Key Points:
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- Prior observational and small randomized studies suggested that influenza vaccine may reduce future cardiovascular events in patients with known coronary artery disease.
- The Influenza vaccination After Myocardial Infarction (IAMI) study is a double-blind, randomized controlled trial that tested whether influenza vaccination early after admission with myocardial infarction or high-risk coronary artery disease reduces cardiovascular events.
- Late-breaking research presented in a Hot Line session today at ESC Congress 2021 showed that influenza vaccination reduces the risk of all-cause death, myocardial infarction, or stent thrombosis at 12 months in hospitalized patients with cardiovascular disease.
- According to study authors, these findings suggest that influenza vaccination is underutilized in the cardiovascular disease population and should be considered as part of in-hospital treatment after myocardial infarction.
Adults with cardiovascular disease are at higher risk of complications from influenza compared to the rest of the population. Correspondingly, more patients die from cardiovascular causes during influenza epidemics than during non-epidemic periods, in part due to myriad deleterious effects of the virus on the inflammatory milieu in already diseased coronary vessels. Prior data has supported an observational protective effect from influenza vaccination on cardiovascular events, but no large clinical trial has explored whether influenza vaccination could prevent cardiovascular events in patients with known heart disease. Currently, influenza vaccination is recommended for patients with cardiovascular disease after an acute myocardial infarction (MI) but is not incorporated into the standard of care. In fact, influenza vaccination carries a class I, level of Evidence B recommendation in both AHA/ACC and ESC secondary prevention guidelines. Unfortunately, uptake of these recommendations is low and vaccination timing undecided. The Influenza vaccination After Myocardial Infarction (IAMI) study therefore sought to determine whether influenza vaccination improves clinical outcomes in patients with recent myocardial infarction or high-risk coronary disease.
IAMI was a randomized, double-blind, placebo-controlled, investigator-initiated trial designed to evaluate efficacy of influenza vaccine following MI (99.7% of patients) or percutaneous coronary intervention (PCI) in high-risk patients with coronary artery disease. The trial was conducted at 30 centers in 8 countries over 4 influenza seasons from October 2016 through end of February 2020. Participants were enrolled during the northern hemisphere influenza season from September through February, and from May through September in the southern hemisphere influenza season (Bangladesh and Australia). Influenza vaccine content was consistent with WHO recommendations according to season and hemisphere. The primary endpoint was the composite of all-cause death, MI, or stent thrombosis at 12 months. A hierarchical testing strategy was used for the key secondary endpoints: all-cause death, cardiovascular death, MI, and stent thrombosis.
Unfortunately, the study was met with several challenges including slow recruitment and need to halt the trial on April 7, 2020 prior to attaining the prespecified sample size as a result of the COVID-19 pandemic. Nonetheless, 2571 participants (58% of target) were randomized to influenza vaccine or placebo. The results of this study are published today in Circulation .
Results announced today as a ESC Congress 2021 Hot Line study showed that the baseline characteristics of the participants were well- balanced between the trial groups. The average age of participants was 60 years and 18% were women. Over the 12-month follow-up, the primary outcome occurred in 67 participants (5.3%) who received the influenza vaccine and 91 participants (7.2%) assigned to the placebo group (hazard ratio, 0.72; 95% confidence interval, 0.52 to 0.99; P=0.040). Amongst secondary endpoints, rates of all-cause death were 2.9% and 4.9% (hazard ratio, 0.59; 0.39 to 0.89; P=0.010), of cardiovascular death 2.7% and 4.5%, (hazard ratio, 0.59; 0.39 to 0.90; P=0.014), and of MI 2.0% and 2.4% (hazard ratio, 0.86; 0.50 to 1.46, P=0.57) in the influenza vaccine and placebo groups, respectively. Notably findings were consistent with the primary composite endgroup results across all prespecified subgroups and in all countries. The authors point out that time-to-event-curves begin to separate almost immediately after injection, suggesting that the influenza vaccination may provide a therapeutic effect during the vulnerable and highly inflammatory post-MI period.
Serious adverse events were rare and of similar type and incidence in the placebo and influenza vaccine groups. Injection site reactions such as pain, redness, swelling, and hardening were reported significantly more often in patients assigned to influenza vaccine. These findings confirm previously established data that influenza vaccine can be safely administered after a cardiovascular event.
In their manuscript the authors conclude that, “among participants with MI or high-risk coronary heart disease, influenza vaccine administered within 72 hours of an invasive coronary procedure or hospitalization resulted in a lower risk at 12 months of a composite primary outcome of all-cause death, MI, or stent thrombosis, as well as a lower risk of all-cause death and of cardiovascular death compared with placebo.” Principal investigator Professor Ole Fröbert of Örebro University, Sweden noted that “Our findings suggest that influenza vaccination should be considered as part of in-hospital treatment after myocardial infarction.”