Bleeding Risk with Apixaban vs Rivaroxaban for Acute VTE (COBRRA), Left Atrial Appendage Closure vs Medical Therapy for Atrial Fibrillation (CLOSURE-AF)

Welcome to last week in medicine. I'm Austin Rupp. I'm here with Dr. Stephen Jenkins. Hello, Stephen. How are you? Hey, how you doing Austin? I'm good. I'm good. It's a Friday, March 26th.

7th, 2026. Gas prices are going up. We're locked in. How are we going that? They are soaring. Hey, you know what? In an

intermentable Middle Eastern conflict. And here we go. And it's crazy because on our last episode that you and I did

together, that was like one of the last things you said was we might be at war with Iran. And I was like, yeah,

they've been saying that for years, but you were right. I was wrong. It happened epic fury the stupidest name in the

history. Anyway, okay, you know what though? I'm like hoping for like $9 a gallon gas like just all the

way go all the way to the moon. What else should we talk about? I was in Utah recently. We got together. That

was nice. Good to see you. No snow. Yeah, man. It's spring and wild. I went up to Brighton ski resort on

Wednesday and like, you know, everyone's like in t-shirts and it was just slush everywhere. Really

interesting winner. Yeah. Colorado River. Yeah, Colorado River is in trouble. I think we do we

talk about that last time too? Yeah, I don't remember. Yeah. Okay. It's like 80 there, right? Or 90 or

something, right? Like it's crazy. It's been in the 80s this week. It's it was warm one day here.

It got the 96 last two. Actually, yeah, it was crazy. It's been more seasonal recently. But the

heat dome. The heat dome. Yeah, that's all moved to Duluth. That's supposed to be the the climate

even. Is that or the safe zone? That's what they say. Yeah, well, I guess it's Friday. Any weekend plans?

Uh, now that you mention it, no. I'm like recovering. I was on service last week. I did a bunch of

teaching last week. And it just like, it like warm me out. So this week, I've just been in recovery

mode. And it's been really nice. Went for a hike this morning. Where'd you go? You know, there's

just this nice little hike off the foothills up to it's called like Jack's Peak or Jack's Mountain.

It's great. It's like a thousand feet of elevation over a mile. It's wonderful. Yeah.

I'll be working. So think about me while you're recovering.

Yeah, you've been on for a while. Yeah, I'm on one of our teaching services. And we have half a month

always. So, you know, um, while I'm 15 days or 14, it can be like up to like 16, 17 days,

depending on how the month like falls. My gosh. Yeah. So I'm on 11 of 15. And while I'm just

improving your home life. Pretty much. Yeah. Yeah. Like your wife just like hates you right now.

Is this sustainable? Man, we really don't do that over here anymore. Like we used to do 14s,

but very few people do 14s anymore. We're kind of like sevens and nines of standard. Yeah.

My group kind of just accepts it, but there's always whisperings of like an uprising against it,

but people continue to sign up for it. So yeah, don't change until the people

demand or something. Revolution. Cool. All right. When we talk about some journal articles,

we got a really hot one. We got a big, big landmark paper to talk about. That we do,

Cobra. So let's get into it. I'll talk about Cobra. And then you can provide the expert analysis.

I do just before jumping into the articles that I have not participated in the

last two last week in medicines, but you've done an excellent job. You know, Dr.

Woler's commentary on the PE God minds you and him was very insightful and appreciated. So

anyone who hasn't listened to it, go listen to that. I'm not through the systemosis therapy one,

but you also had an expert on the systemosis therapy with us or with you. And yeah, you know,

I think, I mean, that's awesome, man. Like we're getting really, we've had some true experts on

the pod and that's true. Testament to you and everyone should listen. Oh, thanks, man. No,

those are fun episodes. And right after I finished with the last one, I was like, wait a second.

Is it Dr. Woler or Dr. Waller? And I still don't know. So apologies, Dr. Woler Waller. I don't

know how to say your last name, but I've always thought it was Woler. I think it's Woler, but

maybe we need to go back. Anyway, all right. We were glad to have him. I was glad to listen to him.

Right. He's a gentleman in a scholar. That he is. So on the thrombosis kick, we're going to

talk about the Cobra trial. So this is bleeding risk with a pixaband versus river rocks a band

in acute venous thromboambalism. Cobra stands for comparison of bleeding risk between conveniently

excluded river rocks a band and a pixaband. Pretty cool name. It's great news. Literature might be

catching up with cardiology. Yeah. So Cobra. It was very recently published. I think online first

on the 12th of this month. And then in the New England Journal of Medicine on the 19th of this

month, if I'm not mistaken, by Dr. Castelucci. Castelucci. Still hot. Still hot. Very hot. It's

only the 27th. So yeah, hot off the press and very, you know, very topical as of our late discussions.

