I have written fairly extensively about the management of high risk PE. Despite their growing popularity, I have remained quite skeptical of catheter directed therapies. If you are going to give a thrombolytic, my sense is that it is going to be just as effective if given through a peripheral vein, and that fancy catheters add nothing but risk and cost. Of course, that impression is based on pretty weak evidence, so I am always looking for new trials to update my opinion. Today we have 2 new PE trials: the STORM-PE and STRATIFY trials.
STORM-PE
Lookstein RA, Konstantinides SV, Weinberg I, Dohad SY, Rosol Z, Kopeć G, Moriarty JM, Parikh SA, Holden A, Channick RN, McDonald B, Nagarsheth KH, Yamada K, Rosovsky RP; STORM-PE Trial Investigators. Randomized Controlled Trial of Mechanical Thrombectomy With Anticoagulation Versus Anticoagulation Alone for Acute Intermediate-High Risk Pulmonary Embolism: Primary Outcomes From the STORM-PE Trial. Circulation. 2026 Jan 6;153(1):21-34. doi: 10.1161/CIRCULATIONAHA.125.077232. Epub 2025 Nov 3. PMID: 41183181
Methods
The STORM-PE trial is an international multicenter open-label RCT. It included adult patients with normal blood pressure and intermediate-high risk PE (which basically just meant an elevated troponin, BNP, or large RV on imaging). All patients were treated with heparin, and they were randomized to either get a “computer-assisted vacuum thrombectomy” or nothing. This “CAVT” is a novel form of mechanical thrombectomy that uses some kind of proprietary software algorithm to aspirate clot while minimizing blood loss.
Results
They enrolled 100 patients (of 767 screened). There was a statistical difference in their primary outcome, which was mean reduction of the RV/LV ratio at 48 hours.
They report no differences in adjudicated adverse events. (I feel like adjudication just adds bias in an unblinded trial).
Clinical deterioration requiring rescue therapy occurred in 1 patient in the thrombectomy group and 3 in the standard care group.
There were only 2 deaths, and both occurred in the thrombectomy group.
They report less tachycardia at 48 hours in the thrombectomy group, although that group was also more tachycardic to begin with, so there was no difference in the change in heart rate. Either way, the difference is almost certainly clinically meaningless (heart rate of 87 vs 80).
There were no recurrent PEs in either group.
My thoughts
If it hadn’t been sent to me for my thoughts, I would have ignored this paper. The RV/LV ratio is clearly not a patient oriented outcome. It is not an outcome that should ever drive clinical practice. This is the kind of research that needs to be done to determine whether there is justification for a larger RCT looking at clinical outcomes, but this is not the kind of trial that clinicians should pay attention to. At this point, with no evidence of patient oriented or clinical benefit, no one should be using this device outside of a clinical trial.
You can’t really make anything out of the ‘clinical deterioration requiring therapy’ secondary outcome. This is an unblinded trial, and you aren’t going to take a patient who just had a thrombectomy back for thrombectomy, but you will clearly have a lower bar to escalate the patients who have not yet had an intervention.
Although clearly not statistically significant, it is concerning to me that there were infinitely more deaths in the thrombectomy group (2 vs 0).
Perhaps the biggest issue with this trial was the target population. These are not the patients I would be targeting. I don’t think that troponin or BNP, in an otherwise well patient, means anything. These patients generally have fantastic outcomes, and so subjecting them to an invasive procedure makes no sense. They excluded anyone with any hint of hemodynamic instability, which is the group of patients where these interventions actually make sense. The fact that there were 0 deaths in the control group basically proves that the intervention could not possibly help this population.
Finally, this trial design could never answer the question of whether this specific “computer assisted” device provides any value. That makes sense, given that the sponsor was “involved in the study design, data collection, analysis, and interpretation, manuscript preparation, and the decision to publish.” Without a standard catheter device as a comparison group, there is no way to know whether this fancy device is better or worse. Based on the other studies I have seen, there is absolutely nothing to say that the computer algorithm added anything here, aside from cost. Allowing manufacturers to design their own trials is clearly dumb, and results in trial designs that can only act as advertisements rather than helpful science.
