A Creative Application to Leverage Thrombectomy Tools to Achieve Flow Restoration

VASCULAR DISEASE MANAGEMENT 2023;20(1):E1-E3

It is a pleasure to provide a guest editorial in this month’s issue of Vascular Disease Management. Mohannad Bisharat, MD has related a unique case of ClotTriever (Inari Medical) thrombectomy within a femoralfemoral venous bypass in his article “Patency Restored to an Occluded Femoralfemoral Venous Bypass Graft With the ClotTriever Thrombectomy System.” This creative application highlights the ability to leverage thrombectomy tools to achieve flow restoration, even outside of traditional venous thromboembolic (VTE) disease.

Certainly, technological advances have outpaced the data in support of these devices for thrombectomy applications. Earlier randomized trials have suggested equipoise with an endovascular first approach over surgery with regards to acute limb ischemia.¹ Within the deep vein thrombosis (DVT) space, there exists a paucity of data. Early experience suggested benefit for the use of catheter-directed thrombolysis (CDT) for treatment of DVT. It was reported that there was less post-thrombotic syndrome (PTS) with CDT in the CaVenT randomized control trial (RCT) and less rethrombosis and improved quality of life in the PEARL registry.^2,3 However, the ATTRACT RCT found no difference in PTS and higher bleeding rates with the use of pharmacomechanical catheter-directed thrombolysis.⁴ As a result of ATTRACT, the enthusiasm for routine DVT thrombectomy has rightly been dampened. There are several criticisms of this trial, including a long enrollment period; use of older, perhaps less effective mechanical thrombectomy technologies; and lack of intravascular ultrasound to identify outflow pathologies and residual clot burden. Yet there was improvement in acute symptoms, especially in the iliofemoral subgroup and younger patients.⁵

Clot removal devices for VTE fall into several general broad categories: catheter-directed thrombolysis, pharmacomechanical thrombectomy (combination thrombolytic with mechanical thrombectomy), clot aspiration (manual and powered), clot fragmentation (sometimes with aspiration), and clot extraction. Several devices also utilize hybrid modalities.

This list is by no means comprehensive and does not include multiple other novel devices or variations currently in development or in preclinical status. Newer technologies will focus on more efficient methods of separating blood from thrombus, reducing blood loss and enhancing clot removal. This need goes beyond simple safety as it will reduce overall procedural times and may improve clinical outcomes while addressing residual clot burden. Concerns have also been raised regarding rethrombosis issues in patients undergoing mechanical thrombectomy. Some have postulated that simply focusing on outflow (iliofemoral thrombus) does not address important inflow sites, such as the profundal/deep femoral vein or the popliteal vein, which may impact patency post intervention if adequate flow is not present. Intimal injury may be another potential problem that could be seen with multiple devices that apply more wall pressure (eg, extraction devices). Perhaps this could be mitigated with better pharmacologic therapies post or intra-intervention. Enoxaparin for 4 weeks prior to direct oral anticoagulants may have some anti-inflammatory effects. Subintimal steroid injections are being studied as an adjunctive therapy to mechanical thrombectomy.⁶ Moreover, addressing chronic thrombus creates even more technical and clinical challenges with issues of vein retraction, clot morphologic change into tissue indistinguishable from collagen, and incomplete clot dissolution with only partial recanalization from the innate fibrinolytic mechanisms. Currently available devices often prove inadequate in addressing these types of challenging thrombotic patients.

As we continue to advance technologies, data will slowly be generated. The DEFIANCE RCT will look at ClotTriever thrombectomy compared with anticoagulation alone.⁷ However, a hierarchical composite of treatment failure and PTS severity at 6 months may be less meaningful given the short duration.⁷ Prior data have shown that often PTS presents even out to 24 months post DVT. BOLT is a single-arm study with the Indigo aspiration system (Penumbra) that will examine several outcomes out to 24 months but will be limited due to lack of randomization and potential for bias.⁸

Despite these limitations, technological advancement in the thrombectomy space should continue. It is estimated that the global thrombectomy market will represent $2.27 billion by 2030, which makes it an obvious target for ongoing investment.⁹ But design of better studies and understanding of meaningful clinical outcomes will help inform the appropriate development of these tools. Ultimately, this will be for the benefit of patients, physicians, and our industry partners.

REFERENCES

1. Enezate TH, Omran J, Mahmud E, et al. Endovascular versus surgical treatment for acute limb ischemia: a systematic review and meta-analysis of clinical trials. Cardiovasc Diagn Ther. 2017;7(3):264-271. doi:10.21037/cdt.2017.03.03

2. Haig Y, Enden T, Grøtta O, et al. Post-thrombotic syndrome after catheter-directed thrombolysis for deep vein thrombosis (CaVenT): 5-year follow-up results of an open-label, randomised controlled trial. Lancet Haematol. 2016;3(2):e64-71. doi:10.1016/S2352-3026(15)00248-3

3. Garcia MJ, Lookstein R, Malhotra R, et al. Endovascular management of deep vein thrombosis with rheolytic thrombectomy: final report of the prospective multicenter PEARL (peripheral use of AngioJet rheolytic thrombectomy with a variety of catheter lengths) registry. J Vasc Interv Radiol. 2015;26(6):777-785. doi:10.1016/j.jvir.2015.01.036

4. 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. doi:10.1056/NEJMoa1615066

5. Comerota AJ, Kearon C, Gu CS, et al. Endovascular thrombus removal for acute iliofemoral deep vein thrombosis. Circulation. 2019;139(9):1162-1173. doi:10.1161/CIRCULATIONAHA.118.037425

6. Perivenous dexamethasone therapy: examining reduction of inflammation after thrombus removal to yield benefit in acute femoropopliteal DVT (DEXTERITY-AFP). ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT04862468. Accessed January 16, 2023.

7. Inari Medical Announces Results from the Fully Enrolled 800-patient US Cohort of the FlowTriever FLASH Registry. Inari Medical, Inc. https://ir.inarimedical.com/news-releases/news-release-details/inari-medical-announces-results-fully-enrolled-800-patient-us. Published September 19, 2022. Accessed September 23, 2022.

8. Bolt: Study of the Indigo® aspiration system when used in patients with deep vein thrombosis. ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT05003843. Accessed January 16, 2023.

9. Global Mechanical Thrombectomy Devices Market. InsightAce Analytic. https://www.insightaceanalytic.com/report/global-mechanical-thrombectomy-devices-market/1212. Published March 9, 2022. Accessed January 16, 2023.