So, you know, venous thromboambalic disease is very common. That's the background here. You

know, it's the third most common cause of acute cardiovascular events and CV related deaths worldwide.

We talk about it on our podcast all the time. You know, Dr. Jenkins is a thrombologist. So yeah,

topical and very common. The initial studies for DOACs versus vitamin K antagonist,

have showed lower bleeding rates with the DOACs overall and with a pixaband compared to river

roxaband. But as has multiple retrospective studies that we've talked about previously on

the podcast. So there's always been this signal that sort of favored a pixaband with bleeding.

But these were, you know, these could have been attributed to differences in patient

populations and trial designs. And again, it's been somewhat retrospective or mostly retrospective.

So Cobra is maybe the first or if not the first, one of the only randomized controlled trials

to compare directly compare a pixaband to river roxaband. This is it. This is the only head to head

that I know of. Yeah. Okay. Same, same. I don't know if maybe that, you know, I didn't want to

fully commit to that. But it's the only one we're aware of. So yeah, river rocks or a pixaband versus

river roxaband in acute venous thromboembolic disease. This is a pragmatic international probe trial,

probe spans for prospective randomized open label, blinded endpoint trial, notably not blinded,

you know, on the front end. They did know who was taking what. The included patients were adults

with proximal lower extremity DVT or segmental or more proximal PE. There were some notable

exclusions I thought, you know, you couldn't be on anti-coagulation for greater than 72 hours prior

to enrollment. They did not include advanced kidney disease. So no GFRs of less than 30. They did

not include serotics with child puke class B or C. They didn't include obese patients who were

greater than 120 kilograms. There was no active cancer and they couldn't have another indication

for anti-coagulation. So it's notable that this trial enrollment was going on when some of those

were exclusionary for DOACs. We didn't use to do DOACs and obese patients, but we've done them

with increasing confidence recently. So a few caveats that this may not apply as broadly as we

as we use DOACs now. But anyway, they the the intervention was randomization to standard dose

of pixaband or standard dose river rocksaband and patients were stratified by GFR. So they had,

you know, less than 50 and greater than 50 and ongoing use of anti-platelet medication. Yes,

or no, they were followed for three months. The primary outcome was clinically relevant bleeding

within three months of anti-coagulation initiation, which was a composite of major bleeding or

clinically relevant non-major bleeding. And that was per the international society of thrombosis

in hematology. I think it's worth reviewing that major bleeding is defined as overt bleeding at

a critical site. A decrease of hemoglobin by greater than or equal to two grams per desoliter

requiring a transfusion of greater than or equal to two units of PRBCs or contributed to death.

It's it's any of those, I believe. So if you, you know, you meet major bleeding criteria,

if you hit any of those marks and then clinically relevant non-major bleeding is none of those

things, but has one of these. It resulted in a medical intervention led to hospitalization or

increased level of care or prompted face-to-face evaluation. So it's worth keeping that in mind.

Who are we talking about? Or what's the what are the bleeds that we're talking about? And I think

that does a good job of capturing, you know, who we'd be interested in. I think, you know,

hopefully folks are not presenting for nose bleeds. And I think the signal that we'll talk about

was mostly most notable in the major bleeds, which are the bleeds that we're going to care about

most clinically. So that was the major the major outcome primary outcome, relevant bleeding within

three months. Secondary outcomes had individual components of the primary outcome. They also looked

at recurrent VTE, death from bleeding, death from recurrent venous thromboembolism, death from any

cause and medication adherence. It should be noted that all outcomes were adjudicated by a central

committee that was blinded. You know, they talk about the power detection. They note that,

you know, they would have to, that they assumed a rate of 5.4, a primary outcome event,

rate of 5.4% in the epixaban group and 8.1 in the river rocksaban group, which ended up being,

you know, close to accurate. So they enrolled 2,760 patients from 32 senators across Canada,

Australia and Ireland. Ireland had four patients. There was 1,370 patients randomized to a

pixaban and 1,390 randomized to river rocksaban. It should be noted demographically that only 10%

were non-white when we're talking about Canada and Australia, that kind of tracks. The mean age

was 58.3. Patients looked to be relatively well matched. A few things that I sort of picked out were,

you know, when thinking about these patients and who we're talking about, 77.3% had unprovoked VTE.

