December 8, 2022

To watch more from Medscape for free visit here:

Hi i’m dr michelle o’donoghue i’m here at esc congress 2022 we are back in person which is great there’s been a lot of terrific science and and one of the late-breaking clinical trials that will be presented will be by my friend and colleague dr david berg who is an investigator at the timmy study group and he’ll be presenting the top-line results of a trial called

Covet pact on which i i am a co-author but i thought it was very interesting to talk about this topic in general is it it still remains an interesting one welcome david thank you michelle it’s pleasure to be here thank you for having me so let’s talk a little bit about the question being asked you know why do we think about clots in the context of covid yeah

I know i think that’s a great question um so so relatively early on in the pandemic it was appreciated that patients with cobit 19 have an increased risk of developing blood clots and that risk is particularly concentrated in patients who require icu level care the exact mechanisms underpinning that increased thrombotic risk are still being sorted out but but

There’s probably multiple things that contribute to it and one of the interesting findings has been that that increased thrombotic risk is held constant over time so even with the introduction of effective therapies and vaccines um if you benchmark the risk of thrombosis and cova-19 to other viral infections like influenza that increase their harmonic risk has

Been constant over time yeah it’s interesting it does raise many questions about you know whether or not the type of virus like has there been any change over time in terms of clotting risk since the start of cobit towards more recent cases yeah no i i think um it’s that’s a great question and i the uh there really has not so some of the early epidemiologic data

Suggested very high rates but that came from case reports in case series um so within a few months with when larger epi studies were published uh it was appreciated that rates of thrombosis in icu patients were on the order of 10 to 30 percent um and even with the introduction of effective therapies that’s remained the case right so so what does the evidence show

So far leading up to covet pack what do we know about different treatments and their effectiveness and their safety yeah we as you can imagine there was a lot of uh enthusiasm to try to understand the effect of anti-thrombotic therapy uh in covet 19. once it was appreciated that there was an increased risk of thrombosis and so there’s been a number of randomized

Trials to date that have answered exactly that question or explore that question looked at increased intensity anticoagulant therapy or antiplatelet prophylactic strategies and i’d say that the primary results of those studies have been uh mixed in in large part because of differences in study designs and the patient populations uh and and in particular the study

Endpoints um it in particular was one large study called the the multi-platform trial which combined a couple different trial platforms um and there were separate studies in critically ill and non-critically ill patients and the primary endpoint in that study was an organ failure endpoint so it was number of days alive uh off organ support through 21 days uh

And surprising there were different results in the critically ill and non-critically ill patient population so in non-critically ill patients the study was stopped for superiority of full dose anticoagulation both of them had the same design therapeutic dose anticoagulation as compared with standardized prophylactic anticoagulation and there was a benefit of full

Dose anticoagulation in the the non-critically ill patients but in the critically ill patients that was not seen and so that’s led to some consensus guidelines based on sort of relatively uh uncertain evidence to to use full dose anticoagulation in patients with who are hospitalized but not an icu but then when they’re in the icu to use standard dose prophylaxis

Well so that’s that sets the stage for cova pact so where did covet pact think it could make an impact and what patient population did you study yeah so covid pact was a two by two factorial randomized control trial um in critically ill patients with cova 19 so focused on patients who required icu level care and that included patients who were either physically

Admitted to the icu or who were receiving icu level care outside of the icu advanced respiratory support vasopressor support mechanical circulatory support and they were randomized in a one-to-one allocation ratio to either treatment full dose anticoagulation or standard dose prophylactic anticoagulation there was an additional randomization to either clopidogrel

Or no antiplatelet therapy if patients were not already on antiplatelet therapy and then patients were followed through hospital discharge or day 28 post randomization what was different about covet pact compared to the the multi-platform trial is the focus was on thrombotic events so the primary efficacy endpoint was a composite of venous and arterial thrombotic

Events um and that was i think probably the the biggest uh design difference in the studies yeah well it makes a lot of sense right if we’re thinking about anti-thrombotic and anti-platelet therapy you know i can understand the interest in looking at really a clot outcome specifically so what did the results show yeah so the the uh the results were very exciting

I’m obviously biased but uh we enrolled 400 patients uh and for the the anticoagulation randomization um that when comparing photos anticoagulation to standard dose prophylactic anticoagulation there was a 44 relative reduction in the risk of the primary advocacy endpoint which was composite of venous and arterial thrombotic events that was a significant reduction

For the comparison of clopidogrel versus no antiplatelet therapy uh there was no benefit of clopidogrel uh we in addition to looking at thrombotic endpoints we looked at safety endpoints uh and so as you might expect uh with the increased with the reduction in thrombotic events there was an increased risk in bleeding so there was two safety endpoints the first

Was uh fatal or life-threatening bleeding fortunately there were no fatal bleeding events in the study um there were numerically more life-threatening bleeds in patients who were were treated with full dose anticoagulation um that was not a statistically significant difference because there were such few events but there was a numeric increase but there was an

Increase in gusto moderate bleeding which refers to bleedings that results in any transfusion but without hemodynamic instability so it does appear that there is a bit of a tradeoff between a reduction in thrombotic events and an increase in in bleeding um that is not hemodynamically significant bleeding yeah i think it’s an important contribution and the fact

That the anti-platelet therapy had no impact um you know i think is really notable as well and perhaps provides some insights into the pathobiology of what’s going on at the clot level yeah so in your practice now when you’re attending in the icu do you think that this would change your approach to a critically ill covid patient you know do you think that you

Would be treating them across the board with a full dose anticoagulant or you know because of the bleeding concerns are you going to be more selective and do you have any advice for people about you know any patient groups who perhaps have the the better net clinical benefit yeah no i think that’s exactly the question that we’re all wondering about and one that

I have grappled with a lot over the last two years um i would say that that uh what covid pact supports is the efficacy of anticoagulation or full dose anticoagulation for the reduction of thrombotic events and and i think it particularly helps because many clinicians have been scratching their heads about how to approach this difference between moderately ill

Patients and critically ill patients should we right now guidelines suggest that you should put patients on photos in a coagulation when they’re admitted to the hospital but then when they get sick do we stop it what about that middle zone patient who’s on high flow nasal cannula how do we handle that and i think what what we can say now is with some confidence

Is that continuing photostatic coagulation or starting folders in a coagulation when a patient goes to the icu is going to reduce their thrombotic risk it may not affect an organ failure endpoint but it’s going to reduce their thrombotic risk i think you raise the obvious question which is is that true for everybody and i think we have to be careful about patient

Selection and i think it’s helpful to think about who was excluded from covet pact so if patients were severely coagulopathic if they were severely thrombocytopenic they didn’t end up in the study if they were on dual and platelet therapy in which case adding folders anticoagulation would give them triple therapy they were excluded so those patients are are not

Ones i would use photosynthetic coagulation in um and then when we looked at patients who did bleed on photosynthesis they tended to be quite a bit older uh than patients uh who did not believe and so that’s a story that we’ve learned many times but i would have some i would be careful in using it in elderly patients that’s important and i think that you know

Always taking a look at clinical trial results in terms of who was excluded and who was included in their patient population is always an important thing to do well thank you again for for sharing these exciting results i’m sure we’ll see many analyses down the road as you continue to explore the data set but uh congratulations thank you michelle it’s great to be

Here signing off from medscape this is dr michelle o’donoghue it’s

Transcribed from video
COVID-PACT: What's the Best Anticoagulant Strategy for Critically Ill Patients With COVID-19? By Medscape