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Clinical outcomes were better for patients with recent myocardial infarction (MI) or high-risk coronary disease who got an influenza vaccination while they were in the hospital, the IAMI trial showed.

Combined rates of death, MI, and stent thrombosis at 12 months were significantly reduced for these high-risk patients who had been randomized to a flu vaccine as opposed to saline placebo (5.3% vs 7.2%, HR 0.72, 95% CI 0.52-0.99), reported Ole Fröbert, MD, PhD, of Örebro County, Sweden, during a Hot Line session at the .

There were 40% reductions in all-cause death and cardiovascular death in particular. MI was shown to be similarly frequent between groups, according to the IAMI report, which was simultaneously published online in .

"Patients with cardiovascular disease [CVD] should get their yearly flu shot," Fröbert urged during an ESC press conference. "If you give the influenza vaccine as part of routine care after MI, you will ensure high compliance."

CDC recommends an annual flu shot for people starting as young as 6 months. Vaccination carries a in both the American and European cardiology guidelines.

The issue is that many people don't follow the recommendation.

The vaccine should be offered to people with cardiovascular conditions "whenever there is opportunity to do so," commented Orly Vardeny, PharmD, MS, of the University of Minnesota and the Minneapolis VA Center for Care Delivery and Outcomes Research. "Whether in outpatient clinics or prior to discharge from a hospitalization, research shows that patients are more likely to get vaccinated when the vaccine is recommended by a healthcare provider."

Notably, Fröbert's group had targeted a sample of 4,400 people. However, the study suffered from slow recruitment and was prematurely terminated in April 2020 due to COVID-19 after enrolling just 58% of the intended number of participants.

A exploratory meta-analysis nevertheless bolstered the case that flu shots protect against cardiovascular death (HR 0.51, 95% CI 0.36-0.71) when IAMI was pooled with three other studies, Fröbert reported.

"Remember that influenza and CVD are two of the most common causes of hospitalizations and deaths worldwide," said ESC session discussant Barbara Casadei, MD, DPhil, of John Radcliffe Hospital in Oxford, England. She added that the flu and heart disease share a "reciprocal relationship" -- the presence of one increasing the risk of the other.

Although influenza vaccines show only 40-60% efficacy against flu illness (depending on the year), they do decrease all-cause deaths, according to Casadei, who also cited research showing these vaccines to be associated with lower rates of cardiovascular events among people with CVD -- especially those who had had an event the previous year.

was a double-blind trial conducted over four flu seasons in 2016-2020. Thirty participating hospitals (across eight countries in both the Northern and Southern hemispheres) randomized 2,571 hospitalized adults to influenza vaccination or saline placebo within 72 hours after an invasive procedure (i.e., coronary angiography or percutaneous coronary intervention) or after admission.

People were not eligible if they had already received their season's flu vaccine or said they planned on doing so.

Mean age was 60 years, and men accounted for over 80% of the cohort. Approximately 54% of people had presented with ST-elevation MI (STEMI), 45% non-ST elevation myocardial infarction (NSTEMI), and the remaining fewer than 1% with stable coronary artery disease.

The vaccine and placebo groups shared similarly low rates of serious adverse events over the course of the study.

Casadei urged caution in interpreting the study results as early study termination significantly reduced the statistical power.

ESC panelists dedicated much of their discussion on how flu vaccines can protect against cardiovascular death when the data do not show a significant reduction in MI, stent thrombosis, or stroke.

Given that the curves in IAMI diverged early and stayed apart over time, the cardiovascular benefit of the flu shot likely goes beyond vaccination and is perhaps related to inflammation or coagulation, suggested Filippo Crea, MD, of Fondazione Policlinico Universitario A. Gemelli IRCCS in Rome.

Indeed, data accumulating for more than a decade show that after someone recovers from acute influenza, the inflammatory response continues over several weeks, putting individuals at increased risk of events like MI and stroke, said William Schaffner, MD, of Vanderbilt University School of Medicine in Nashville, in an interview.

ESC session chair Yvo Smulders, MD, PhD, of Vrije Universiteit Medical Center in Amsterdam, said the idea that influenza vaccines provide inflammatory pre-conditioning will need to be supported by more studies.

For now, "I hope [IAMI] provides additional motivation for influenza vaccination, especially this year despite all the attention that will be on COVID vaccine boosters," said Schaffner, who is also medical director of the National Foundation for Infectious Diseases. "There are people with vaccine fatigue, and they don't want to hear about another respiratory virus that they have to get a vaccine for."

"These are separate risks," he maintained. "Now we have good vaccines against these two very bad respiratory viruses."

FDA gave full approval to Pfizer's mRNA vaccine against SARS-CoV-2 last week.

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