Examining the viability of interventional treatment for iliofemoral DVT

ATTRACT compared outcomes following pharmacomechanical thrombolysis (PMT) versus standard medical therapy (SMT), and while no benefit with PMT was demonstrated for femoropopliteal deep vein thrombosis (DVT), subgroup analysis of iliofemoral DVT demonstrated a reduction in moderate-to-severe post thrombotic syndrome (PTS).^1,2 However, was the benefit demonstrated enough to counteract the increased cost of PMT? In this article for Venous News, Anna Pouncey (Guy’s and St Thomas’ Hospital, London, UK) explains.

A recent cost-effectiveness analysis on the ATTRACT trial, published in Circulation, presents a discouraging picture.³ The model yielded an estimated ICER (Incremental Cost Effectiveness Ratio) of US$137,526 per QALY (Quality Adjust Life Year) for PMT of iliofemoral DVT.3 In contrast, prior work from CaVenT presented an economically favourable ICER of US$20,439 per QALY gained with use of CDT versus anticoagulation. So, what could have led to such a drastically divergent conclusion?

Firstly, clinical benefit observed in the ATTRACT trial was much smaller than that observed in the CaVenT trial (+0.12 [+US$16,473] vs. +0.63 [+US$12,843] QALYS), which had a negative effect on model outcome.^3,4 Authors state that from this model, the relative risk (RR) of development of PTS would need to be <0.65 to be cost effective. This may be achievable with careful patient selection and modern practice today. Indeed, a Cochrane review of 17 studies with 1,103 participants found the RR of PTS associated with thrombolysis to be 0.64 (95% CI 0.52–0.79, P<0.0001).⁵

Controversially, authors chose to incorporate femoropopliteal patients into the cost-effectiveness model. Interventional treatment for femoropopliteal DVT was not clinically effective, and therefore could not be cost-effective. Disappointingly, secondary analysis of the clinically relevant iliofemoral DVT cohort, for whom outcomes and costs are quite different, is not clearly described. Thus, we arrive at the same quandary as the primary outcome of the ATTRACT trial, with the strength of analysis muddied by inclusion of femoropopliteal DVT.

A major driver in determining cost-benefit from interventional treatment of iliofemoral DVT is from the reduction in PTS. In this model, insufficient emphasis was placed on long-term increased healthcare costs associated with increased PTS severity. Costing was not in line with prior work done by MacDougall, who estimated a US$4,726 average annual cost difference for a patient with PTS (US$6132 in 2017 dollars).^6,7 The cost of ulcers (which occur in 5–10% of PTS cases, costing roughly $10,000 per year) is also underestimated.^8,9 Several assumptions were also made regarding the impact of PMT on PTS outcomes that are not empirically verifiable, such as the assumption that transition to less severe PTS categories (improvement in symptoms) beyond the first six months could not occur.³

Costs at the index event are also much less in the SMT arm than typical Medicare events seen in 2017 for diagnostic-related groupings 294 and 295 (US$3,877 vs. US$7,843). The ATTRACT report does not go into detail about the costing of the control arm, but this difference in cost may reflect treatment of patients with less severe presentations in the outpatient setting. Additionally, ATTRACT findings may have incorporated some bias, as late intervention was discouraged, substantial loss to follow up occurred, and patient selection criteria led to a study population sample with limited generalisability.¹⁰

So, could interventional treatment for iliofemoral DVT be shown to be viable? Yes, potentially, if modern practice delivers good outcomes and if costing for PTS is fully accounted for. But, once again this study has concluded that the strength of ATTRACT data for iliofemoral DVT is lacking.³ If we want an answer, there is a need for the venous community to move on from ATTRACT and return to a state of equipoise, enabling well-designed prospective studies that generate representative data.

References:

1. Comerota AJ, Kearon C, Gu C-S, Julian JA, Goldhaber SZ, Kahn SR, et al. Endovascular Thrombus Removal for Acute Iliofemoral Deep Vein Thrombosis. Circulation 2019;139:1162–73.
2. Vedantham S, Goldhaber SZ, Julian JA, Kahn SR, Jaff MR, Cohen DJ, et al. Pharmacomechanical Catheter-Directed Thrombolysis for Deep-Vein Thrombosis. N Engl J Med 2017;377:2240–52.
3. Magnuson EA, Chinnakondepalli K, Vilain K, Kearon C, Julian JA, Kahn SR, et al. Cost-Effectiveness of Pharmacomechanical Catheter-Directed Thrombolysis Versus Standard Anticoagulation in Patients with Proximal Deep Vein Thrombosis: Results from the ATTRACT Trial. Circ Cardiovasc Qual Outcomes 2019;12:e005659.
4. Enden T, Wik HS, Kvam AK, Haig Y, Kløw NE, Sandset PM. Health-related quality of life after catheter-directed thrombolysis for deep vein thrombosis: secondary outcomes of the randomised, non-blinded, parallel-group CaVenT study 2013:1–7.
5. Watson L, Broderick C, Armon MP. Thrombolysis for acute deep vein thrombosis. Cochrane Database Syst Rev 2014:CD002783.
6. Kachroo S, Boyd D, Bookhart BK, LaMori J, Schein JR, Rosenberg DJ, et al. Quality of life and economic costs associated with postthrombotic syndrome. Am J Heal Pharm 2012;69:567–72.
7. MacDougall DA, Feliu AL, Boccuzzi SJ, Lin J. Economic burden of deep-vein thrombosis, pulmonary embolism, and post-thrombotic syndrome. Am J Heal Pharm 2006;63:S5–15.
8. Heit JA, Rooke TW, Silverstein MD, Mohr DN, Lohse M, Petterson TM, et al. Trends in the incidence of venous stasis syndrome and venous ulcer: A 25-year population-based study 2001;55905:1022–7.
9. Barnsbee L, Cheng Q, Pacella R, Tulleners R, Lee X. Measuring costs and quality of life for venous leg ulcers 2019:112–21.
10. Vedantham S, Goldhaber SZ, Julian JA, Kahn SR, Jaff MR, Cohen DJ, et al. Pharmacomechanical Catheter-Directed Thrombolysis for Deep-Vein Thrombosis. N Engl J Med 2017;377:2240–52.

Anna Pouncey is a vascular surgeon currently training in the London Deanery, London, UK.

The author has no disclosures.