Conclusion
This is basically a pilot trial, looking at disease oriented rather than patient oriented outcomes. It is an unblinded trial, designed and run by the device manufacturer. Even with those biases, the results are completely underwhelming. No one should be using this device at this time.
STRATIFY
Kjaergaard J, Bang LE, Sonne-Holm E, Wiberg S, Holmvang L, Lassen JF, Sørensen R, Høfsten DE, Ulriksen PS, Jawad S, Palm P, Søe C, Ersbøll MK, Boesgaard S, Møller JE, Thune JJ, Hassager C, Tilsted HH, Lønborg J, Egstrup M, Kristiansen OP, Seven E, Lindholm MG, Eskesen K, Fanø S, Carlsen J. Randomized trial of low-dose -, ultrasound assisted thrombolysis or heparin for pulmonary embolism. Cardiovasc Res. 2026 Jan 29:cvag038. doi: 10.1093/cvr/cvag038. PMID: 41610160
Methods
The STRATIFY trial is an open label multicentre RCT that randomized adult patients with acute intermediate high-risk PE according to ECS guidelines (basically RV dilatation and elevated troponin) to one of three groups: heparin alone, heparin plus ultrasound assisted thrombolysis using 20mg of alteplase over 6 hours, or heparin plus intravenous alteplase (also 20mg over 6 hours).
Results
They included 210 patients (out of 673 screened), and the groups look relatively similar at baseline.
Unfortunately, like the prior study, their primary outcome was disease oriented: change in thrombus burden. There was a statistical improvement in the thrombus burden using a refined modified Miller score with both thrombolysis groups as compared to heparin alone, but there was no benefit of using ultrasound assisted thrombolysis as compared to just giving the dose through the peripheral IV. (Reduction in the score of 6.3 vs 6.1 vs 2.6).
At 3 months, mortality was 4.3% with thrombolysis and 0% with heparin, but not statistically different. They give us causes of death for 5 patients, and at least 3 of the 5 were bleeding related (1 GI bleeds and 2 intracranial hemorrhages).
Bleeding was higher, but not statistically so, with thrombolysis (11% vs 4%).
There were no differences in the quality of life or walk test measurements at 3 months.
My thoughts
I was excited to see this study, because most of the studies I have seen listed on clinicaltrials.gov seem to assume that a catheter is beneficial, and so only compare catheter directed thrombolysis to heparin (leaving out the intravenous thrombolysis arm). Others compare to intravenous thrombolytics, but use wildly different doses of thrombolytics, which just doesn’t make sense. This trial, using the same low and slow dose of alteplase both intravenously and through the pulmonary artery catheter is clearly the way to go, and seems to support my contention that there is absolutely no value from these catheters. If you are going to give thrombolytics, you should just give them though an IV.
Of course, this trial makes thrombolysis look bad, in my opinion. They sort of skirt over that fact, by focusing on disease oriented outcomes. However, thrombolysis did not seem to improve anything important, but seemed to result in more bleeding and more death. Not something I would choose.
As far as the disease oriented outcome is concerned, I don’t really know what changes in this score mean. It is funny that the Miller score needed to be both modified and refined. I am not familiar with this score, but I really question the validity of any score that required multiple modifications. Furthermore, I do not know what change in this score would be considered clinically important, and AI models like OpenEvidence have never even heard of the refined modified version of this score, and tell me that for the basic Miller Index no minimal clinically important difference has been established.
Like the last trial, I think they are focused on the wrong population. Troponin elevations simply catch too broad a group of patients, and RV dilatation is also not specific enough. If we are going to find a benefit, patients are going to have to be sicker. The 0% mortality in the control group sort of proves that thrombolysis was never going to helpful. I don’t think we need to wait until patients are peri-arrest, but we are going to need to find different hemodynamic criteria to identify patients who actually have a risk of dying from their PE if we are going to see any benefit from thrombolysis.
