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Results of the INVESTED trial offer clinicians into the effects of high-dose versus standard-dose influenza vaccines in patients with high-risk cardiovascular disease.
A timely new study is comparing the effects of high-dose and standard-dose flu vaccines in patients with high-risk cardiovascular disease.
A randomized clinical trial with more than 5000 patients, results of the study suggest the high-dose trivalent influenza vaccine did not significantly reduce all-cause mortality or hospitalizations for cardiac or pulmonary causes compared to the standard-dose quadrivalent vaccine in patients with a recent myocardial infarction or hospitalization for heart failure.
Originally presented at the American Heart Association 2020 Scientific Sessions, the INVESTED trial was designed by investigators at Brigham and Women’s Hospital and the University of Wisconsin-Madison as a pragmatic, randomized, double-blind, active comparator trial conducted at 157 centers in the US and Canada over 3 influenza seasons.
Investigators considered patients eligible for the study if they were hospitalized for acute myocardial infarction in the past 12 months or for heart failure in the past 24 months and at least 1 of the following additional risk factors: older than 65 years, current or prior left ventricular ejection fraction (LVEF) less than 40%, diabetes, BMI of 30 or greater, history of chronic kidney disease, ischemic stroke, peripheral artery disease, current tobacco use, or a myocardial infarction or heart failure hospitalization prior to the index hospitalization.
In total, investigators randomized a cohort of 5260 patients in the study. This cohort had a mean age of 65.5 (SD, 12.6) years, 72% were men, 63% had a history of heart failure, and received 7154 total vaccinations over the 3 influenza seasons included in the study.
Of the 5260 randomized in the study, 2360 were randomized to receive the standard-dose vaccine and 2630 were randomized to receive the high-dose vaccine. Of note, patients were excluded based on known allergy or hypersensitivity to influenza vaccines, severe allergy to egg protein, a life expectancy less than 9 months, or if they were pregnant or lactating.
The primary outcome of the study was the time to a composite endpoint of all-cause death or cardiopulmonary hospitalization. Investigators also collected data related to vaccine-related adverse events as part of their analyses.
At the end of the study, 5226 (99.4%) of participants completed the trial. Among those in the high-dose group, investigators observed a total of 975 primary outcome events among 884 participants during 3577 participants-seasons—yielding an event rate of 45 per 100 patients-years. Among those in the standard-dose group, investigators observed 924 primary outcome events among 837 participants during 3577 participants-seasons—yielding an event rate of 42 per 100 patients-years (HR, 1.06; 95% CI, 0.97-1.17; P=.21).
Of note, investigators pointed out the 975 primary outcome events in the high-dose group were 883 hospitalizations for cardiovascular or pulmonary issues and 92 deaths from any cause. Among the 924 events in the standard-dose group, 846 were hospitalizations for cardiovascular or pulmonary issues and 78 deaths from any cause. When evaluating vaccine-related adverse events, investigators found events occurred in 1449 (40.5%) of the high-dose group compared to 1229 (34.4%) in the standard-dose group. Further analysis indicated severe adverse reactions occurred in 55 (2.1%) high-dose patients and 44 (1.7%) standard-dose participants.
In an editorial comment published in JAMA, a pair of physicians from the National Center for Immunization and Respiratory Diseases at Centers for Disease Control and Prevention detailed the difficulty of managing influenza risk among patients with cardiovascular disease.
“With an aging global population and increasing numbers of people with cardiac diseases, improved prevention efforts to reduce influenza-associated CVD outcomes are overdue. Persons with cardiovascular conditions are at increased risk of influenza virus infection and associated complications due to immunosenescence and, possibly, “inflamm-aging” (ie, a chronic low-level state of inflammation suspected to impair immune responses). However, vaccines are also known to be less effective in these populations and in older adults due to blunted humoral immune responses, and current influenza vaccines are known to have suboptimal effectiveness,” wrote editorial authors.
This study, “Effect of High-Dose Trivalent vs Standard-Dose Quadrivalent Influenza Vaccine on Mortality or Cardiopulmonary Hospitalization in Patients With High-risk Cardiovascular Disease,” was published in JAMA.