Antithrombotic therapies for patients with acute iliofemoral deep vein thrombosis following endovenous recanalization: A single-center study and literature review

Abstract

Objectives

There is no consensus regarding the optimal antithrombotic therapy following endovenous recanalization. We aim to assess the effectiveness of anticoagulant, antiplatelet, or combination therapy to provide evidence-based recommendations for antithrombotic therapy following interventional procedures.

Methods

An Institutional Review Board approved, retrospective study of patients presented to our facility with iliofemoral venous thrombosis requiring thrombolysis and/or thrombectomy with or without venous angioplasty/stenting between January 1, 2010 and April 1, 2023. Incidence of vein or stent patency, thrombosis, and bleeding were considered primary endpoints and were compared between patients on anticoagulant, antiplatelet, or combination therapies at each post-interventional surveillance, up to five visits.

Results

The cohort yielded 128 patients, including 116 adults and 12 minors. We identified a notable trend in the post-recanalization medical routines of patients: those initially prescribed combination therapy post-procedure eventually transitioned to either exclusive anticoagulant or antiplatelet therapy. The initial combination antithrombotic therapy was associated with trends towards higher vein patency (59% vs 47% with anticoagulant vs 25% antiplatelet, p = .3), less recurrent vein and stent thrombosis (46% vs 54% with anticoagulants vs 100% antiplatelet, p = .10), and overall low major bleeding complications (3.2% vs 6.8% anticoagulant, p = .5) at first follow-up compared to those on anticoagulant or antiplatelet regimens alone.

Conclusion

Although the optimal post-interventional antithrombotic therapy remains uncertain, combination therapy was associated with trends towards higher vein patency and lower recurrent thrombosis, with low overall major bleeding complications at the first follow-up visit following interventions. Future studies encompassing larger and more diverse populations are essential to corroborate the findings presented in this report and offer valuable insights for optimizing the management of patients with this condition.

Keywords

Deep vein thrombosis endovenous recanalization antithrombotic therapy

Introduction

Venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE), contributes to significant morbidity and mortality both in the community and in hospitals.¹ It affects as many as 900,000 people in the United States yearly.² Post-thrombotic syndrome (PTS) and PE are two main complications of DVT that can result in major disability and mortality, respectively.³ Anticoagulation with direct oral anticoagulants (DOACs) has shown fewer bleeding complications than vitamin K antagonists (VKA) and has become the standard mainstay treatment for DVT.⁴ However, individuals with severely symptomatic events such as phlegmasia or massive iliofemoral DVT should be considered for endovenous recanalization therapy due to the urgency of these conditions.^4,5 Nonthrombotic etiologies such as vein compression (e.g., nonthrombotic iliac vein lesion) might also benefit from recanalization if symptoms are severe enough to affect daily activities.⁶ Venography with intravenous ultrasound (IVUS) can confirm compression, identify any residual thrombus, and help estimate the degree of stenosis based on pressure gradient and cross-sectional vein diameter reduction. Thrombolysis and/or thrombectomy, followed by venoplasty and or stenting of the iliac veins, are increasingly used to help improve symptoms and reduce the risk of PTS.^7,8 Several studies have demonstrated the safety and effectiveness of catheter-directed thrombolysis (CDT) and subsequent stent placement, reporting high rates of initial technical success and 1-year patency rates.^5,7–9 Although thrombolysis is associated with more rapid and complete lysis, reduced rates of PTS, and higher rates of venous valve function preservation, it does not alter rates of recurrent VTE and mortality when compared with parenteral anticoagulation.^5,7–9 Mechanical thrombectomy (using catheter extraction or fragmentation) or surgical thrombectomy may also be considered an alternative or adjunctive therapy to thrombolysis. It is thought that combined catheter-directed procedures (e.g., thrombolysis plus fragmentation) may further mitigate the risk of bleeding.⁵ Antithrombotic management after interventional treatment for acute DVT remains an uncertain domain, with no large randomized controlled trials or official guidelines establishing an optimal regimen. The existing body of literature is marred by data heterogeneity and incomplete reporting. This is further complicated by rapidly evolving improvements in specialized devices in endovenous intervention.¹⁰

To address the current gaps in antithrombotic therapy following endovenous recanalization, we present a retrospective cohort study including 128 patients at a single center. We further conducted an extensive review of studies on antithrombotic management after endovenous recanalization procedures, aiming to bridge literature gaps and enhance patient care standards.

