The PEERLESS Trial: What Are the Implications for the Management of Pulmonary Embolism?

An Interview With Ripal Gandhi, MD

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VASCULAR DISEASE MANAGEMENT. 2025;22(3):E18-E19 

At ISET 2025, interventional radiologist Ripal Gandhi, MD, from Baptist Health Miami Cardiac & Vascular Institute and Miami Cancer Institute, gave a presentation entitled “PEERLESS Trial: Implications for Management of Pulmonary Embolism”. Vascular Disease Management spoke with Dr Gandhi about the PEERLESS trial, a prospective, multicenter, randomized controlled trial (RCT) that enrolled 550 patients with pulmonary embolism (PE) and compared treatment with mechanical thrombectomy (FlowTriever, Inari Medical) and catheter-directed thrombolysis (CDT).

The PEERLESS trial is the first RCT evaluating FlowTriever and the first major RCT on PE in nearly a decade. What motivated the decision to compare FlowTriever against CDT, and how does this study address the limitations of previous trials?

There are 2 main interventional therapies for PE: mechanical thrombectomy and CDT. We have been doing both of these interventions for many years. But when we have a patient with intermediate-risk PE who requires an intervention, we don't know which intervention is better. There are no comparative studies. All of the studies look at one device or another, but there is nothing comparing the two. This is the first study to do so. It made a lot of sense—here is a patient that we are going to intervene upon, that decision is already made. Now, which intervention is actually better? 

The primary endpoint was based on a win ratio looking at 5 different criteria: mortality, intracranial hemorrhage, major bleeding, clinical deterioration and bailout, and ICU admission and length of stay. 

Can you elaborate on how the win ratio methodology influenced the interpretation of the results, and were there any surprising findings?

A win ratio is being increasingly utilized in a lot of clinical trials, including cardiovascular trials, and it allows us to take different outcomes and rank them per their clinical importance in a hierarchical manner. You are putting the most important factors first, and then you are going down to the less important ones. A ratio of 5.01 was positive, making the study both statistically and clinically significant. If you look at other trials that have been done in this space recently, you could have a win ratio much lower than that, which is still considered positive, but this is an overwhelmingly positive trial. 

Let’s delve into the 5 components of the win ratio utilized in this study. All-cause mortality was equivalent between the 2 arms. I am not surprised by that finding given the risk of mortality is relatively low in intermediate-risk PE patients, and the study was not powered to assess difference in mortality. One of the surprising findings, at least on the surface, was that risk of intracranial and major bleeding was equivalent in the 2 groups. This is where the details of the study population are relevant—only 4% of patients actually had a contraindication of thrombolytics in both arms. That's not what you see in the real world. When we were enrolling patients, if they had any risk factor that might put them at increased risk of bleeding, we didn't enroll them in the study and placed those patients in a nonrandomized cohort arm, which is still being analyzed. What we can conclude from the study is that in a low-risk-for-bleeding population, the bleeding risk is equivalent. The 2 factors that were positive were clinical deterioration and/or bailout, which was markedly improved with the FlowTriever. There were 3 times more clinical deteriorations/bailouts with CDT. ICU admission and length of stay were also significantly greater with CDT.

Given the PEERLESS trial results, how do you foresee the impact on current PE treatment guidelines? 

We have done a lot of trials showing the safety and effectiveness of utilizing catheter-based interventions for intermediate-risk PE, and we are seeing very low mortality, very low bleeding risk, and very low complications. But what we have not done yet is a definitive trial comparing catheter-based therapy vs anticoagulation, which is still considered the standard of care for intermediate-risk PE. In order to really change the guidelines, we need a randomized clinical trial comparing large bore mechanical thrombectomy vs anticoagulation alone.

And that study is being done—that’s the PEERLESS II trial, which is currently enrolling. There are other trials that are evaluating the same thing, including PE-TRACT, STORM-PE and HI-PEITHO. Until we see positive trials of endovascular intervention compared to anticoagulation, I don't think we are going to see a change in the guidelines.

What key questions are you hoping to answer with the PEERLESS II trial? 

In general, we are trying to answer this question: For patients with intermediate-risk PE, is a catheter-based intervention, specifically with large bore mechanical thrombectomy with the FlowTriever, superior to anticoagulation alone? This is the largest RCT that is being done in this space, with 1200 patients. The primary endpoint also, based on the win ratio, is looking at all-cause mortality at 30 days, clinical deterioration, all-cause hospital readmission by 30 days, bailout therapy, and dyspnea at 48 hours. That is a legitimate trial with legitimate endpoints. If it’s positive, it will change the guidelines. 

When will we see the results of that trial? 

It is currently enrolling, so it is going to be a while.

I understand that you are presenting a featured abstract of data that have not been presented regarding clinical deterioration and escalation in the PEERLESS trial. Can you tell us about the data?

We were one of the major enrolling sites in the PEERLESS trial, so I am fortunate to be able to present the data at ISET this year. What we are specifically looking at are the PEERLESS results and looking at the characteristics and the timing of clinical deterioration and bailout therapy that were observed in the PEERLESS trial and why that might have occurred. As an overall summary, there were 3 times more clinical deteriorations and/or bailouts in the CDT arm vs the FlowTriever thrombectomy arm. What I will be presenting is that number one, clinical deterioration events were much more severe in the CDT arm, and number two, not only was there a difference in severity, but there was a difference in the timing of the events. All the deteriorations occurred at the time of the procedure with thrombectomy, which is what I want as an interventionalist. If there are issues with the patient in terms of clinical deterioration, I want these to occur during the procedure on the table where I can fix it. The timing for clinical deterioration in the CDT arm was 2 to 3 days after the intervention. There was 1 patient who had a deterioration 6 days after the CDT intervention, and that is not what we want. I would rather have it at the time of the intervention. 

Why are we seeing fewer and less severe clinical deteriorations with large bore mechanical thrombectomy? The patients treated with thrombectomy had better recovery in respiratory rate, symptom scores, and right ventricular function at 24 hours, suggesting a physiological rationale for the lower rate of deterioration and/or bailout observed in this group. n