Erin Michos, MD, on Reducing CVD Outcomes With Influenza Vaccination

In this podcast, Erin Michos, MD, talks about her latest study on how the influenza vaccine effects mortality and morbidity outcomes among patients with established cardiovascular disease.

Additional Resources:

• Yedlapati S, Khan SU, Talluri S, et al. Effects of influenza vaccine on mortality and cardiovascular outcomes in patients with cardiovascular disease: a systematic review and meta-analysis. Paper presented at: American Heart Association Scientific Sessions 2020; November 13-17, 2020; Virtual. https://eventpilotadmin.com/web/planner.php?id=AHA20 
• Behrouzi B, Araujo Campoverde MV, Liang K, et al. Influenza vaccination to reduce cardiovascular morbidity and mortality in patients with COVID-19: JACC State-of-the-Art Review. J Am Coll Cardiol. 2020;76(15):1777-1794. doi:10.1016/j.jacc.2020.08.028
• INfluenza Vaccine to Effectively Stop Cardio Thoracic Events and Decompensated Heart Failure (INVESTED). ClinicalTrials.gov. Accessed November 11, 2020. ClinicalTrials.gov identifier NCT02787044. https://clinicaltrials.gov/ct2/show/NCT02787044
• Study on the Effect of Influenza Vaccination After Heart Attack on Future Cardiovascular Prognosis (IAMI). ClinicalTrials.gov. Accessed November 11, 2020. ClinicalTrials.gov identifier NCT02831608. https://clinicaltrials.gov/ct2/show/NCT02831608
• Influenza Vaccine To Prevent Adverse Vascular Events (RCT-IVVE) (RCT-IVVE). ClinicalTrials.gov. Accessed November 11, 2020. ClinicalTrials.gov identifier NCT02762851. https://clinicaltrials.gov/ct2/show/NCT02762851

Erin D. Michos, MD, is the director of women’s cardiovascular health at Johns Hopkins University School of Medicine in Baltimore, Maryland.

TRANSCRIPT:

Amanda Balbi: Hello everyone, and welcome to another installment of Podcasts360—your go-to resource for medical news and clinical updates. I’m your moderator, Amanda Balbi with Consultant360 Specialty Network.

Influenza infection is known to be associated with increased morbidity and mortality among patients with cardiovascular disease. To better understand how the influenza vaccine affects those with established cardiovascular disease, researchers conducted a systematic review and meta-analysis that included 16 studies and 237,058 participants.

My guest today is the lead author of the study, which is also being presented at the American Heart Association Scientific Sessions 2020, Dr Erin Michos is the director of women’s cardiovascular health at Johns Hopkins University School of Medicine.

Thank you for joining me today, Dr Michos.

Erin Michos: Thank you for letting us share our study, which I'll mention is being presented by the first author Dr Siva Yedlapati at the American Heart Association meeting in November.

Amanda Balbi: To start, can you give us an overview of your study and how it came about?

Erin Michos: Influenza is a big problem in the United States. In the year 2018-2019, an estimated 35 million people were infected with influenza with about 500,000 patients hospitalized and 34,000 deaths.

The World Health Organization estimates that influenza that kills as many as 650,000 people every year. So, influenza is actually within the top 10 leading causes of death of people of all ages.

We already know that the American Heart Association and the Centers for Disease Control and Prevention have recommended influenza vaccine really in all patients above the age of 6 months, but particularly in patients with cardiovascular disease. Yet the uptake of this recommendation is pretty low. We know that only about 45% of adults were vaccinated with influenza vaccine. Why does the American Heart Association have this strong class I recommendation when we know that there's actually a strong link between influenza and heart disease risk.

First of all, the presence of having cardiovascular disease like coronary disease or heart failure that's just a risk marker for a worst prognosis in the setting of any viral infection. It’s associated with more morbidity and mortality. We see the same thing with COVID-19 as well.

But of note, it may be that viral infections seem to be independent risk factors for cardiovascular events like heart attacks in a prior study in the New England Journal of Medicine. The authors found that there was a 6-fold increased risk of a heart attack within 7 days of a confirmed influenza infection.

There's a lot of mechanisms for this, maybe that the stress of having a viral infection like influenza increases the metabolic demand, and so people with underlying cardiovascular disease can't keep up with the increased metabolic stressors.

But it also may be that the virus directly precipitates an acute cardiovascular event by stimulating a potent inflammatory response, which can trigger acute plaque rupture causing heart attacks and strokes.