Material and methods

Single-center chart review

A retrospective chart review of patients who presented at a hospital in Minnesota between January 2010 and April 2023 and were diagnosed with iliofemoral venous thrombosis and had undergone thrombolysis and/or thrombectomy with or without venoplasty/stenting. In general, we treated patients with severe swelling, pain, and/or phlegmasia in the setting of acute occlusive iliofemoral DVT diagnosed within 2-3 weeks from presentation. We included all patients, including those with a history of malignancy, previous VTE, and/or thrombophilia. Patients who did not undergo the procedure of interest, those without follow-up visits, or those who received interventions outside the study period were excluded. The Allina Institutional Review Board approved this study. Informed consent for research review of the medical record was obtained per Minnesota state law.

A standardized data collection form was developed to extract relevant information from the electronic medical records, including demographic details, comorbidities, clinical symptoms, laboratory results, management and interventions, medications, and follow-up notes. Clinical outcomes were followed up to April 1, 2023. Participants were categorized into three groups according to the type of antithrombotic therapy they received: (1) combination (anticoagulation and antiplatelet), (2) anticoagulation, and (3) antiplatelet. To accurately account for patients who changed the type of therapy over the course of the study, we tracked the type of therapy at each follow-up visit.

The dependent variables assessed in this study were vein patency, re-thrombosis, and bleeding events. We defined “vein patency” as whether the treated deep veins were completely free of any thrombosis or stenosis as detected with venous Duplex US and/or computed tomography (CT) venogram following the procedure. IVUS was used when indicated in some cases during initial or repeat intervention. “Re-thrombosis” was defined as the progression of a recanalized segment to either partial or complete occlusion. For bleeding, we used the definition of major bleeding released by the International Society of Thrombosis and Haemostasis (ISTH) as “clinically overt bleeding that was fatal or associated with any of the following criteria: (a) a fall in hemoglobin level of 2 g/dL or more or documented transfusion of at least 2 units of packed red blood cells, (b) involvement of a critical anatomical site (intracranial, spinal, ocular, pericardial, articular, intramuscular with compartment syndrome, retroperitoneal)”.¹² Vein patency, re-thrombosis (including vein and/or stent thrombosis), and bleeding events were assessed and recorded at each follow-up visit for all patients included in the study. The presence of venous obstruction due to thrombosis was recorded and confirmed by expert radiologists and vascular specialists using Duplex US and/or CT venogram. Due to the variability in follow-up visit time after the intervention, we organized follow-up visits by number, from the 1^st up to the 5^th visit following initial presentation and management.

Statistical analysis

Categorical variables were expressed as frequencies (percentages), and continuous variables were expressed as median [interquartile range]. Frequencies were compared using Fisher’s exact test, and medians were compared using the Kruskal-Wallis rank sum test with a critical value of 0.05. Overall median survival time and survival probability by initial therapy were estimated using the Kaplan-Meier method and compared between groups using the log-rank test.

Literature review

A literature review was conducted to contextualize the clinical problem and inform the study design. Peer-reviewed articles, clinical guidelines, systematic reviews, and meta-analyses were identified through database searches in PubMed and MEDLINE using keywords such as “post-intervention anticoagulation therapy,” “iliofemoral venous revascularization,” “antithrombotic therapies,” “deep vein thrombosis,” “catheter-directed thrombolysis,” and “vein stenting.” Studies published within the last 10 years were prioritized to ensure relevance to current clinical practices.

Results

Patient demographics, comorbidities, and presentations

Out of 1293 charts reviewed, 128 patients (116 adults and 12 minors under the age of 18) met the study’s inclusion criteria (Figure 1). Demographics and comorbidities are summarized for each patient in Table 1. The study population comprised both adults (age 18 and above; n = 116) and minor patients (below the age of 18; n = 12) at initial presentations. We opted to incorporate pediatric patients into the study, given that they underwent a consistent management approach for both intervention and medical therapy. 40 percent of patients had a prior history of VTE. Cardiovascular risk factors included in the study are listed in Table 1. Overall, the most common symptom at presentation was leg swelling (89%), followed by leg pain (68%). Most patients presented with vein thrombosis at multiple locations (97%), with the common femoral vein (86%) as the most affected deep vein, followed by the external iliac (80%), common iliac (78%), and femoral vein (77%) (Table 2). Furthermore, over half of the patients (52%) with thrombosis demonstrated May-Thurner syndrome.

Figure 1.

Flow chart of participant inclusion and exclusion.

Table 1.

Demographics and comorbidities of the study population.

