American Heart Association

American Heart Association

Source:

Vardeny O, et al. LBS.08: AHA goes viral: COVID-19, influenza vaccines, and cardiovascular disease. Presented at: American Heart Association Scientific Sessions; Nov. 13-17, 2020 (virtual meeting).

Disclosures: Vardeny reports she received research support from AstraZeneca, FDA and NIH-NHLBI; is a consultant for Novartis and Sanofi-Pasteur; and received personal fees from the AHA. The INVESTED trial was supported by grants from the NHLBI and received additional funding and vaccine from Sanofi-Pasteur. Van Spall reports no relevant financial disclosures.
November 17, 2020
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INVESTED: High-dose influenza vaccine fails to reduce death, CV events in high-risk cohort

Source:

Vardeny O, et al. LBS.08: AHA goes viral: COVID-19, influenza vaccines, and cardiovascular disease. Presented at: American Heart Association Scientific Sessions; Nov. 13-17, 2020 (virtual meeting).

Disclosures: Vardeny reports she received research support from AstraZeneca, FDA and NIH-NHLBI; is a consultant for Novartis and Sanofi-Pasteur; and received personal fees from the AHA. The INVESTED trial was supported by grants from the NHLBI and received additional funding and vaccine from Sanofi-Pasteur. Van Spall reports no relevant financial disclosures.
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Injection of a high-dose influenza vaccine did not affect all-cause death, cardiac or pulmonary hospitalization compared with a lower dose in patients with prior MI or HF hospitalization, according to findings from the INVESTED trial.

Orly Vardeny

“A meta-analysis of randomized clinical trials showed that influenza vaccination was associated with a lower risk for major adverse cardiovascular events compared with no vaccination,” Orly Vardeny, PharmD, MS, associate professor of medicine at the University of Minnesota and Minneapolis Veterans Affairs Health Care System, said during a press conference at the virtual American Heart Association Scientific Sessions. “High-dose influenza vaccine, which is currently approved for individuals aged 65 or older, contains four times the amount of antigen or hemagglutinin compared with standard-dose vaccine and has shown to reduce the risk for laboratory-confirmed symptomatic influenza and a large randomized clinical trial compared with standard dose. However, the advisory committee on immunization practices does not preferentially recommend one vaccine formulation over another.”

Flu vaccine
Source: Adobe Stock

For this trial, investigators enrolled 5,260 patients (mean age, 66 years) who experienced an MI in the previous year or HF hospitalization in the previous 2 years in addition to one other risk factor to evaluate whether high-dose influenza vaccine would improve clinical outcomes among high-risk patients compared with the standard dose. Participants were randomly assigned to an annual high-dose trivalent inactivated influenza vaccine or a standard-dose quadrivalent inactivated influenza vaccine for three influenza seasons.

The primary endpoint was all-cause death or cardiopulmonary hospitalization within each influenza season. The secondary endpoints included CV death or hospitalization, first cardiopulmonary hospitalization or all-cause death, all-cause death and total cardiopulmonary hospitalizations and all-cause death.

Researchers found no significant difference for all-cause mortality or cardiopulmonary hospitalization among patients who received the high-dose influenza vaccine compared with those who received the lower dose (HR = 1.06; 95% CI, 0.97-1.17; P = .21).

There was also no difference between the 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 all-cause death (HR = 1.06; 95% CI, 0.97-1.16; P = .24);
  • all-cause death (HR = 1.01; 95% CI, 0.84-1.21; P = .96); and
  • total cardiopulmonary hospitalizations and all-cause death (HR = 1.04; 95% CI, 0.94-1.15; P = .44).

“High-dose inactivated influenza vaccine did not reduce all-cause death or hospitalizations for cardiac or pulmonary causes compared with standard-dose vaccine,” Vardeny said during the press conference. “Individuals who received high-dose vaccine noted a modestly higher incidence or frequency of self-limiting adverse effects compared with standard-dose vaccine and there were infrequent serious adverse reactions in both groups.”

In addition, patients who received the high-dose vaccine reported an increased frequency of injection site pain (26.1% vs. 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 very high-risk population, and both of these are known to reduce influenza illness, thus receipt of any influenza vaccine and high-risk patients may have been protective and limit the potential benefit of high-dose vaccine in reducing cardiopulmonary events,” Vardeny said during the press conference. “Importantly, these results do not detract from prior trials showing benefit of high-dose vaccine on reducing influenza illness, nor do they minimize the importance of influenza vaccination in patients with high-risk cardiovascular disease, for whom influenza vaccination remains strongly recommended.”

Harriette G.C. Van Spall

Harriette G.C. 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 during a discussion after the press conference, “The strengths of the trial were that it was large and well designed with an active comparator group, and a first of its kind in patients with heart failure and established cardiovascular disease. Multiple influenza seasons were included in the analysis, indirectly accounting for variability in infection rates and strains across influenza seasons. Clinically relevant endpoints were chosen, and there were higher than expected event rates, pointing to the well-designed nature of the study and likely adequate statistical power to answer the research question.

“There are several gaps that remain to be answered. How can we reconcile findings of this trial with prior trials, particularly a large trial that established the superiority of high-dose influenza vaccine over standard-dose vaccine among older patients,” Van Spall said. “Could seasonality have made a difference? Does high-dose vaccination have a role in attenuating the severity of COVID-19 infection? How do we close gaps in racial, ethnic, socioeconomic and geographic disparities in influenza vaccination and infection rates? Is delivering the influenza vaccine in specialty cardiovascular clinics and 24/7 pharmacies more effective in implementing influenza vaccination? Do incentives matter? And how do we reliably predict seasonal influenza strains for more effective vaccine matches?”