Stent Thrombosis after Endovascular Treatment of Iliofemoral or Caval Veins in Patients with Postthrombotic Syndrome

Following acute deep vein thrombosis, 20 to 50% of patients will develop the postthrombotic syndrome (PTS), despite optimal antithrombotic therapy.[1] Venous remodeling underlies the pathophysiology of PTS and clinically manifests as painful leg edema, hyperpigmentation, venous ectasia, and, sometimes, ulcers ([Fig. 1]).[2] PTS is associated with a significant financial and morbidity burden, and reduced patient-reported health quality of life measures.[1] [2] There have been considerable efforts in improving the prediction[3] [4] [5] and prevention[6] [7] [8] of PTS in recent years. Indeed, the prevention of PTS has focused on use of external compression stockings, different forms of antithrombotic therapy, anti-inflammatory drugs, and acute endovascular interventions such as catheter-directed thrombolysis, all of which have provided conflicting results about efficacy. Similarly, the treatment of established PTS is unclear given the lack of well-designed studies and evidence-based management strategies.

Fig. 1 Pathophysiology of postthrombotic syndrome.

A subset of patients with severe PTS may derive benefit from endovascular therapy, namely those with chronic iliac vein obstruction. Image-guided, catheter-based stent placement in patients with residual iliofemoral venous obstruction has been associated with high technical success rates and patient-reported symptom relief.[9] [10] However, the overall quality of evidence for important clinical outcomes, including complications, appears to be low. Stent thrombosis (ST) is a particularly feared complication of endovascular venous stenting that may limit its uptake in patients with PTS. However, details relating to the timing of ST following stent insertion, risk factors for ST development and impact of different antithrombotic regimens on ST have not been well characterized.

Against this background, Sebastian et al conducted a subgroup analysis of 136 patients with PTS and venous stent implants enrolled in the Swiss Venous Stent Registry to shed light on the timing, the incidence, and risk factors for ST during and after antithrombotic therapy.[11]

Early discontinuation of antithrombotic therapy occurred more commonly in patients who were young, female, and had May-Thurner syndrome, whereas patients with more severe PTS at baseline continued anticoagulation. These patients were more often obese and had a history of recurrent venous thrombotic events. Antithrombotic therapy was given to 96% of patients for at least 3 months; 32% completed a median duration of 12 months of treatment. Approximately half of patients (46%) were started on low-molecular-weight heparin after stent insertion before transitioning to an oral agent, most often a direct oral anticoagulant.

Continued antithrombotic therapy did not appear to impact on the development of ST or recurrent venous thrombotic events. Similarly, the type of oral anticoagulant (i.e., vitamin K antagonist vs. direct oral anticoagulant) did not influence ST rates. ST occurred in 20% of patients, at a median of 96 days poststent placement (median = 89 days, interquartile range [IQR] 13–136 in patients who continued antithrombotic therapy, median = 289 days, IQR 69–900 in patients who stopped treatment). The cumulative incidence of ST was greatest within the first 6 months following stent insertion (13.7%, 95% confidence interval [CI]: 7.8–19.6).

Risk factors for development of ST were: age < 40 years (hazard ratio [HR] = 2.26, 95% CI: 1.03–4.94), stent insertion distal to the common femoral vein (HR = 3.03; 95% CI: 1.28–7.19), and the presence of postthrombotic femoral inflow veins (HR = 2.92; 95% CI: 1.36–6.25). Interestingly, a diagnosis of May-Thurner syndrome was associated with a reduced risk for ST (HR = 0.37; 95% CI: 0.15–0.91).

Endovascular stent placement was highly efficacious in maintaining venous recanalization, with a 99% primary treatment success rate. Moreover, stent placement was associated with improvements in the Villalta score (median 5-point reduction, IQR 1–7) and revised venous clinical severity score (median 3-point reduction, IQR 0–6), with 66% of patients free from PTS symptoms at the time of last follow-up. Bleeding events complicated 15% of patients, with no major difference among patients who continued antithrombotic therapy (14%) and those who did not (16%).

The main findings from this study help to address the paucity of data regarding clinical outcomes and complications of endovascular stent placement for PTS. The majority of venous stent thrombosis occurred during anticoagulant therapy, although the quality of anticoagulation, namely time in therapeutic range while receiving warfarin, was not reported. Moreover, patients receiving continued anticoagulant therapy were at higher baseline risk of thrombosis compared with those who stopped anticoagulation early, making it difficult to assess the comparative efficacy of anticoagulation in preventing ST in PTS. Nonetheless, these findings highlight the role of alternative risk factors such as younger patient age, distal stent insertion, and postthrombotic venous collateralization in ST development. Whether patients with these risk factors warrant more aggressive monitoring for ST or combination anticoagulant–antiplatelet therapy remains uncertain.

Antithrombotic management strategies following endovascular venous stent insertion are inconsistent and lack uniform consensus among major societal guidelines.[12] [13] [14] Moreover, the ideal anticoagulant regimen is uncertain. Although the results from the study of Sebastian et al suggest no difference with treatment using low-molecular-weight heparin, vitamin K antagonists, or direct oral anticoagulants, the study sample size was small and application of the study findings are limited to patients receiving self-expanding nitinol venous stents. Whether these findings can be applied to patients receiving alternative types of endovascular venous stents (i.e., stainless steel, covered stent grafts, etc.) also is uncertain. Adjunct antiplatelet therapy was used in 15% of patients in this study but details relating to the type, dose, duration, anticoagulant pairing, and specific outcome measures relative to patients receiving anticoagulant therapy alone were not reported.

While this study represents a step forward toward defining outcomes in patients with PTS and venous stents, several important questions remain. Results of the randomized, controlled, open-label ARIVA trial (EudraCT registration number: 2019–001723–12) comparing aspirin and rivaroxaban to rivaroxaban alone in patients with endovascular venous stents will be key in determining the optimal antithrombotic strategy in patients with venous stents. Moreover, the ongoing C-TRACT trial (#NCT03250247), a randomized-controlled trial evaluating the role of endovascular therapy in patients with iliac obstructive PTS will help to shed further light on the comparative efficacy and safety of endovascular venous stenting for treatment of PTS. The management of PTS remains one of the most challenging situations in patients with thrombotic vascular disease. Efforts by Sebastian et al aimed at improving patient outcomes are welcome but more work is needed.

• References

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