Thrombectomy for DVT: Tips on Patient Selection and Procedure

The questions of when and how to employ thrombectomy for deep vein thrombosis (DVT) were addressed this afternoon by Kush Desai, Associate Professor of Radiology, Surgery and Medicine at Northwestern University Feinberg School of Medicine, Illinois, USA. During a VIVA@LINC session, Professor Desai discussed the issue of patient selection, shared his insights on procedural nuances, and illustrated his preferred approach with case studies. He spoke to LINC Today to give a taste of what covered and to offer his perspective on the research landscape more broadly.

To set the scene, Professor Desai introduced the rationale for considering thrombectomy in DVT. “The long-held standard of care for DVT has been anticoagulation therapy,” he began. “But we’ve seen that half or more of these patients develop some element of post-thrombotic syndrome [PTS], which if severe can be debilitating and limit quality of life. For those cases, the question that we’ve had for many years is: Does removal of the thrombus result in reduction or elimination of PTS?” 

To answer this question, Professor Desai moved on to discuss the research on PTS following endovascular thrombectomy. In his talk, he considered both mechanical thrombectomy, in which a catheter-based device is used to macerate, fragment ,and/or aspirate the thrombus, and pharmacomechanical catheter-directed thrombolysis (PCDT), in which mechanical thrombectomy is combined with the delivery of a fibrinolytic drug into the thrombus via an infusion catheter or wire. Currently, PCDT has a more extensive research base than mechanical thrombectomy without fibrinolytic therapy. 

Discussing this evidence, Professor Desai highlighted the ATTRACT trial, a large multicenter randomized controlled trial (RCT) that enrolled 692 patients with acute proximal DVT. Patients were randomized to receive either anticoagulation therapy alone or anticoagulation therapy plus PCDT (which involved intra-thrombus delivery of recombinant tissue plasminogen activator as well as aspiration or maceration of the thrombus). 

Analysis of the full cohort revealed no significant difference between the groups in the percentage of patients developing PTS between 6 and 24 months of follow-up, or in the improvement in quality of life from baseline to 24 months. PCDT was also associated with more major bleeding events within 10 days (1.7% vs. 0.3%; P=.049).¹

“ATTRACT showed that amongst all comers with acute proximal DVT there wasn’t a benefit of PCDT in terms of PTS reduction,” Professor Desai summarized. “But we learned more from sub-analyses of ATTRACT… since this was a large, robustly designed trial, it was possible to perform many sub-analyses to provide more granular detail. Analysis revealed that in a particular subset of patients, specifically those with acute iliofemoral DVT, there was a benefit in terms of PTS severity reduction.” 

Within the ATTRACT trial, 391 patients were treated for acute DVT involving the iliac and/or common femoral veins. Amongst this cohort, while there was no difference in the occurrence of PTS between the groups, there was a benefit of PCDT in terms of reduced PTS severity (lower mean Villalta and Venous Clinical Severity Scores at 6, 12, 18 and 24 months, P<.01 at all time-points). The PCDT group also showed a greater reduction in leg pain and swelling at both 10 and 30 days (P<.01) and a greater improvement in venous disease-specific quality of life from baseline to 24 months (P=.029). In contrast to the analysis of the whole ATTRACT trial population, no between-group difference was found in the occurrence of major bleeding events within 10 days.²

“Patients with acute iliofemoral DVT who are treated with PCDT develop much less severe PTS than if they had been treated with blood thinners alone,” concluded Professor Desai. “So, in that subset of patients there is a clear role for thrombectomy.”

Describing this subset in more detail, Professor Desai summarized the lessons learned from ATTRACT regarding patient selection. “We would select patients who present with moderate to severe symptoms denoted by a Villalta score of roughly 10 or greater, and have iliofemoral DVT, and have a relatively limited time-onset of symptoms – the cut-off for ATTRACT enrollment was 14 days.”

Professor Desai believes there could be some flexibility regarding this 14-day window, as clot organization is an inflammatory process that will be slower in older patients, but clinical data on this is lacking. “We don’t have clarity on treating older or subacute thrombi from rigorous trials,” he admitted, “but ATTRACT has given us a relatively good insight on when to treat with thrombectomy.”

