No difference in the primary outcome was observed between those randomized to influenza vaccine compared to placebo.
New findings suggest patients who received the influenza vaccine had no significant reduction in rates of major cardiovascular events on a year-round basis during a 3-year follow-up period, missing the primary study endpoint.
However, it was noted that patients with heart failure who received an annual vaccine had a lower rate of pneumonia and hospitalization on a year-round basis and a reduction in major cardiovascular events during peak flu season.
These findings were presented in a late-breaking session at The American College of Cardiology (ACC) 2022 Scientific Sessions in Washington, DC.
Previous reports have found a lower rate of cardiovascular events related to ischemia and death has been reported with influenza vaccination. Moreover, data show 80% of CV disease burden occurs in low, middle-income countries with low use of influenza vaccines.
Led by Mark Loeb, MD, McMaster University, the double-blind, randomized trial compared inactivated influenza vaccine to placebo in the prevention of CV outcomes in 10 countries in Asia, the Middle East, and Africa over 3 influenza seasons.
The eligibility included patients aged ≥18 years with a clinical diagnosis of heart failure and NYHA functional class II, III, and IV. The study vaccines consisted of a 0.5 mL IM dose of inactivated influenza vaccine or placebo (0.5 mL saline). It was administered annually for 3 seasons.
Within the study design, primary outcomes consisted of a composite of cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke, as well as the first co-primary and heart failure hospitalizations.
Secondary outcomes consisted of a component of primary outcomes, as well as hospitalizations for heart failure. The primary analysis were events (irrespective of influenza circulation) analyzed by intention-to-treat for the first and second primary composite outcomes.
A total of 5,129 participants were randomized to either influenza vaccine (n = 2560) or placebo (n = 2569), with a mean age of 57.2 years and 51.4% were female. Data show 95.7% of patients had NYHA Class II or III heart failure.
Over a median of 2.9 years, 380 first primary events (14.8%) occurred in the influenza vaccine group and 410 events (16.0%) occurred in the placebo group (hazard ratio [HR], 0.93; 95% CI, 0.81 - 1.07; P = .30).
Overall, investigators observed the composite primary outcome occurred in 691 participants, while 1,470 experienced the composite co-primary endpoint. On a yearly basis, no difference was seen in the rates of events in those who had received a flu vaccine versus those who had not. In other analyses, rates of pneumonia were 42% lower and hospitalizations were 15% lower among those who had received a flu shot.
Investigators additionally found a significant reduction in the first primary endpoint with flu vaccination, when the analysis was limited to periods of peak influenza circulation. However, when there was no low flu circulation, there were no significant differences in endpoints between groups.
In an accompanying press release, Loeb noted that further large-scale observational studies could help clarify the benefits of influenza vaccination.
“I think this study offers an important message about vaccines generally—that it is important to do randomized controlled trials in populations that historically haven’t had a very high uptake of vaccines,”Loeb stated. “These types of [research] gaps have to be filled."
The late-breaker, “Randomized Controlled Trial Of Influenza Vaccine In Patients With Heart Failure To Reduce Adverse Vascular Events,” was presented at ACC 2022.