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High-dose influenza vaccine in patients with CVD

Presented by
Prof. Orly Vardeny, University of Minnesota Medical School, USA
AHA 2020
A high-dose, trivalent influenza vaccine was not more effective than the standard-dose quadrivalent vaccine at reducing the risk of death or hospitalisation for heart-related or lung-related causes in patients with a history of recent hospitalisation for acute myocardial infarction (MI) or heart failure (HF). This was the main conclusion from the INVESTED study [1,2].

In patients with underlying cardiovascular disease, influenza is temporally associated with cardiopulmonary morbidity and mortality, including MI, hospitalisations for HF, and death. Influenza vaccination reduces adverse clinical outcomes and is recommended annually. However, individuals with cardiovascular disease often mount a less effective vaccine-induced protective response [2]. The same holds true for older patients (aged ≥65 years) for whom a high-dose vaccine is approved in the USA.

The INVESTED study (NCT02787044) was designed to test if a high-dose vaccine reduces the risk of cardiopulmonary events compared with a standard dose. INVESTED was a pragmatic, randomised, double-blind, phase 4 trial of high-dose trivalent versus standard-dose quadrivalent influenza vaccination in patients who had been hospitalised for acute MI or HF in the past 2 years. Participants also had at least one additional risk factor such as smoking, diabetes, stroke, or peripheral artery disease.

Prof. Orly Vardeny (University of Minnesota Medical School, USA) presented the results. A total of 5,260 participants were enrolled during the 2016/2017 (n=494), 2017/2018 (n=2,506), and 2018/2019 (n=2,264) influenza seasons. Mean age was 65.5 (±12.6) years, 72% were male, and 63% had HF. Patients were randomised 1:1 to high-dose or standard-dose influenza vaccine, with a total of 7,154 vaccination-years. “We found that the higher dose influenza vaccine was not more effective than the standard dose in lowering the risk of death or hospitalisations due to heart or lung-related disease,” Prof. Vardeny said. The rate of mortality or hospitalisations for cardiac or pulmonary causes was 44.5 per 100 patient-years in the high-dose vaccine group versus 41.9 per 100 patient-years in the standard-dose group. Overall, there were few serious side effects in either vaccine group. In the high-dose vaccine group, injection-related side effects such as pain, swelling, and muscle aches were more prevalent. Whether the higher dosed vaccine was superior in reducing overall influenza infections in study participants was not recorded. Hospitalisation rates for influenza were similar between the groups. These outcomes were adjudicated by an independent clinical events committee.

Both formulations may reduce the risk for heart and lung hospitalisations similarly, Prof. Vardeny commented. Another possible explanation for the results, she suggested, is that the incremental benefit of one vaccine over the other could not have overcome the already high underlying risk in this population. She also noted that the extra influenza strain present in the standard-dose vaccine might have offset the benefit of the higher dose. “Most importantly, these data do not impinge on the very strong recommendation that all heart disease patients should be vaccinated for influenza,” Prof. Vardeny concluded. She added this is even more important this year, when influenza will be co-circulating with the SARS-CoV-2 virus.

    1. Vardeny O, et al. High Dose versus Standard Dose Influenza Vaccine in Patients With High Risk Cardiovascular Disease: Results From the Invested Trial. LBS.08, AHA Scientific Sessions 2020, 13–17 Nov.
    2. Vardeny O, et al. JAMA. 2021;325(1):39–49.


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