Demographics and comorbidities
Characteristic	N = 128^a
Female	81 (63%)
Age	50 (34, 67)
Race
White	114 (89%)
Black or African American	10 (7.8%)
Multiracial	1 (0.8%)
Patient declined	3 (2.3%)
BMI	29 (24, 33)
Unknown	1
VTE
DVT	28 (22%)
PE	4 (3.1%)
DVT & PE	19 (15%)
Neither	77 (60%)
CAD	6 (4.7%)
DM	13 (10%)
Hypertension	32 (25%)
Hyperlipidemia	18 (14%)
MI	3 (2.3%)
COPD	6 (4.7%)
CHF	19 (15%)
CKD	12 (9.4%)
Cerebrovascualr disease	9 (7.0%)
Dyslipidemia	39 (30%)
Tobacco use
Never	72 (56%)
Former	38 (30%)
Current	18 (14%)

^an (%); median (IQR)

Table 2.

Location of vein thrombosis at initial presentation for the study cohort.

Initial vein thrombosis
Characteristic	N = 128^a
Multiple locations	124 (97%)
IVC	47 (37%)
Common iliac vein	100 (78%)
External iliac vein	102 (80%)
Common femoral vein	110 (86%)
Femoral vein	99 (77%)
Popliteal vein	72 (56%)
Calf veins	47 (37%)
Superficial veins	17 (13%)
May-thurner syndrome	67 (52%)

^an (%).

Treatment and outcome

More than half of the patients received interventional treatment for iliofemoral DVT (Table 3): percutaneous mechanical thrombectomy was performed in 88% of the total patients, while 58% of the cohort underwent catheter-directed thrombolysis. Furthermore, 72% of total patients received vein stents. Before the introduction of venous stents, Wallstents were used. However, in cases involving the external iliac or common femoral vein, the Protégé Everflex stent (Medtronic) was utilized. After iliac venous stents became available, Venovo (BD) and Abre (Medtronic) stents were used instead. VICI stents were never used in our patient population. We noted a pattern where many patients, initially prescribed combination therapy post-recanalization procedure, subsequently transitioned to exclusive anticoagulant or antiplatelet therapy alone, as illustrated in Figure 2. Among patients who received antiplatelet regimen in both antiplatelet and combination groups, 30/71 (42%) were on aspirin, 40/71 (56%) were on clopidogrel, and only one patient was on both at discharge. Given the small sample size of our study population, we cannot determine a significant difference between single and dual antiplatelet therapy for this indication. The average time for 1^st follow-up was 38 days, with 50% of the patient cohort on combination therapy, 47% on anticoagulant, and 3% on antiplatelet. The subsequent follow-up exhibited a rising variability in time intervals and a decreasing patient count (Appendix 1).

Table 3.

Catheter-directed interventional treatment received by the study cohort at initial presentation.

Interventional treatment
Characteristic	N = 128^a
Catheter directed thrombolysis	74 (58%)
Catheter directed thrombectomy	113 (88%)
Venoplasty	103 (80%)
Vein stent	92 (72%)
SurgicalIntervention	4 (3.1%)
Exploratory laparotomy^b	1 (0.8%)
Laparotomy via flank incision for abdominal compartment syndrome^b	1 (0.8%)
Primary repair of left external and internal iliac veins^b	1 (0.8%)
Right femoral vein reconstruction with stent graft^b	1 (0.8%)

^an (%).

^bSurgical intervention type.

Figure 2.

Flow chart of the number of patients across different antithrombotic therapies during the five follow-up visits post-intervention.

The immediate effects of the three chosen treatment regimens on vein patency, recurrent thrombosis, and bleeding are shown in Table 4, while outcomes at later visits are reported in Appendix 1. A notable trend (p = .3) was observed toward higher vein patency rates among patients receiving combination therapy (59%), as opposed to those managed with anticoagulation therapy (47%) or antiplatelet therapy alone (25%) (Table 4). The combination group also demonstrated a trend towards a lower incidence of re-thrombosis at vein and/or stent than anticoagulant or antiplatelet (46% vs 54% vs 100% respectively; p = .1). Adjusting for confounders can only be done in a modeling setting (by including the confounding variables in the model along with the group variable and outcome). To address this point by excluding patients with a history of VTE and/or hormonal therapy exposure from Table 4, we notice a slight increase in vein patency and a decrease in vein/stent thrombosis, but it did not seem to change the relationship between outcome and medication (Table 5). Major bleeding rate was minimal across groups and occurred infrequently, with two events in combination therapy, four in anticoagulant, and none in antiplatelet. Notably, the combination groups displayed fewer major bleeding events (3.2%) than the anticoagulant group (6.8%; p = .5).

Table 4.

Outcome at the first post-interventional follow-up visit, categorized by the antithrombotic therapy.

First outcome by therapy
Characteristic	Combination, N = 63^a	Anticoagulant, N = 59^a	Antiplatelet, N = 4^a	p-value^b
Vein patency	37 (59%)	28 (47%)	1 (25%)	0.3
Vein/Stent thrombosis	29 (46%)	32 (54%)	4 (100%)	0.10
Major bleeding	2 (3.2%)	4 (6.8%)	0 (0%)	0.5

^an (%).

