The high-dose influenza vaccine fails to reduce death and CV events in the high-risk cohort

According to the INVESTED study results, injection of a high-dose influenza vaccine did not affect all-cause death, cardiac or pulmonary hospitalization compared to a lower dose in patients with previous myocardial infarction or HF.

Orly Vardeny

“A meta-analysis of randomized clinical trials showed that influenza vaccination was associated with a lower risk of major adverse cardiovascular events than lack of vaccination,” Orly Vardeny, PharmD, MS, associate professor of medicine at the University of Minnesota and the Minneapolis Veterans Affairs Health Care System, said during a press conference at the American Heart Association’s virtual science sessions. “The high-dose influenza vaccine, currently approved for individuals aged 65 and over, contains four times the amount of antigen or hemagglutinin than the standard dose vaccine and has been shown to reduce the risk of laboratory-confirmed symptomatic influenza and a large clinical trial compared to the standard dose. However, the Advisory Committee on Immunization Practices does not preferentially recommend one vaccine formulation over another. “

For this study, the researchers enrolled 5,260 patients (mean age, 66 years) who had had a MI in the previous year or hospitalized for heart failure in the previous 2 years, plus another risk factor to assess whether the flu vaccine a high dose would have improved clinical outcomes among high-risk patients compared to the standard dose. Participants were randomly assigned to either a yearly high-dose trivalent inactivated influenza vaccine or a standard-dose quadrivalent inactivated influenza vaccine for three influenza seasons.

The primary endpoint was death from all causes or cardiopulmonary hospitalization within each influenza season. Secondary endpoints included CV death or hospitalization, first cardiopulmonary hospitalization or death from all causes, death from all causes, and total cardiopulmonary hospitalizations and death from all causes.

Researchers found no significant differences in all-cause mortality or cardiopulmonary hospitalization between patients who received the high-dose flu vaccine versus those who received the lowest dose (HR = 1.06; 95% CI, 0 , 97-1.17; P. = 0.21).

There was also no difference between groups in each component of the secondary endpoint:

• CV death or hospitalization (HR = 1.08; 95% CI, 0.98-1.19; P. = .16);
• first cardiopulmonary hospitalization or death from all causes (HR = 1.06; 95% CI, 0.97-1.16; P. = .24);
• all cause death (HR = 1.01; 95% CI, 0.84-1.21; P. = 0.96); is
• total cardiopulmonary hospitalizations and death from all causes (HR = 1.04; 95% CI, 0.94-1.15; P. = .44).

“The high-dose inactivated influenza vaccine did not reduce all-cause death or hospitalization from cardiac or pulmonary causes compared to the standard-dose vaccine,” Vardeny said at the news conference. “Individuals who received a high-dose vaccine noted a slightly higher incidence or frequency of self-limiting adverse effects than the standard dose vaccine and there were rarely serious adverse reactions in either group.”

Additionally, patients who received the high-dose vaccine reported a higher frequency of injection site pain (26.1% versus 19.1%; P. <.001), swelling (5.5% vs. 3.3%; P. <.001) and myalgia (14% vs 11.8%; P. = .007).

“We compared two active vaccine formulations in a high-risk population, and both are known to reduce flu disease, so receiving any flu vaccine and high-risk patients may have been protective and limiting the potential benefit of doses. elevated vaccine in the reduction of cardiopulmonary events, “Vardeny said at the news conference. “Importantly, these findings do not detract from previous studies showing the benefit of the high-dose vaccine in reducing influenza disease, nor do they minimize the importance of influenza vaccination in patients with high-risk cardiovascular disease, for whom influenza vaccination remains strongly recommended “.

Harriette GC Van Spall

Harriette GC Van Spall, MD, MPH, FRCPC, associate professor of medicine and scientist at the Population Health Research Institute at McMaster University in Hamilton, Ontario, Canada, said in a post-press conference discussion, “The strengths of the study were that it was broad and well designed with a active comparator and the first of its kind in patients with established heart failure and cardiovascular disease. Multiple influenza seasons were included in the analysis, indirectly taking into account variability in infection rates and strains during influenza seasons. Clinically endpoints were chosen. relevant and there were higher than expected event rates, indicating the well-designed nature of the study and likely adequate statistical power to answer the research question.

“There are several gaps that still need to be addressed. How can we reconcile the findings of this study with previous studies, especially a large study that established the superiority of the high-dose flu vaccine over the standard-dose vaccine among older patients, “Van Spall said.” Seasonality would have Did high-dose vaccination play a role in mitigating the severity of the COVID-19 infection? Flu vaccine in specialized cardiovascular clinics and 24/7 pharmacies is more effective in implementing flu vaccination? Do incentives matter? And how can we reliably predict seasonal flu strains for more effective vaccine matches? “

Perspective

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Martha Gulati, MD, MS, FACC, FAHA

INVESTED does not detract from previous research where high-dose vaccines are effective. There are many positive things in the study. The researchers did the right thing by looking at three flu seasons and tried to pick a high-risk group, although I have some criticisms of that.

There was no difference between the vaccine doses, but I was surprised at what the comparison was. The study used a high-dose trivalent-inactivated vaccine and compared it to a standard dose – not another trivalent vaccine, but rather a quadrivalent vaccine. I’m surprised, because the quadrivalent vaccine is what we normally use. Why didn’t the high-dose vaccine cover the additional strain as well? This could be why no difference was observed.

I was disappointed with the under-representation of women. Only about a quarter of this study group were women and they are a high-risk group. As for the race, it was predominantly a white population.

We would also like to know how high-risk these patients were. This cohort previously had MI or HF because it was a qualifying event, but what kind of people were enrolled? If they are very compliant and very well managed medically, this could represent the type of person who would also choose to undergo a flu shot.

Another point about this population not mentioned and which I hope will come out in an article is that these patients resided in the community? Were they in nursing homes or some kind of assisted living facility? If you are looking at an elderly population, we are not only concerned with COVID-19 but also with the flu. Where and how you live exposes you to greater risk. So there may be a difference based on the life situation.

INVESTING is important because while we’re all still focused on COVID-19, the flu is a big deal and we know it increases CVD in our CVD patients. If they get the flu, they are the sickest patients. One strategy of the American College of Cardiology and the AHA is to vaccinate our heart patients. But if there was a more effective vaccine that covered more and kept our patients safer, we would like to use it.

At present, the high-dose vaccine is not widely available. I have never been able to order the high dose over the standard doses. We get everything that is available. People go to a variety of places to get the flu shot and if a high dose was available, I don’t think people would know if they were taking it or not.

We need to know more about the effects of high-dose vaccines so that we can use them effectively, but maybe INVESTED didn’t choose the right high-dose vaccine.

Martha Gulati, MD, MS, FACC, FAHA

Division Head of Cardiology

University of Arizona College of Medicine – Phoenix

Chief Editor

CardioSmart of the American College of Cardiology

Disclosures: Gulati does not report any relevant financial information.

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