Having discussed when to treat, Professor Desai moved on to the second part of his talk: how to treat. As regards the different device options available, he highlighted that recent technological innovation has improved safety and efficacy.

“We’ve seen a rapid proliferation of thrombectomy devices with different mechanisms of action, but the unifying achievement is that removal of thrombus has become far more efficient and has remained relatively safe,” he commented. “We are now at the point where the choice of thrombectomy device may be partially operator-based, but we are going to learn more about long-term outcomes with ongoing trials that are specifically evaluating certain devices.”

In particular, Professor Desai referred to the BOLT study, for which he is one of the principal investigators. This prospective trial will assess the safety and efficacy of the Indigo Aspiration System (Penumbra) for percutaneous mechanical thrombectomy in patients with obstruction due to DVT.³ Another ongoing study is the DEFIANCE trial, a prospective multicenter RCT comparing clinical outcomes between patients treated with mechanical thrombectomy (ClotTriever System; Inari Medical) and those treated with anticoagulation therapy alone for symptomatic unilateral iliofemoral DVT.⁴

Further data on the ClotTriever System will be provided by the CLOUT registry, which aims to evaluate real-world patient outcomes when this system is used for treatment of acute, subacute, and chronic proximal lower extremity DVT. Interim data is now available, with 6-month outcomes from the first 250 patients published in 2022. These results are encouraging: the primary effectiveness endpoint (≥75% thrombus removal, as determined by independent core-lab adjudicated Marder scores) was achieved in 86% of limbs, while 24% of patients had PTS; 1 device-related serious adverse event was reported within 30 days. Significant and sustained improvements were reported in all clinical outcomes studied.⁵

In addition to discussing device options, Professor Desai will cover procedural details in his talk, advising on the access site, the role of venography, and when adjunctive treatments such as stent placement are necessary. Touching on this topic, he commented on his approach to stent placement.

“We know that most patients with iliofemoral DVT will have the risk of iliac vein compression or post-thrombotic change in their iliac vein that may have been clinically silent prior to the index DVT event,” he explained, “so it’s important to assess for that during the thrombectomy procedure. This means you need good quality venography and intravascular ultrasound to unearth such a lesion. At present there’s a little debate as to whether stenting should take place during the index thrombectomy procedure, but my position is that if you’ve identified the cause of the thrombotic event, it should be treated at that time to prevent re-thrombosis.”

Professor Desai closed the interview by summarizing his take-home message regarding when and how to treat with thrombectomy. “We have guidance from high-quality research that shows us which patients to select, how to select those patients, and what we can do to achieve reasonable outcomes,” he said. “Now maybe we can even improve on that further, because the technologies used in those studies are older and have since evolved. So we need to look to newer studies to show how to best optimize our newer tools.”

REFERENCES

1. Vedantham S, Goldhaber SZ, Julian JA, et al. Pharmacomechanical catheter-directed thrombolysis for deep-vein thrombosis. N Engl J Med. 2017;377(23):2240-2252. 

2. Comerota AJ, Kearon C, Gu CS, et al. Endovascular thrombus removal for acute iliofemoral deep vein thrombosis. Circulation. 2019;139(9):1162-1173.

3. BOLT: Study of the Indigo® Aspiration System when used in patients with deep vein thrombosis. ClinicalTrials.gov Identifier: NCT05003843. Available at: https://clinicaltrials.gov/ct2/show/NCT05003843 

4. DEFIANCE: RCT of ClotTriever System Versus Anticoagulation In Deep Vein Thrombosis. ClinicalTrials.gov Identifier: NCT05701917. Available at: https://clinicaltrials.gov/ct2/show/NCT05701917 

5. Dexter DJ, Kado H, Schor J, et al. Interim outcomes of mechanical thrombectomy for deep vein thrombosis from the All-Comer CLOUT Registry. J Vasc Surg Venous Lymphat Disord. 2022;10(4):832-840.e2.