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06-29-2020 09:59

The future of deep venous care: Iliac-obstructive post-thrombotic syndrome and the C-TRACT Trial nRSQvaUhRsidBzdkyI3v_Twitter_Bird2.png

By Kush R. Desai, MD, FSIR  Summer 2020

At a glance
  • Studies show that some changes of chronic deep venous obstructive disease resulting from iliac-obstructive PTS, such as illiac vein obstruction and saphenous reflux, can be favorably treated with endovascular therapy.11-14
  • However, meta-analysis of studies shows patency of iliac vein stents have a primary patency of years, not decades. PTS impacts a wide cross-section of society, including younger patients. Frequent procedures to maintain stent patency may place undue burdens on patients.15
  • These concerns have resulted in low confidence in the impact of intervention on treating iliac-obstructive PTS and could lead to lack of support for reimbursement of endovascular therapy for PTS.
  • This highlights a need for randomized trial data in support of its efficacy—such as the Chronic Venous Thrombosis: Relief with Adjunctive Catheter-directed Therapy (C-TRACT) Trial. 
  • The trial has been carefully designed to accurately measure effects on PTS severity utilizing the VCSS, assess safety and cost metrics, and minimize bias.
  • To succeed, the trial needs support, collaboration and referrals.

Post-thrombotic syndrome (PTS) is a chronic condition that develops in nearly half of all patients following proximal lower extremity deep vein thrombosis (DVT).1,2 Many patients have mild to moderate symptoms, manifested by a variable combination of edema, pain/heaviness, fatigue and paresthesia that can be managed effectively with conservative measures, including compression, rest and elevation. However, approximately half of all PTS patients go on to develop moderate to severe symptoms reflective of iliac vein stenosis or occlusion.3 In these patients, PTS is characterized by a spectrum of debilitating symptoms including venous claudication that limits normal walking activities due to a “bursting” pain, severe edema that is restrictive to movement and is less responsive to compression therapy, and venous stasis ulceration, which can cause infections and may necessitate operative debridement.4,5 These symptoms can profoundly affect quality of life (QOL); patients with severe PTS have reported the impact to their QOL to be comparable to patients with angina, cancer and congestive heart failure.6,7

Conservative management of iliac-obstructive PTS is centered around anticoagulation, compression therapy and, when necessary, wound care. However, the efficacy of each of these therapies is limited overall. While anticoagulation may prevent progression and recurrence of DVT, PTS often develops nonetheless.1,2 Further, the results of a large, multicenter randomized trial demonstrate that elastic compression does not lower PTS incidence,8 with other studies demonstrating limited evidence of efficacy in symptom reduction in patients suffering from severe PTS.9 Finally, once a venous ulcer develops, patients find themselves with symptoms that wax and wane, requiring frequent wound care when an active ulcer is present. Thus, patients with iliac-obstructive PTS find themselves with a paucity of effective, durable therapies.

       By Kush R. Desai, MD, FSIR

Ambulatory venous hypertension is the final common pathway in iliac-obstructive PTS, resulting from a combination of venous obstruction and reflux.4,10 While some of the changes of chronic deep venous obstructive disease are irreversible, iliac vein obstruction and saphenous reflux can be corrected with endovascular therapy and are frequently treated by interventional radiologists. Iliac vein stents have long been placed for treatment of chronic iliac vein stenosis or occlusion, with several studies demonstrating efficacy in reduction of symptoms of iliac-obstructive PTS. The largest study examined 464 patients with post-thrombotic obstruction and noted significant reductions in swelling and pain, as well as ulcer healing in nearly 70% of patients.11 Iliac vein stent placement has also been shown to improve symptoms of venous claudication and calf pump dysfunction.12 Similarly, endovenous ablation for saphenous reflux has long been performed by interventional radiologists, and two studies have demonstrated the potential value of treating saphenous reflux following iliac stent placement in patients with iliac-obstructive PTS, with a nearly 70% ulcer healing rate.13,14

However, there is equipoise regarding the durability of endovascular therapy in the treatment of iliac-obstructive PTS, particularly iliac vein stent placement. A meta-analysis of 37 studies found a combined 79% 1-year primary patency of iliac vein stents placed in post-thrombotic obstructions, with a projected primary patency of 60% at 5 years.15 This issue is particularly vexing, as PTS affects a wide cross section of society. Unlike other vascular diseases that typically afflict an older population, younger patients are frequently affected by PTS, and concerns over stent patency become a matter of decades, not years. In such patients, if frequent procedures are required to maintain patency, this may place an undue burden on patients with high associated cost. Further, most endovascular therapy studies are retrospective, unblinded and of a modest sample size with limited follow-up, underscoring the significant risk for a bias and potential overstatement of procedural efficacy.

These concerns are reflected in an overall lack of confidence that regulators have in endovascular PTS therapy. In a 2016 Medicare Evidence Development and Coverage Advisory Committee Meeting, the convened panel noted a “very low” level of confidence that any intervention improved health care outcomes in patients with iliac-obstructive PTS; they further highlighted the lack of randomized trial data in support of endovascular therapy, as well as the significant potential risk for morbidity related to intervention. If this sentiment persists due to the lack of high-quality data, it is possible that payers will follow suit and will no longer support reimbursement of endovascular therapy for PTS.