That being said, I think this approach – a low and slow dose of thrombolysis through a peripheral IV – is clearly going to be the best approach going forward. No one should be using fancy, expensive, invasive catheters until they have been proven to provide a benefit over the exact same dose of thrombolytic given through a peripheral IV. (Given that the entire blood circulation goes through the pulmonary arteries, I cannot imagine that the catheters provide any value, except to shareholders in these companies.)
Conclusion
If you are going to use thrombolysis, you should provide it through a peripheral IV, not a specialized catheter. That being said, the results don’t look good in this study, and I definitely would not be giving it in this specific population.
Overall conclusion
I don’t think either of these trials significantly changes our management of pulmonary embolism patients. In sick (hypotensive) patients, thrombolysis is a good idea. Outside of that, we are still trying to define the right population for more aggressive therapy. To date, there is absolutely no evidence that fancy devices or thrombectomy are a good idea. In the long run, based on their value in other conditions, I could imagine thrombectomy being effective, but there is about 0% chance that catheter directed thrombolysis will be more effective that systemic thrombolysis.
Morgenstern, J. Higher risk PE management updates (The STRATIFY and STORM-PE trials), First10EM, April 13, 2026. Available at:
https://doi.org/10.51684/FIRS.145360
Other FOAMed
Management of intermediate and high risk pulmonary embolism (aka submassive/massive PE)
PulmCrit: Catheter-directed lysis = Peripheral lysis for PE (STRATIFY trial!)
EM Cases Ep 203 Intermediate Risk Pulmonary Embolism Risk Stratification, Management and Algorithm
6 thoughts on “Higher risk PE management updates (The STRATIFY and STORM-PE trials)”
With respect to the first study commentary, I think there is sufficient evidence that those with “right heart strain” after acute PE are at increased risk for persistent RV dysfunction. I don’t have some of these definitions handy (e.g. right heart strain is probably ECHO, trop or BNP markers at time of PE, and “RV dysfunction is either symptoms correlated with ECHO or simply just ECHO). (Wang et al 2023 meta-analysis looked at both imaging and functional assessments via NYHA classification). So I don’t think the target population is all that bad in the first study. We suspect that thrombolysis or thrombectomy after a massive PE who is about to die is probably a good idea (again I don’t know the studies but if someone is on two pressors and intubated after acute PE, I’d strongly favor thromboylsis or thrombectomy if the data said it worked), but we have this intermediate population where we are trying to determine if we should do anything more than just anticoagulation for those stable vital sign patients with RV strain.
Thanks for the comment.
Although RV strain might be associated with longer term dysfunction, the long term evidence so far show absolutely no benefit in treating the RV strain. The only purported benefit so far is a mortality benefit, not a benefit in terms of long term functional outcomes. (That is what the PEITHO trial attempted to look at, and showed no benefit.) So when these trials use RV strain as their surrogate outcome, they are using it as a marker of short term bad outcomes – aka mortality. Although this is one of the big issues with surrogate outcomes – who knows what they mean? If they were really worried about long term outcomes, though, they would have to design a very different trial.
I agree that we are searching for the right population for treatment. However, you go too extreme in your examples. Right now, any hypotension is an indication for thrombolysis. You don’t need to go so extreme as to be requiring 2 vasopressors. But if lytics are going to help, the benefit is almost certainty going to be a mortality benefit (especially after PEITHO showed no functional benefits). If that is true, the study group have to have some chance of dying. That doesn’t mean you need to focus on ICU patients on 2 pressors who are you pretty sure are going to die. But it means you need to find higher risk criteria. In this study, the control group had 0 deaths. You cannot improve on that. How could the benefits of an invasive procedure or thrombolytics possibly outweigh harms when you are starting with a group that had 0 bad outcomes?