^bFisher’s exact test.

Table 5.

Outcome at the first post-interventional follow-up visit categorized by the antithrombotic therapy, excluding patients with a history of VTE and/or hormonal therapy.

First outcome by therapy subgroup^c
Characteristic	Combination, N = 35^a	Anticoagulant, N = 31^a	Antiplatelet, N = 2^a	p-value^b
Vein patency	23 (66%)	17 (55%)	1 (50%)	0.6
Vein/Stent thrombosis	14 (40%)	14 (45%)	2 (100%)	0.3
Major bleeding	0 (0%)	2 (6.5%)	0 (0%)	0.3

^an (%).

^bFisher’s exact test.

^cExcluding patients with history of DVT and/or hormonal therapy.

Discussion

Our study provides insights into the early follow-up outcomes in patients with acute iliofemoral DVT after endovascular interventions, exploring the impact of diverse antithrombotic regimens on vein/stent patency, re-thrombosis, and bleeding events. The first follow-up visit is an important time point to evaluate the initial response to the antithrombotic therapies following endovenous iliofemoral and caval recanalization. Although statistical significance was not reached for differences between therapies, the trends observed with combination therapy suggest higher vein patency, lower re-thrombosis, and overall low major bleeding rates. The low bleeding rate may be attributed to patient selection, where those with lower bleeding risk mainly received combination therapy. Furthermore, clinicians may have avoided recommending combination therapy to patients with high bleeding risk based on comorbidities. Additionally, patients in the combination therapy group may have been transitioned to monotherapy earlier, thereby limiting the likelihood of long exposure and, hence, major bleeding. A comprehensive literature review accompanies our findings, aiming to contextualize them within the broader landscape of antithrombotic therapy outcomes and further evaluate the implications of our results.

Several prior studies have sought to compare different antithrombotic therapies following venous stent placement yet were unable to demonstrate the superiority of any specific antithrombotic agent or regimen. In a systemic review, 86% (12/14) of the included studies involved patients who received anticoagulation therapy, and 33% (4/12) received antiplatelet therapy consisting of aspirin and/or clopidogrel for iliac venous stenting.¹³ Antithrombotic treatment (involving warfarin with INR 2-3 and aspirin in some cases) following venous stent placement was associated with an early re-thrombosis incidence (<30 days from index procedure) of 5% to 25%. Major bleeding was reported in five studies, with incidence rates ranging from 1 to 11%. All patients in these studies received only warfarin. The major bleeding rates (7.8% at first and 5.6% at second follow-ups) of patients on anticoagulants in our study also fall into this range. The review concluded that the choice of agent, dosing, and duration of anticoagulant and antiplatelet remained unclear.

A meta-analysis of 37 studies that included 2869 patients who underwent stent placement for iliofemoral venous outflow obstruction revealed a prevalent usage of VKA treatment for 2–6 months, targeting an INR of 2–3, with an extension to 6–12 months in high-risk patients.¹⁴ The primary patency rates were 96% (95% CI = [93%, 98%]) in nonthrombotic, 87% (95% CI = [80%, 92%]) in acute thrombotic, and 79% (95% CI = [76%, 83%]) in chronic venous obstruction. In another large systemic review performed to assess antithrombotic therapy following venous stenting for acute or chronic thrombotic events involving the iliofemoral veins, only two (4%) directly assessed the effect of antithrombotic therapy on treatment outcomes.¹⁵ One of the two cohort studies included patients with acute iliofemoral DVT treated with catheter-directed thrombolysis (CDT) or pharmacomechanical thrombectomy (PMT) followed by stenting and found that patients treated with rivaroxaban (n = 73) or VKA (n = 38) for a minimum of 3 months following the intervention demonstrated equal stent patency at 24 months.¹⁶ The second cohort study included patients stented for thrombotic (acute or chronic) or nonthrombotic cavo-iliofemoral venous tract obstructions.¹⁷ The study identified the time within the therapeutic range (TTR) as a significant determinant for the development of in-stent thrombosis (IST). The cumulative incidence for in-stent thrombosis increased when the TTR fell below the threshold of 49.9% (p = .01); the specified TTR threshold value was 69.4% for patients treated with stenting in the acute phase and 45.9% for those treated for chronic post-thrombotic sequelae. However, it should be acknowledged that the patency rate after venous stenting depends on the pathology, inflow, hypercoagulable state, patient compliance, and other factors.