52.2% had DVT alone, 47.8% had PE plus or minus DVT and 16% had a history of VTE. So,

you know, I think fairly representative of who we anti-coagulate. They didn't really give us any,

you know, comorbidity data, which was sort of interesting, I thought, you know, how sick were

these folks? What were their comorbidities? What might be their risk for recurrent VTE? That's not

the question, obviously, but still might be sort of helpful to understand a little bit more

about the about the patients, but well matched with the information that we had. So, the primary

outcome occurred in 44 out of 1,345. So, 3.3% of patients in the pixaban group and 96 out of 1,355

or 7.1% in the river rocksaban group. So, 3.3% versus 7.1% that corresponds to a relative risk of

0.46 with a 95% confidence interval of 0.33 to 0.65 and a p-value of less than 0.001. So,

statistically significant better for a pixaban. Major bleeding, you know, which is one of the

components of the composite occurred in five in the pixaban group. So, that's 0.4% versus 32

or 2.4% in the river rocksaban group. So, 5 versus 32 grossly, which correspond to a relative

risk of 0.16 with a confidence interval of 0.06 to 0.4. Again, that's a secondary outcome, but I

thought worth highlighting. They do talk about, you know, they give some specific specifics about

these bleeds. They say, you know, there was a decreased hemoglobin level or transfusion in all

five of the pixaban major bleeders and 28 of the river rocksaban bleeders and then of the other

four river rocksaban bleeders, they had bleeding in a critical area. So, again, you know, this is these

are these are real bleeds for sure. You know, again, within that, within the secondary outcomes,

the non-major, the clinically relevant non-major bleeding was 2.9% versus 4.9% and then recurrent

symptomatic VTE occurred in 1.1% versus 1.0% in the pixaban versus river rocksaban group. So,

relative risk there of 1.08 confidence interval crossed one, one death in the pixaban group,

four death in the river rocksaban group, notably adherence was only 65.7% in the pixaban group

and 75.1% in the river rocksaban group. It could be because river rocksaban after the load is

dose daily and the serious adverse events in both groups were pretty much the same. So, you know,

the authors here conclude that a pixaban is superior to river rocksaban when looking at, you know,

clinically relevant bleeding in the first three months following initiation of anticoagulation

for an acute venous thromboembolic event. And I think it's a well-designed trial. I think it's

a good question to ask. It's the first of its type and we're big a pixaban guys here already,

but this is another feather in a pixaban's cap and I will not, you know, I will continue to

preferentially choose a pixaban moving forward. I think there's a couple, you know, discussion

points about why this happened, but yeah, what were your two cents here, Dr. James?

Another win for a pixaban. What a relief. I would have been really, really shaken if a pixaban

lost. But yeah, it's so nice to have this head-to-head study and I think I never, I didn't really know

if it would ever happen to be honest. I just assumed that these drug companies would never want to

really have that kind of a trial. So did you mention, I don't actually know who funded this trial?

I did not mention that, but it was mostly, it was not industry. It was like mostly the health,

you know, the health ministries of Australia and Canada. Thank you to the Commonwealth

for supplying the funds to answer this important question. Because yeah, like, you know,

the immediate question is like, is river oxaban done, you know, as a toast? And probably not, right?

I think they've been studying river oxaban in lots of different disease processes. This is

specifically looking at VTE, but you know, we still use it for atrial fibrillation and they also

have an indication for peripheral arterial disease and they're always trying it out in other

things and it often doesn't pan out. But, you know, there are indications for river oxaban

outside of VTE. Or you mentioned that there's like some, you know, theories about why river oxaban

has a higher bleeding risk. And I think, you know, one of the biggest reasons probably is that

a pixaban, you only do the high dose treatment for a week and river oxaban, you do it for three

weeks. And I don't know if anybody knows why we do it that way, except that's how it was done

in the original trials. And so that's what the package insert says. You're supposed to do,

but you're probably not getting a lot of like PTE treatment benefit after that first week,

but you are exposing them to higher bleeding risk. And I think if you look at the Kaplan-Mire curve,

like, it splits immediately. And I think it's because of that first three weeks when you have higher

higher dose of river oxaban. So I don't know, like, maybe it's worth going back to the drawing

board and saying, like, couldn't we get away with just one week of high dose of

veroxaban? Do we really have to do this three-week thing and we could maybe have a lower bleeding

risk? But even outside of that, you know, that the 20 milligram dose of river oxaban is key to

give you higher drug levels than a pixaban five, right? And so even after those first three weeks,

you're still exposed to more drug with river oxaban. And so, you know, there's that component to it.