It also can cause global myocardial depression, and the influenza virus can also directly infect tissues of the heart, lung, and blood vessels and can cause a myocarditis picture. Knowing this risk, it's really important for the influenza vaccine. And so, we set out in our unique meta-analysis to really generate consensus and understanding regarding the cardiovascular benefits.

We tried to combine real-world data from observational studies, as well as data from randomized clinical trials, to understand the magnitude of benefit of efficacy of influenza vaccine, specifically in patients with underlying cardiovascular disease.

Amanda Balbi: Let’s talk about the results of your study. What did you find, and how might those findings impact clinical practice?

Erin Michos: Sure. Upon our review of the literature, we found 16 studies that included 4 randomized clinical trials and 12 observational studies that together contained over 200,000 patients who were followed for about 20 months. These studies compared influenza vaccine to a control or to usual care.

The use of influenza vaccine was associated with a 28% lower risk of all-cause mortality in our meta-analysis, an 18% lower risk of cardiovascular mortality, and a 13% lower risk of having a major adverse cardiovascular event.

This is really significant. These findings help to promote health care professionals and policymakers to more strongly advocate for influenza vaccine for secondary prevention of cardiovascular outcomes.

This is a pretty substantial reduction—a 28% lower risk of death. And so, given these marked reductions in mortality and given what we know about the safety and feasibility and low cost of influenza vaccine, we really feel like this should be more strongly considered alongside other cardiovascular prevention therapies.

We know that cardiologists are less likely to stock influenza vaccine in their clinical practices. They often recommend patients to get it elsewhere or through their primary care doctors. But, again, I think cardiologists as well as everybody should be paying more attention to whether their patients are being vaccinated, just because of the marked benefits associated with it for both cardiovascular risk reduction, as well as a meaningful mortality reduction.

Amanda Balbi: In your opinion, do you think COVID-19 will affect cardiovascular disease the same way as influenza did in your study?

Erin Michos: Yeah, so we have already seen in the COVID-19 pandemic that individuals with underlying cardiovascular disease, hypertension, diabetes, obesity are at greater risk for poorer outcomes in mortality in the setting of COVID infection.

Currently, we think that any kind of viral infection, including COVID, can have some of these same increased risks for direct myocardial injury. Again, increased risk of triggering a plaque rupture event, causing direct myocardial infection, and overall increasing metabolic demand so that individuals who have underlying cardiovascular disease are a greater risk for a type 2 myocardial infarction.

At this current time, we don't have a definitive COVID-19 vaccine available, so we recommend everybody in particular to get vaccination against influence of this year, because it will reduce the risk of influenza and may offer some incremental cardiorespiratory protection until a definitive COVID-19 vaccine is available.

It's bad enough dealing with the COVID pandemic, and if we add the usual seasonal influenza infection at a time when our ICUs are already over full and our hospital and health care system are under stress, it's going to be very difficult to manage the regular influenza infections that we see every year on top of the current pandemic.

So, we this year, more than ever, need to be more effective in implementing influenza vaccination and trying to mitigate the risk of influenza infection on top of what we're dealing with with the COVID pandemic.

Although, I am a little optimistic that some of the measures that were using, such as mask wearing and handwashing and a lot of these public health strategies that we're recommending for COVID protection, should also help reduce the risk of flu exposure as well.

While we studied cardiovascular disease patients in our meta-analysis for the study, because they're the ones who are at greater risk and the most vulnerable for a worse outcome in the setting of influenza. But again, the CDC recommends everybody, even for people as young as 6 months of age, to get the influenza vaccine.

So, I hope that we all can do our part to keep ourselves and our public health, our community safe.

Amanda Balbi: What is the next step in your research?

Erin Michos: It's not what we are doing ourselves, but I just want to point out—because I think it's really important—that there are 3 large, ongoing influenza clinical trials that are powered for cardiovascular outcomes.

The reason why we did this meta-analysis is that prior studies are small, and there was some heterogeneity in the data. And so, we did a meta-analysis trying to pull all this data together.

But there are 3 major trials now that are enrolling thousands of individuals that are actually being powered for cardiovascular outcomes to really determine the potential of cardiovascular protective effect of influenza vaccine.

These involve populations of patients who either have heart failure or have had an acute myocardial infarction or history of prior cardiovascular disease. So, I await those trials as well.

Amanda Balbi: Great. Thank you again for speaking with me today, Dr Michos.

Erin Michos: Thank you so much for your interest in our study. And again, I recommend everybody to get their influenza shot every year, but particularly this year, in particular with the current COVID pandemic going on in the background.