Other metanalyses and single-center studies have illustrated that in comparison with VKA, the exclusive use of low molecular weight heparins (LMWHs) in patients without endovascular interventions was associated with a reduction in PTS and venous ulceration, along with an enhancement in vein recanalization.¹⁸ Furthermore, a large single-center retrospective study reported that postinterventional therapy using solely LMWH (enoxaparin) had lower rates of in-stent restenosis compared with other anticoagulation regimens that transitioned from LMWH to VKA or direct oral anticoagulants (DOAC) at 1 month.¹⁹ Another retrospective study found that therapeutic anticoagulation with enoxaparin over 10 days after intervention correlated with significantly reduced odds of stent occlusion (OR = 0.034, 95% CI = [0.003–0.305], p = .004) compared to factor Xa inhibitors (OR = 0.417, 95% CI = [0.050, 2.793], p = .367) and warfarin (OR = 0.222, 95% CI = [0.020, 1.948], p = .183), during the early postprocedural phase.²⁰ While these data have yet to be confirmed in prospective venous stent trials, these findings have stimulated hypotheses that the anti-inflammatory effects of LMWHs could potentially optimize post-thrombotic outcomes with or without venous intervention.²¹ Although our study did not specifically investigate the effects of different types of anticoagulants, the LMWHs’ anti-inflammatory potential and their impact on post-thrombotic outcomes remain an area of interest for future research.

Many prior studies exclusively examined anticoagulants,^{9,11,14,15,17–20} and in cases where combination therapies were involved, the effect of anticoagulants compared to combination therapies was not well specified.^10,13,15,21 In contrast, we divided participants into three groups and analyzed their outcomes separately. About 62% (57/92) of patients in our study who underwent endovascular thrombus removal therapy with stent placement received combination therapy. This may indicate a distinctive approach at our center, potentially reflecting a growing recognition among clinicians of the potential benefits associated with combining antithrombotic treatments to enhance patient outcomes. Despite the current lack of clear consensus and evidence, our findings present an argument for exploring the utility of initial combination antithrombotic therapy following endovascular recanalization, thereby contributing to the broader discourse surrounding optimal anticoagulation approaches post-venous stent insertion. Although the role of antiplatelet therapy in patients with venous stenting remains uncertain in the literature, one study reported that combination therapy of anticoagulant and antiplatelet agents for patients with iliocaval stenting had a significant reduction in stent malfunction (HR = 0.23, CI = [0.08, 0.66], p = .07) at 12-month follow-up.¹⁸ A systemic review revealed that the incorporation of antiplatelet therapy (aspirin and clopidogrel) in patients with May-Thurner syndrome-related DVT after stent placement yielded higher rates of stent patency and event-free outcomes at 12 months, in comparison with treatment using anticoagulants alone (96% vs 80%).²¹ Another retrospective study indicated higher stent patency (HR = 0.28, CI = [0.10, 0.83],p = .022) in patients receiving concomitant antiplatelet and anticoagulation versus anticoagulation therapy alone.²² A second retrospective study examining triple therapy (anticoagulation with dual antiplatelet therapy [DAPT]) versus DAPT alone demonstrated reduced rates of in-stent restenosis (OR = 0.07, CI = [0.01, 0.53], p = .01), with four out of 52 patients (8%) in triple therapy experiencing major bleeding, compared to none in the DAPT alone group.²³ Specifically, patients who received triple antithrombotic therapy had significantly lower rates of stent restenosis compared to those with no antithrombotic therapy (OR = 0.05, p < .01), anticoagulation alone (OR = 0.19, p = .07), and dual antiplatelet therapy (OR = 0.25, p = .09).²⁴ One small case series of nine patients placed on rivaroxaban and once or twice daily clopidogrel for at least 6 months reported no in-stent restenosis or stent thrombosis within the 14-month follow-up periods.²⁵

While previous studies compared combination versus anticoagulants among patients after stent placement, our study focused on patients following all catheter-directed therapies. It is noteworthy to mention that even at the first follow-up visit of our study with an average duration of 38 days, the patency rates for both combination (59%) and anticoagulant (47%) groups were lower than those in studies on post-stenting patients, ranging from 70% to 96%.^21,22 This could be explained by different outcome definitions, different comorbidities, and event severity (extensive vein thrombosis vs nonthrombotic obstruction) requiring catheter-directed thrombus removal and stenting.

