Twelve-month clinical outcomes of a hybrid oblique self-expanding nitinol stent used for the treatment of post-thrombotic syndrome with common iliac vein compression: The TOPOS study

The majority of patients with iliofemoral deep vein thrombosis (DVT) have an underlying iliac vein compression. ¹ Approximately 50% develop the post-thrombotic syndrome (PTS) if treated conservatively. ² As in May–Thurner syndrome, common iliac vein lesions are typically located close to the iliocaval confluence and are caused by iliac vein compression from overriding iliac arteries against the spine. Conventional non-oblique stents had been used for many years to treat iliac vein compression syndromes by extending the stent across the iliocaval confluence into the inferior vena cava, thereby jailing the contralateral outflow. The risk of contralateral DVT with a conventional stent was 10% after 5 years. ³ A self-expandable nitinol stent with a 35° oblique-shaped proximal end (sinus-Obliquus; Optimed, Ettlingen, Germany) was designed for the treatment of common iliac vein compression to minimize contralateral outflow obstruction (figure in the online supplemental material).

In the prospective, international, monitored, single-arm TOPOS (Treatment Of Post-thrombotic syndrome with the Oblique Stent) study, we included 60 consecutive PTS patients who required endovascular therapy and who were treated with the self-expandable oblique stent for unilateral common iliac vein obstruction. TOPOS recruited from experienced centers that performed at least 30 deep venous interventions per year. We have described the study specifics and methodology previously. ⁴ All participants provided written informed consent and the study was approved by local research ethics committees. In brief, stent extension of the oblique stent in or below the external iliac vein was permitted using the sinus-XL Flex or sinus-Venous stents (both from Optimed) in the case of insufficient stent inflow. TOPOS did not mandate the use of intravascular ultrasound (IVUS). Follow-up visits were scheduled for 3, 6, 12, and 24 months following the procedure, each of which included a duplex ultrasound exam for stent patency evaluation. The course of clinical signs and symptoms was estimated with the Villalta score and revised venous clinical severity score (rVCSS), as well as the patient based visual analog scale for pain (VAS) and the chronic lower limb venous insufficiency questionnaire (CIVIQ-20).^5–7 Recently, all remaining study participants had completed the 12-month follow-up visit.

The primary outcome was the primary patency rate at 12 months. The secondary outcomes were primary assisted patency, secondary patency, and changes in signs and symptoms at 12 months relative to baseline using the aforementioned clinical scores. Stent patency rates have been outlined in accordance with the reporting standards of the Society for Vascular Surgery. ⁸ In case of an inconclusive ultrasound exam, it was adjudicated for the worst-case scenario (non-patency). We calculated 12-month incidences for the primary and secondary outcomes accompanied by the corresponding 95% CI. The mean values of continuous dependent variables, namely the clinical scores for PTS, were compared at baseline and follow-up by analysis of covariance (ANCOVA). SAS software, Version 9.4 (SAS Institute Inc., Cary, NC, USA) served for statistical analysis.

Two patients withdrew informed consent, and five patients were lost to follow-up. At baseline, 43% of patients had a mild (Villalta score: 5–9 points), 30% had a moderate (10–14 points), and 27% had a severe PTS (> 14 points) according to the Villalta classification. At baseline, 92% of patients reported difficulties while exercising, 87% had pain in their ankles or thighs, and 13% had active venous ulcers. Seventy percent of patients had extensive post-thrombotic disease requiring stent extension below the inguinal ligament. Patient characteristics and procedural details are displayed in Table 1. Type and duration of antithrombotic therapy was left to the treating physician. At 6 months, 56 patients had ongoing oral anticoagulation therapy (OAC): 47 had direct oral anticoagulants (DOACS), nine vitamin-K antagonists (VKA), and 12 additional platelet inhibitors. At 12 months, 45 patients had ongoing OAC: 37 had DOACs, eight VKA, and six additional platelet inhibitors.

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Table 1.

