Can Evusheld Increase Cardiovascular Events
InpharmD™ Clinical Literature Summaries — S4E1
Welcome back for Season 4! We like to throw new twists at you guys each season, so here’s what we’ve got in store. When one clinician has a clinical question, there’s a 40% chance another clinician has that exact same question. That’s why this season, we are going to take some of our most commonly asked drug information questions and break down the evidence for you all.
To lead things off, we’ve been getting lots of questions about Tixagevimab and Cilgavimab or as many of you know it, Evusheld . Specifically, you all have been wondering about the risk of cardiovascular events with this drug.
Just a little background here… so, Evusheld is a combination of two monoclonal antibodies that bind to the spike protein on COVID-19. They prevent the virus from binding to and infecting our cells. This drug is currently being used for pre-exposure prophylaxis in patients at high risk for a poor outcome from COVID-19.
As many of you know, the package insert for Evusheld has a warning about the possible increased risk of cardiovascular events with this medication. The warning comes from the original PROVENT trial where they did a post-hoc analysis and found that patients in the Evusheld group had 3 times the rate of cardiovascular events as placebo, but these rates were quite low overall with Evusheld at 0.6% and placebo at 0.2%. Unfortunately, no statistical analysis was done so we don’t know if this was a significant difference. We can’t explain away this difference with baseline characteristics as there didn’t appear to be a difference in common cardiac risk factors like obesity, diabetes or smoking between groups.
One thing all patients who experienced a cardiac event had in common was cardiac disease or risk factors for cardiac disease at baseline. There also didn’t seem to be a temporal pattern to when these events happened relative to administration of the antibody cocktail.
The PROVENT trial did use the 300 mg dose of Evusheld, which many of you know is now outdated given the emergence of new variants. A 600 mg dose is now used, so we have to ask: Could cardiac events be dose dependent?
Well the ongoing TACKLE trial used the higher dose of 600 mg and found a rate of <1% for both sudden cardiac death and acute heart attack or heart failure in the Evusheld group, relative to 0% in the placebo group. It sure doesn’t seem like the higher dose is causing an increase in events, but there were literally only 2 events total out of over 400 patients in the Evusheld group, so it’s hard to know.
All this being said, its important to note that we don’t have enough data to determine a causal relationship between Evusheld and cardiac events. While there is certainly cause for some concern and caution, we just don’t have the data to have a full on freak out about this.
If more data comes out, you’ll be sure to hear about it from us, but in the meantime as it always seems to be in medicine, this becomes a risk vs benefits discussion. Patients with baseline cardiovascular disease or significant cardiac risk factors may be at a higher risk for cardiac events after Evusheld. But it’s important to take into account their risks for severe COVID-19 as well. And don’t forget, COVID-19 itself seems to be associated with cardiovascular issues too such as myocarditis. Sorry, but if you hadn’t realized it yet, medicine isn’t always black and white!
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The InpharmD Podcast is an independent production of InpharmD. Check out more evidence-based information at inpharmd.com
Other papers/resources used:
Montgomery H, Hobbs FDR, Padilla F, et al. Efficacy and safety of intramuscular administration of tixagevimab–cilgavimab for early outpatient treatment of COVID-19 (Tackle): a phase 3, randomised, double-blind, placebo-controlled trial. The Lancet Respiratory Medicine. Published online June 2022:S2213260022001801. doi:10.1016/S2213–2600(22)00180–1
Levin MJ, Ustianowski A, De Wit S, et al. Intramuscular AZD7442 (Tixagevimab-Cilgavimab) for Prevention of Covid-19. N Engl J Med. 2022;386(23):2188–2200. doi:10.1056/NEJMoa2116620