The optimal duration of anticoagulation therapy following stent placement is also unknown, with a limited number of studies addressing this issue. A survey of 106 vascular surgeons, interventional radiologists, and hematologists yielded a consensus: anticoagulation is generally preferred during the first 6–12 months following stenting, with lifelong anticoagulation reserved for individuals with a history of recurrent VTE or thrombophilia.²⁶ Another study of 113 patients who underwent stent placement showed no difference between anticoagulation durations of 3–12 months and that exceeding 12 months, implying that discontinuing anticoagulation within 3 to 12 months might be a reasonable approach in this patient population.²⁷

Several guidelines provide similar long-term anticoagulation recommendations. The 2021 American College of Chest Physicians (CHEST) guidelines recommend long-term anticoagulation beyond 3 months for patients with or at risk for recurrent VTE.²⁸ The 2023 European Society for Vascular Surgery (ESVS) recommends transitioning to antiplatelet therapy following 3 months of anticoagulation after thrombectomy or thrombolysis for acute DVT.²⁹ The National Institute for Health and Care Excellence (NICE) recommends anticoagulation treatment for at least 3 months for patients with confirmed proximal DVT, though without mentioning recommendations for those following interventions.³⁰ The Society for Vascular Surgery (SVS) 2012 guidelines recommend anticoagulation with unfractionated or low-molecular-weight heparin, followed by oral anticoagulants after catheter-based thrombus removal.³¹ The duration should be based on patient risk factors and CHEST guidelines, but the optimal anticoagulation length after the placement of the post-venous stent remains uncertain due to limited data.

Based on the current literature, our suggested antithrombotic approach for patients with acute DVT undergoing iliofemoral endovenous revascularization is summarized in Figure 3. For patients who undergo catheter-directed therapy with stenting, we recommend anticoagulation for 3–12 months, with a preference for DOAC or LMWH over VKA. In the case of patients at high risk for thrombosis, regardless of stent placement, we recommend LMWH for the first 30 days, followed by long-term anticoagulation. We suggest considering concurrent antiplatelet for 3–6 months for patients in both scenarios if they do not have a high risk for bleeding. For patients who receive catheter-directed therapy without stenting, we recommend anticoagulation for 3–12 months. We acknowledge that these recommendations are derived from the existing literature instead of robust head-to-head clinical trials.

Figure 3.

Chart of recommended antithrombotic therapies for patients with acute iliofemoral DVT following endovenous recanalization.

Study limitations

This study has several limitations that warrant consideration when interpreting its results. This retrospective review of medical records may introduce inconsistency, incomplete information, and inaccuracy in patient outcome assessment. The extraction of data relied on information documented in patient charts without means to validate its accuracy. It was hard to affirm complete patient compliance with the proposed treatment plan. This reliance on healthcare professionals accurately identifying, recording, and documenting patient-related information introduces a potential source of variability and inconsistency in the data.

This is a single-center study with a relatively modest sample size, especially in the antiplatelet therapy group and during the later follow-ups. This has constrained the statistical power to detect significant differences between groups. This limitation is particularly relevant in light of the observed trends in vein patency, re-thrombosis rates, and bleeding events that, while promising, did not attain statistical significance. There may also be a selection bias by involving the pediatric population in this study. Since data related to provoked versus unprovoked events or history of thrombophilia was not available for most patients, we were not able to address this patient population separately.

Another potential limitation pertains to the dynamic nature of patients’ therapeutic regimens, leading to changes in anticoagulation therapy type over time. Although efforts were made to categorize patients into specific therapy groups at each follow-up visit, therapeutic shifts may not have been captured comprehensively, potentially influencing the validity of the results. Furthermore, based on the current consensus, authors did not test patients for clopidogrel or aspirin response prior to initiating the antithrombotic therapy.

Conclusion

Our study revealed trends towards higher vein patency and less recurrent vein and stent thrombosis with an overall low number of major bleedings at first follow-up in patients receiving combination antithrombotic therapy, compared to those on anticoagulant or antiplatelet therapies. We recommend a multidisciplinary approach that would involve vascular surgery, vascular medicine, interventional radiology, and hematology specialists to provide optimal antithrombotic therapy recommendations based on current evidence considering the risk of thrombosis versus bleeding. While future studies with larger sample populations are needed to validate and further elucidate the subject, this study offers insight into the potential benefits of combination therapy in optimizing outcomes following endovascular intervention for acute DVT.

Footnotes

Acknowledgements

We would like to express our thanks to Minneapolis Heart Institute and Minneapolis Heart Institute Foundation for providing the necessary facilities and resources to conduct this research.

Author contributions

N.S., MD: Supervision, conceptualization, methodology, formal analysis, investigation, writing—original draft preparation. R.L.: Data curation, software, validation, writing—review and editing. E.C.: Formal analysis, data curation, writing—review and editing. B.E., MD: Investigation, writing—review and editing. J.M., MD: Investigation, writing—review and editing.

Declaration of conflicting interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) received no financial support for the research, authorship, and/or publication of this article.

Guarantor

Nedaa Skeik, MD, serves as the guarantor for this study and takes full responsibility for the integrity of the work.