Study data

Parameter	Value
Patient characteristics
Age, years	46.6 ± 14.9
Female sex	41 (68%)
BMI, kg/m2	26.3 ± 5.0
Multiple events of DVT	14 (23%)
Previous PE	13 (22%)
Procedural details
Side of intervention: left	54 (90%)
Mean number of stents	1.9 ± 0.6
Mean stent lengths, cm	22.0 ± 7.6
Stent extension	48 (80%)
Below inguinal ligament	42 (70%)
Outcomes	Baseline	3-month visit	6-month visit	12-month visit
Primary outcome
Primary patency, % [95% CI]	–/–	93.1% a [83.3–98.1%]n = 58	87.5% a [75.9–94.8%]n = 56	83.0% a [70.2–91.9%]n = 53
Secondary outcomes
Primary assisted patency, % [95% CI]	–/–	93.1%[83.3–98.1%]n = 58	91.1% a [80.4–97.0%]n = 56	90.6% a [79.3–96.9%]n = 53
Secondary patency, % [95% CI]	–/–	100%[93.8–100%]n = 58	98.2% a [90.3–100%]n = 56	98.1% a [89.7–100%]n = 53
Villalta score, median (IQR)	10 (6–16)n = 60	3 (1–6)n = 53	3 (2–4)n = 53	3 (1–5)n = 52
rVCSS, median (IQR)	8 (6–11)n = 59	4 (2–7)n = 55	4 (3–6)n = 52	3 (1–5)n = 51
VAS for pain, median (IQR)	4 (3–6)n = 59	1 (0–2)n = 53	1 (0–2)n = 52	1 (0–2)n = 51
CIVIQ-20, median (IQR)	45 (36–56)n = 59	27 (22–36)n = 53	26 (23–38)n = 55	27 (23–35)n = 51

a

Percentages are based on non-missing values. Two patients had inconclusive duplex ultrasound exams and were adjudicated for the worst-case scenario.

BMI, body mass index; CIVIQ-20, chronic venous disease quality of life questionnaire; DVT, deep vein thrombosis; PE, pulmonary embolism; rVCSS, revised venous clinical severity score; VAS, visual analog scale.

At 12 months, primary, assisted primary, and secondary patency rates were 90% (95% CI 55.5–99.7%), 100% (95% CI 69.2–100%), and 100% (95% CI 69.2–100%) in patients with the self-expandable oblique stent only, and 81.4% (95% CI 66.6–91.6%), 88.4% (95% CI 74.9–96.1%), and 97.6% (95% CI 87.4–99.9%) in patients with stent extension below the inguinal ligament, respectively. Overall, eight (13%) patients (seven with stent extension) underwent re-intervention to maintain treatment success (three were treated for stent stenosis, five for stent occlusion); six had therapeutic-dose anticoagulation therapy at time of diagnosis. The primary and secondary outcomes are displayed in Table 1. At 12 months, 60% of patients were free from PTS; 18% had mild, 7% moderate, and 2% severe PTS. Mean improvement in Villalta, rVCSS, CIVIQ-20, and VAS from baseline to follow-up was 8.4 ± 6.9 (95% CI 6.5–10.3; p < 0.0001; n = 52) points, 5.1 ± 3.5 (95% CI 4.1–6.1; p < 0.0001; n = 51) points, 15.6 ± 12.4 (95% CI 12.1–19.1; p < 0.0001; n = 50) points, and 2.9 ± 2.2 (95% CI 2.3–3.5; p < 0.0001; n = 50) points, respectively. At 12 months, 37% of patients reported difficulties while exercising, 38% pain in their ankles or thighs, and none had active venous ulcers. No patient developed contralateral DVT, pulmonary embolism, or major bleeding during 12 months of follow-up. Routine assessment of stent fracture was not ascertained.

In conclusion, endovascular therapy of PTS with the self-expandable oblique venous stent and provisional extension resulted in a high primary patency rate and improvement of PTS and quality of life through 1 year. Lower patency rates were observed in patients with stent extension, which is most likely related to post-thrombotic femoral vein inflow. ⁹ The 2-year follow-up of TOPOS will permit an indirect comparison of patency rates with historical data of conventional non-oblique stents.