I think the reassuring thing here is that there were no fatal bleeding events in either group.

There was no intracranial bleeding in either group. So that's a relief. So I mean, I think like,

even though a pixaban is clearly better than river oxaban, river oxaban is still like overall

pretty safe. We've been using it for a while. And it's very good at preventing VTE. And so,

yeah, I'm still going to pick a pixaban if that's my choice. But sometimes the insurance company

likes river oxaban. And that's okay. Like, I think it still works pretty well. It did seem like most

of the major bleeding was like vaginal bleeding, some GI bleeding. And those are very important

bleeding events that we should monitor for. And I think if you have a patient who's having a

lot of vaginal bleeding, those are patients that will usually try to get off river oxaban anyway.

And switch them to a pixaban. And I think the study supports that. So, yeah.

Yeah, yeah. I think you brought up the other main points that folks have been discussing,

the dosing issue. It makes too much sense to re-look at the dosing and just do a week load.

Like, that's not going to happen, right? I mean, I guess they'd have to do the whole phase two or

three again. Like, that just seems the drug company's not going to want to bite that bullet.

But yeah, I think the dosing issues are reasonable. Yeah, noting where the bleeding occurred

is also a very good point. The adherence stuff was interesting to me too. I don't normally

think of BID as being that difficult. And in my mind, I always throw around numbers of how,

if you take all the INRs of everyone on Whiffer and what percentage will be therapeutic. And I've

heard 60% thrown around. And I'm like, well, a pixaban is way better than that. People take

their medicines, right? But not really. And like, yeah, 65% is low. And it was interesting in

sort of just a side point. But yeah, I think you're right. I'll continue to prefer a pixaban as we

have discussed previously and do already. But river oxibans probably still fine. And yeah, they weren't

luckily the worst of the bleeds. So do act still, you know, preferred. But if you have the choice

of pixaban. And again, you know, this only applies to acute VTE. We're not talking about long term

or indefinite treatment. We're not talking about atrial fibrillation. Those have not been studied,

although maybe you could extrapolate, you know, I think you could extrapolate some of the retrospective

bleeding stuff to everyone. But yeah, I think another, another win, like you said. Yeah. Yeah.

I think about. Yeah. Cobras such a great name. I guess the other, the other thing I guess we

should mention, you just kind of mentioned it was the long term treatment. So the Renault trial,

you know, you could be on a pixaban or a veroxaban and you just went to the half dose after six

months. And like there wasn't like a signal there for increased bleeding with river oxaban compared

to a pixaban. And so I think like when you're in that space, when you're doing the prophylactic dose,

it probably doesn't matter. You could use either one. And so if you have a patient who is struggling

with the twice a day dosing of a pixaban, river oxaban, 10 milligrams, you know, the Renault trial

showed that it was really good at preventing VTE events and the bleeding rates were similar. And so

so I think that's okay. It's really just this acute treatment phase. Like you mentioned where

you see that huge reduction in bleeding. Cool. Should we do the other paper? Yeah. Mine's not as

exciting as yours. But I looked at it as an opportunity to learn about something that I generally

try to avoid. And yeah, usually so this was the the closure AF trials that when I want to talk

about the journal articles called left atrial appendage closure or medical therapy and atrial

fibrillation. And I often don't follow these device trials very closely because I'm like not the

guy who's going to do the procedure. So I'm like, whatever. But I thought this one was interesting.

And I think worth worth discussion because it does get to some of these same questions about

bleeding risk and and in our but this is in patients with atrial fibrillation. So these

devices have been around for a bit now. Watchman was I think first published in 2014 in the

Protect AF and study these are percutaneous devices that you can go in and close the left atrial

appendage. The theory being that that's where most the clots are that cause strokes in atrial

fibrillation. So if we can just you know close that off, then we're going to prevent strokes.

And we could do it in patients who have a high bleeding risk and can't be on long-term oral

anticoagulation. And so the first trial was Protect AF that was back in 2014 700 patients.