Ethical statement

ORCID iDs

Nedaa Skeik

Rina Li

Appendix

Appendix 1.

Outcomes at all five (5) follow-ups for the adult-only study cohort.

Outcomes by Follow-Up Time
Characteristic	1, N = 116^a	2, N = 84^a	3, N = 55^a	4, N = 38^a	5, N = 16^a
Average follow-up time (days)	37 (30, 78)	140 (95, 248)	306 (191, 561)	674 (385, 803)	927 (585, 1582)
Patent	63 (54%)	54 (64%)	35 (64%)	25 (66%)	11 (69%)
Combination^b	35 (58%)	24 (60%)	8 (53%)	6 (55%)	4 (80%)
Anticoagulant^b	27 (53%)	23 (64%)	15 (63%)	8 (53%)	3 (75%)
Antiplatelet^b	1 (33%)	3 (100%)	7 (88%)	6 (100%)	2 (50%)
Vein/Stent thrombosis	57 (49%)	33 (39%)	22 (40%)	15 (39%)	7 (44%)
Combination^b	27 (45%)	17 (43%)	7 (47%)	6 (55%)	2 (40%)
Anticoagulant^b	25 (49%)	15 (42%)	11 (46%)	8 (53%)	2 (50%)
Antiplatelet^b	3 (100%)	0 (0%)	1 (13%)	0 (0%)	2 (50%)
Major bleeding	6 (5.2%)	3 (3.6%)	4 (7.3%)	1 (2.6%)	1 (6.3%)
Combination^b	2 (3.3%)	1 (2.5%)	0 (0%)	0 (0%)	0 (0%)
Anticoagulant^b	4 (7.8%)	2 (5.6%)	4 (17%)	0 (0%)	0 (0%)
Antiplatelet^b	0 (0%)	0 (0%)	0 (0%)	0 (0%)	1 (25%)

^aMedian (IQR); n (%).

^bFrequencies based on proportion of people that experience the outcome within each therapy group.

Appendix 2.

Outcomes at all five (5) follow-ups for the study cohort, including both adults and minors.

Outcomes by Follow-Up Time
Characteristic	1, N = 128^a	2, N = 92^a	3, N = 62^a	4, N = 43^a	5, N = 21^a
Average follow-up time (days)	38 (30, 80)	141 (95, 265)	307 (182, 658)	688 (381, 837)	1351 (718, 1692)
atent	66 (52%)	57 (62%)	37 (60%)	26 (60%)	13 (62%)
Combination^b	37 (59%)	26 (59%)	9 (53%)	6 (50%)	5 (71%)
Anticoagulant^b	28 (47%)	24 (60%)	16 (55%)	9 (47%)	4 (67%)
Antiplatelet^b	1 (25%)	3 (100%)	7 (88%)	6 (100%)	2 (40%)
Vein/Stent thrombosis	67 (52%)	39 (42%)	28 (45%)	20 (47%)	11 (52%)
Combination^b	29 (46%)	19 (43%)	8 (47%)	7 (58%)	3 (43%)
Anticoagulant^b	32 (54%)	19 (48%)	16 (55%)	12 (63%)	4 (67%)
Antiplatelet^b	4 (100%)	0 (0%)	1 (13%)	0 (0%)	3 (60%)
Major bleeding	6 (4.7%)	3 (3.3%)	4 (6.5%)	1 (2.3%)	1 (4.8%)
Combination^b	2 (3.2%)	1 (2.3%)	0 (0%)	0 (0%)	0 (0%)
Anticoagulant^b	4 (6.8%)	2 (5.0%)	4 (14%)	0 (0%)	0 (0%)
Antiplatelet^b	0 (0%)	0 (0%)	0 (0%)	0 (0%)	1 (20%)

^aMedian (IQR); n (%).

^bfrequencies based on proportion of people that experience the outcome within each therapy group.

References

Kearon

Ageno

Cannegieter

, et al. Categorization of patients as having provoked or unprovoked venous thromboembolism: guidance from the SSC of ISTH. J Thromb Haemost 2016; 14(7): 1480–1483.

Raskob

Silverstein

Bratzler

, et al. Surveillance for deep vein thrombosis and pulmonary embolism: recommendations from a national workshop. Am J Prev Med 2010; 38(4 Suppl): S502–S509.

Lookstein

Giordano

. Deep vein thrombosis: endovascular management. Mt Sinai J Med 2010; 77(3): 286–295.

Kearon

Akl

Ornelas

, et al. Antithrombotic therapy for VTE disease: CHEST guideline and expert panel report. Chest 2016; 149(2): 315–352.

Jia

Alexander

Skeik

. May-thurner syndrome with large abdominal varicosity, treated successfully using multiple approaches. Case Rep Vasc Med 2019; 2019: 7079307.

