Cardiovascular risks with Tixagevimab and Cilgavimab (Evusheld)

The FDA has a specific warning about Evusheld - it should be include in the informed consent, esp. since the prophylaxis use is off-label:

Warnings/Precautions

Concerns related to adverse effects:

Cardiovascular events: A higher rate of serious cardiovascular adverse events, including myocardial infarction, was observed among recipients of tixagevimab and cilgavimab, compared to placebo. All patients who experienced cardiac events had cardiac risk factors and/or a history of cardiovascular disease, and there was no clear temporal pattern. Consider potential risk and benefit in patients with a history of cardiovascular disease and advise patients to seek immediate medical attention if they experience signs/symptoms of a cardiovascular event (FDA 2021).

In the post-hoc analysis of PROVENT, the incidence of serious cardiac adverse events (eg, myocardial infarction, cardiac failure, arrhythmia) was higher in the antibody group than in the placebo group (0.6% vs 0.2%). One person who received the antibodies died of a myocardial infarction. There was no clear temporal relationship between antibody administration and cardiac adverse events.

The trial incidence of serious cardiac events was 0.6% with Evusheld according to JAMA (https://jamanetwork.com/journals/jama/fullarticle/2788354)

As a comparioson, the AMI risk with IVIG is limited to case reports, here is an example and a review: https://pubmed.ncbi.nlm.nih.gov/16288078/

Again, from the FDA (https://www.fda.gov/media/154701/download):

“Cardiovascular Events: A higher proportion of subjects who received EVUSHELD versus placebo reported myocardial infarction and cardiac failure serious adverse events. All of the subjects with events had cardiac risk factors and/or a prior history of cardiovascular disease, and there was no clear temporal pattern. A causal relationship between EVUSHELD and these events has not been established.

Consider the risks and benefits prior to initiating EVUSHELD in individuals at high risk for cardiovascular events, and advise individuals to seek immediate medical attention if they experience any signs or symptoms suggestive of a cardiovascular event. (5.3)”

Of note, among the PROVENT trail participants less than 1% had an immunodeficiency disorder, therefore, strictly speaking, the effect of Tixagevimab and Cilgavimab (Evusheld) in patients with immunodeficiency disorders was not studies in this trial.

References:

https://jamanetwork.com/journals/jama/fullarticle/2788354

https://www.fda.gov/media/154702/download