And that was Watchman versus Warfarin. And they did show that this device was not inferior

for their composite outcome of stroke. Systemic embolism and cardiovascular death and actually

Watchman was superior to Warfarin for a cardiovascular mortality and all cause mortality, which

is kind of a surprising result. But they had lots of parry procedural complications. And that's always

the trade-off with these devices is you are putting a foreign body into a very high risk

or real estate area, right? So they had about 5% of patients who got a Watchman had a serious

you know procedural or 6% had a serious procedural event, including paracardiophusions,

ischemic stroke or device embolization. That was followed up by a smaller study that prevailed trial

also in 2014. And in that one, Watchman did not meet non-inferiority compared to Warfarin,

but they had very low event rates in both. And then fast forward to 2020, we had the Prague

17 study that was 400 high risk patients and they could use Watchman or the Amulet device.

And they found that it was not inferior to DOAX for a composite endpoint that included

cardio-involved events, cardiovascular death, clinically relevant bleeding and device

procedure complications. So kind of taking all of the bad things that could happen to these

patients and lumping it all into one composite outcome. And so in that scenario, it was not inferior.

Based on that in earlier studies, the A-5 guidelines in 2023 did give a class to

A recommendation that in patients with A-5 and moderate to high risk of stroke and a

contraindication to long-term anticoagulation that was due to a non-reversible cause,

it was reasonable to do a percutaneous left-atrial appendage occlusion. They had a class

to B recommendation that you could do it in patients with A-5 and moderate to high risk of stroke

who had a high risk of major bleeding on oral anticoagulation. So not like an absolute contraindication,

but they had a high bleeding risk. And so people have been doing this procedure. And we had another

follow-up trial in 2024, the option study. This was specifically looking at patients who were

getting an ablation for A-5. They said if we also did left-atrial occlusion, how would that work?

They had 1,600 patients. And it was not inferior in that study to oral anticoagulation for death

stroke and systemic embolism. And they showed a reduction in clinically relevant bleeding.

So I think people are getting more and more comfortable with this. And so that's why I think this

new paper is interesting. So the Closure AF study was published March 18th, 2026 in the New England

Journal. First author was Dr. Ulf Landmesser. And this study was done in Germany and lots of

centers, 42 centers. And they enrolled close to 900 patients, ended up being 888. And they randomized

them one to one to left-atrial appendage occlusion or usual care under the guidance of a physician.

And ultimately, 94% of the patients randomized to the device arm did get the procedure. So that

was pretty good. Looking at the patients in table one, they were old. So about 78 years old was

the average, which was six years older than the patients in that Prague 17 trial. They were mostly

men. 94% white. And this is Germany we're talking about. The average Chad's vast score was 5.2.

So very high risk for stroke. Average has blood score was three. So high risk of bleeding as well.

Who knows what to do with the has blood score, but it's what we got. And looking at their past

history, 42% of them had some kind of major bleeding in the past. So these are high bleeding

risk patients. And so the primary endpoint that they used was similar to Prague. It was this

composite of stroke, systemic embolism, major bleeding, cardiovascular death. And so kind of all

of the bad things that could happen assessed in a time to event analysis. And what they found was

that the primary endpoint occurred in 16.8 events per 100 patient years in the device group and

13.3 in the medical therapy group. And so it did not meet their non inferiority margin, which was

the hazard ratio of 1.3. They had more strokes, or sorry, no, same amount of strokes in both groups,

27 patients in both groups. But they actually had more bleeding in the device group, which is kind

of surprising when you're comparing it to oral anticoagulation. We have to remember that when you

put these devices in, they usually keep them on dual anti-platelet therapy for like six months,

I believe, after the procedure. And then they'll like downgrade to like aspirin usually after that.

And so they're usually on some kind of medicine that could cause bleeding. And so these patients,

23 of them in the procedure arm, did have like a major paraprecedural bleed, including five cases

of cardiac tamponod. There were also more deaths in the device group, 155 versus 141 in the medical

therapy group. And overall paraprecedural complication rate of about 5.7%, which is very similar to

the original Protect AF study around that number. So I think it's interesting to have a trial like

this come out after people have become more and more comfortable with this left-atrial occlusion

device. I think this should give us pause that maybe the data is not super clear on the benefits

of this device. And there's clearly a risk associated with this, especially paraprecedural risk.

Interestingly, I noticed that there's a big trial that's going to be presented tomorrow at the American

College of Cardiology conference in New Orleans. It's the champion AF trial. And this was looking

at the watchman in like pretty much all comers with AFib. So like low bleeding risk patients

included. So low moderate and high. And they enrolled like 3,000 patients. So I'm very curious

what that trial is going to show. And we'll probably have to do an update once that actually gets

published. But for me, this new closure AF trial does give me pause because I think we have

these patients, these scenarios where they just keep bleeding. They don't tolerate anticoagulation,

but they have that high stroke risk. And you want that watchman to be a reasonable alternative.

