06-1.21; P < 0.001), and CV hospitalization (OR, 1.12; 95% CI, 1.04-1.19; P = 0.001), after adjusting for state, demographic characteristics, enrollment strata, and CV risk factors.
“Increased ILI activity was not associated with all-cause death (OR, 1.00; 95% CI, 0.88-1.13; P > 0.99),” the authors pointed out, adding, “High-dose compared with standard-dose vaccine did not significantly reduce the primary outcome, even when the analysis was restricted to weeks of high ILI activity (OR, 0.88; 95% CI, 0.65-1.20; P = 0.43). Traditionally, warmer months in the U.S. were associated with lower CV risk independent of local ILI activity.”
The researchers concluded that, based on their secondary analysis of a randomized clinical trial, ILI activity was temporally associated with increased CP events in patients with high-risk CV disease, and a higher influenza vaccine dose did not significantly reduce temporal CV risk. “Other seasonal factors may play a role in the coincident high rates of ILI and CV events,” they suggested.
- Hegde SM, Claggett BL, Udell JA, Kim K, Joseph J, Farkouh ME, Peikert A, Bhatt AS, Tattersall MC, Bhatt DL, Cooper LS, Solomon SD, Vardeny O. Temporal Association Among Influenza-Like Illness, Cardiovascular Events, and Vaccine Dose in Patients With High-Risk Cardiovascular Disease: Secondary Analysis of a Randomized Clinical Trial. JAMA Netw Open. 2023 Sep 5;6(9):e2331284. doi: 10.1001/jamanetworkopen.2023.31284. PMID: 37707817; PMCID: PMC10502520.