Although there is still theoretically a chance of long term benefit after PEITHO, you certainty can’t use a surrogate outcome to infer any kind of long term outcome. We already have enough studies to show these interventions change disease oriented outcomes. What we need are studies that show patient oriented outcomes. Designing trials to look at RV strain at this point is either a waste of time, or worse – considering that people will use this data to push forward an agenda of invasive management that has absolutely no evidence of actually helping patients.
I’m just discussing intermediate PE, not massive PE. I use massive PE as an example because we see morbidity and mortality benefit there, so it’s worth testing whether we see a morbidity and mortality benefit in intermediate PE. Even though STORM-PE trial showed no mortality, there is objectively near term death from intermediate PE and the N wasn’t high enough, only 100 patients. There were deaths in both null and treatment PEITHO groups after 7 days, which had 10x patients.
(Yes I agree that we can’t improve on death if nobody died. Maybe one of the trials would have “negative death” LOL The intervention group started with n=1000, there were -5 deaths, and the trial ended with 1005 patients. *tongue in cheek*)
I was unaware of the PEITHO trial, which seems like a good study. The **PEITHO (Pulmonary Embolism International Thrombolysis) trial** was the largest randomized controlled trial of systemic thrombolysis in intermediate-risk pulmonary embolism, enrolling 1,006 patients across Europe.[1] The trial compared a single intravenous bolus of **tenecteplase plus heparin** versus **placebo plus heparin** in normotensive patients with confirmed PE, right ventricular dysfunction on imaging, and elevated cardiac troponin levels.[2] The trial demonstrated there was no significant difference in overall mortality at 7 days (2.4% vs 3.2%, P=0.42).
Long-term follow-up of 709 patients (median 37.8 months) revealed **no difference in mortality** (20.3% vs 18.0%, P=0.43), persistent dyspnea or functional limitation (36.0% vs 30.1%, P=0.23), or chronic thromboembolic pulmonary hypertension (2.1% vs 3.2%, P=0.79).
It’s a good post. We are supposed to activate the “PE pager” at my hospital for massive and submassive PE because many of them are taken to the cath lab for thrombectomy (I know this post was about thrombolysis though, but still the framework is there to alert everyone for a submassive PE).
Yeah – these PE teams have really got ahead of the evidence
At this point, I don’t think there is any difference between thrombolysis and thrombectomy (and we don’t know whether either is better than just heparin). My bet is that they will help the right population, but we still need to figure out who that is.
I think you make my point though – a small trial with a surrogate outcome was never going to show anything of value. The critical appraisal was obvious before the trial started, and there was no way this trial as designed was going to result in data that actually improves patient care. We need bigger trials focused on patient centered outcomes.
But I also think their choice of population was problematic. “Intermediate risk” or “submassive” PE is a massive heterogenous group of patients. Identifying a group with 0 mortality means you are identifying a group with basically 0 chance of benefiting from the intervention. Maybe people would have died if the trial was larger, but I think not, based on their exclusion criteria. If a patient isn’t at least moderately tachycardiac, or has some other important clinical marker of hemodynamic consequence, why the heck are we even considering these advanced therapies?
Thrombolysis in high-risk intermediate PE seems a wild-goose chase.
Fortunately, with anticoagulation and other standard measures leads to such a good prognosis that chasing the right sick population could be futile.
Maybe, the right population is…just high risk PE?…
I don’t know. There are multiple meta-analyses showing decreased mortality with thrombolysis in submassive PE.
https://first10em.com/management-of-intermediate-and-high-risk-pulmonary-embolism/
No study is definitive, but I think the signal is there. My bet is there is a population where lysis will provide a net benefit, and we need to find that population. Unfortunately, the current wave of research seems more focused on proprietary fancy invasive devices, rather than basic intravenous thrombolysis, which should almost certainly be established as effective first, and is likely to be as good as any of the invasive catheters.