And I just don't know. I guess a lot of it is still going to come down to share decision-making

and patient preference. And you know, if they want to go for it, then I think it's an option

on the table, but they need to know that there are pretty significant risks.

Yeah, yeah, I agree. I think that was a great analysis. Steven, thanks. I feel the same way

in that I don't think about this. You know, we, whatever, hold the anticoagulation when the

patient's bleeding and send them away and say, consider watchman or, you know, whatever, you know,

left-atrial appendage closure. So thinking about it is good and is important. And I'm glad that

we're talking about this. You know, I think the cardiologists or the folks who perform these

interventions are going to say, some operator dependent, I don't have this level of peri-procedural

bleeding. You know, I think you hit the nail on the head that the bleeding being the same in both

groups is unexpected. But, you know, it's a procedure issue or it's a patient selection issue.

You know, I think, yeah, you mentioned something like 45 percent had a history of major bleeding

and then presumably the other 50-some odd plus are just an elevated hazblood, which like, you know,

yeah, like you said is we, I don't know exactly what to do with that. Like until someone's proven

that they've, that they can't tolerate anticoagulation with a Chad's Vask of five, maybe, maybe that's

not quite the right person to pick for the watchman right now. But yeah, maybe champion will tell

us something different. So I think they'd say that that's, that would be their retorts and maybe

valid, maybe not. But yeah, I think the, the data here is definitely cause for, for pause, you know,

pardon my rhyme. You know, the, in the discussion, they still do note that left-atrial appendage closure

did reduce stroke risk below what would be expected for a Chad's Vask of five. So it like, did

what you, what you wanted it to from that standpoint. But then yeah, if you compare it to just

taking a pill, it's, it's not not inferior and, you know, signal towards sort of worse. That's not

what they were looking at. But, you know, the composite, or the primary outcome was worse for them.

So yeah, I, I think it's good to think about, I don't know what the cardiac, what the cardiologist will

say, you know, the commentary here was like the associated commentary in the journal. I thought

was, was very poignant in that it just said we should slow down and this should not go the way

of like renal denervation or, you know, PCI for CTO, things that don't have a lot of data for them

that we do and that maybe get ahead of us. So, you know, caution is warranted. I would agree,

I would agree with that. Yeah, yeah. Well said. Yeah, maybe they're just bad at this procedure in

Germany. Those Germans, I don't know what they're doing. I mean, you know, does the device matter to,

you know, some watchman, some amulet, some whatever, something else? Well, and so yeah, and there is

this other population where they've studied where if you're undergoing cardiac surgery,

you can have your left atrial appendage included in surgery, like surgically included, right?

Like basically ligated. And those patients do better. There's a class one recommendation if you're

getting cardiac surgery, you might as well have this done while you're under, because it does

reduce stroke risk, but that's in patients who continue to take anicoagulation. So it's not like

in place of oral anicoagulation. It's just an addition to will further reduce your stroke risk.

And it's uncertain whether those patients can stop taking anicoagulation after. So yeah, it's

interesting. You know, we developed these really cool procedures, devices, techniques, and sometimes

the bar is very low to actually get them to patients. So like that's why, you know, I'm cautious on

all of these things, because until you show me that it actually improves patient centered outcomes,

you know, we know it can improve someone's bank account, but what we really need to know is,

does it help the patients? And so that's why, you know, I've been like a little bit of a skeptic on

advanced therapies for pulmonary embolism, because I'm like, just because you can suck a clot out

of someone doesn't mean you helped them. It's really cool, though. I do like the pictures when they

show all the clots, you know, on the blue clots. Yeah, and it's like, well, look at this clot that

I got out of this guy. It's like showing off a fish that you caught. It is really cool. But like,

does it actually help the patient? We'll find out maybe this year there's some big PE trials that

are going to get published. And you know, we'll see. I hope I'm wrong. I hope it really is helpful.

Stay tuned. Yeah, cool. Well, this was a great episode. Thanks, Dr. Rupp.

Yeah, who knows when we'll be back, but hopefully soon. Yeah, we are coming up on the summer,

which is kind of a dead time. It's usually when we die. That's usually when we put the podcast

back on life support. But we're always there, you know, we're always, we're never, we're never fully DNR.

We're just like on ECMO. That's right. That's right. All right, man. Good talk. Good chat.

Get you later. See you, man. All right, bye.