If this sentiment persists due to the lack of high-quality data, it is possible that payers will follow suit and will no longer support reimbursement of endovascular therapy for PTS.

Given that iliac-obstructive PTS can lead to severe disability, patients with this condition deserve high-quality data that accurately reflects the efficacy, safety and costs associated with a potentially corrective intervention. The current lack of consensus can best be addressed by a multicenter, randomized, controlled trial with systematic efforts to minimize bias. The Chronic Venous Thrombosis: Relief with Adjunctive Catheter-directed Therapy (C-TRACT) Trial, led by Suresh Vedantham, MD, FSIR, is an example of interventional radiology taking leadership in research efforts of the highest quality and integrity, aimed at answering critical clinical questions with broad implications. In this trial, patients with prior history of DVT and current moderate to severe PTS (utilizing a venous clinical severity score [VCSS] of 8 or greater, or Villalta score of 10 or greater) are enrolled and randomized to receive either the best supportive therapy, or endovascular therapy with stent placement and possible saphenous ablation. The trial has been carefully designed to accurately measure effects on PTS severity utilizing the VCSS, assess safety and cost metrics, and minimize bias via central randomization, blinded assessments and equal surveillance of both arms. SIR Foundation was among the first professional societies to support this critical research effort, leading the way for broad multisociety support.

The value of this trial to patients with iliac-obstructive PTS is enormous; the results have the potential to make a significant impact on the lives of patients with this debilitating condition. However, trials like this are a massive undertaking and require the broad support of the IR community; this includes referral of potential patients to trial sites or joining the trial as an investigator if PTS intervention represents a significant portion of your clinical practice. As members of SIR, support of this trial drives high-quality research and firmly demonstrates our commitment to delivering care backed by the highest quality of evidence.

Hear more about the C-TRACT Trial from Dr. Vedantham in episode 5 of The Kinked Wire podcast at bit.ly/3b3At1L. Learn more about this IRQ podcast at sirweb.org/kinkedwire. Learn more about the trial at bloodclotstudy.wustl.edu/c-tract.

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. Kahn SR, Shrier I, Julian JA, et al. Determinants and time course of the postthrombotic syndrome after acute deep venous thrombosis. Ann Intern Med. 2008;149(10):698–707.
  3. Comerota AJ, Kearon C, Gu CS, et al. Endovascular thrombus removal for acute iliofemoral deep vein thrombosis. Circulation. 2019;139(9):1162–1173.
  4. Strandness DE, Jr., Langlois Y, Cramer M, Randlett A, Thiele BL. Long-term sequelae of acute venous thrombosis. JAMA. 1983;250(10):1289–1292.
  5. Delis KT, Bountouroglou D, Mansfield AO. Venous claudication in iliofemoral thrombosis: long-term effects on venous hemodynamics, clinical status, and quality of life. Ann Surg. 2004;239(1):118–126.
  6. Kahn SR, Hirsch A, Shrier I. Effect of postthrombotic syndrome on health-related quality of life after deep venous thrombosis. Arch Intern Med. 2002;162(10):1144–1148.
  7. Kahn SR, Shbaklo H, Lamping DL, et al. Determinants of health-related quality of life during the 2 years following deep vein thrombosis. J Thromb Haemost. 2008;6(7):1105–1112.
  8. Kahn SR, Shapiro S, Wells PS, et al. Compression stockings to prevent post-thrombotic syndrome: A randomised placebo-controlled trial. Lancet. 2014;383(9920):880–888.
  9. Cohen JM, Akl EA, Kahn SR. Pharmacologic and compression therapies for postthrombotic syndrome: A systematic review of randomized controlled trials. Chest. 2012;141(2):308–320.
  10. Shull KC, Nicolaides AN, Fernandes e Fernandes J, et al. Significance of popliteal reflux in relation to ambulatory venous pressure and ulceration. Archives of surgery. 1979;114(11):1304–1306.
  11. Neglen P, Hollis KC, Olivier J, Raju S. Stenting of the venous outflow in chronic venous disease: long-term stent-related outcome, clinical, and hemodynamic result. J Vasc Surg. 2007;46(5):979–990.
  12. Delis KT, Bjarnason H, Wennberg PW, Rooke TW, Gloviczki P. Successful iliac vein and inferior vena cava stenting ameliorates venous claudication and improves venous outflow, calf muscle pump function, and clinical status in post-thrombotic syndrome. Ann Surg. 2007;245(1):130–139.
  13. Nayak L, Hildebolt CF, Vedantham S. Postthrombotic syndrome: feasibility of a strategy of imaging-guided endovascular intervention. J Vasc Interv Radiol. 2012;23(9):1165–1173.
  14. Neglen P, Hollis KC, Raju S. Combined saphenous ablation and iliac stent placement for complex severe chronic venous disease. J Vasc Surg. 2006;44(4):828–833.
  15. Razavi MK, Jaff MR, Miller LE. Safety and effectiveness of stent placement for iliofemoral venous outflow obstruction: Systematic review and meta-analysis. Circ Cardiovasc Interv. 2015;8(10):e002772.

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