Joh

Desai

. Treatment of nonthrombotic iliac vein lesions. Semin Interv Radiol 2021; 38(2): 155–159.

Mousa

AbuRahma

. May-Thurner syndrome: update and review. Ann Vasc Surg 2013; 27(7): 984–995.

Brazeau

Harvey

Pinto

, et al. May-Thurner syndrome: diagnosis and management. Vasa 2013; 42(2): 96–105.

Hölper

Kotelis

Attigah

, et al. Longterm results after surgical thrombectomy and simultaneous stenting for symptomatic iliofemoral venous thrombosis. Eur J Vasc Endovasc Surg 2010; 39(3): 349–355.

10.

Xiao

Desai

. Antithrombotic therapy after venous stent placement. Vas Endova Rev. 2020; 3: e10.

11.

Meissner

Caps

Bergelin

, et al. Propagation, rethrombosis and new thrombus formation after acute deep venous thrombosis. J Vasc Surg 1995; 22(5): 558–567.

12.

Franco

Becattini

Beyer-Westendorf

, et al. Definition of major bleeding: prognostic classification. J Thromb Haemost 2020; 18(11): 2852–2860.

13.

Eijgenraam

ten Cate

ten Cate-Hoek

. Venous stenting after deep venous thrombosis and antithrombotic therapy: a systematic review. Reviews in Vascular Medicine 2014; 2: 88–97.

14.

Razavi

Jaff

Miller

. Safety and effectiveness of stent placement for iliofemoral venous outflow obstruction: systematic review and meta-analysis. Circ Cardiovasc Interv 2015; 8(10): e002772.

15.

Notten

Ten Cate

Ten Cate-Hoek

. Postinterventional antithrombotic management after venous stenting of the iliofemoral tract in acute and chronic thrombosis: a systematic review. J Thromb Haemost 2021; 19(3): 753–796.

16.

Sebastian

Hakki

Spirk

, et al. Rivaroxaban or vitamin-K antagonists following early endovascular thrombus removal and stent placement for acute iliofemoral deep vein thrombosis. Thromb Res 2018; 172: 86–93.

17.

Notten

van Laanen

JHH

Eijgenraam

, et al. Quality of anticoagulant therapy and the incidence of in-stent thrombosis after venous stenting. Res Pract Thromb Haemost 2020; 4(4): 594–603.

18.

Kishore

Khaja

Thornburg

, et al. Antithrombotic therapy after venous interventions: AJR expert panel narrative review. AJR Am J Roentgenol 2022; 219(2): 175–187.

19.

Mabud

Cohn

Arendt

, et al. Lower extremity venous stent placement: a large retrospective single-center analysis. J Vasc Interv Radiol 2020; 31(2): 251–259.

20.

Marston

Browder

Iles

, et al. Early thrombosis after iliac stenting for venous outflow occlusion is related to disease severity and type of anticoagulation. J Vasc Surg Venous Lymphat Disord 2021; 9(6): 1399–1407.

21.

Parnos

Garcia

. May-Thurner syndrome and thrombosis: a systematic review of antithrombotic use after endovascular stent placement. Res Pract Thromb Haemost 2019; 3(1): 70–78.

22.

Endo

Jahangiri

Horikawa

, et al. Antiplatelet therapy is associated with stent patency after iliocaval venous stenting. Cardiovasc Interv Radiol 2018; 41(11): 1691–1698.

23.

Lin

Martin

Wang

, et al. Long-term antithrombotic therapy after venous stent placement. Phlebology 2020; 35(6): 402–408.

24.

Lin

Martin

Wang

, et al. Long-term antithrombotic therapy after venous stent placement. Blood 2018; 132(Supplement 1): 1249.

25.

Langwieser

Bernlochner

Wustrow

, et al. Combination of factor Xa inhibition and antiplatelet therapy after stenting in patients with iliofemoral post-thrombotic venous obstruction. Phlebology 2016; 31(6): 430–437.

26.

Milinis

Thapar

Shalhoub

, et al. Antithrombotic therapy following venous stenting: international delphi consensus. Eur J Vasc Endovasc Surg 2018; 55(4): 537–544.

27.

Sebastian

Engelberger

Spirk

, et al. Cessation of anticoagulation therapy following endovascular thrombus removal and stent placement for acute iliofemoral deep vein thrombosis. Vasa 2019; 48(4): 331–339.

28.

Stevens

Woller

Baumann Kreuziger

, et al. Executive summary: antithrombotic therapy for VTE disease: second update of the CHEST guideline and expert panel report. Chest 2021; 160(6): 2247–2259.

29.

Twine

Kakkos

Aboyans

, et al. Editor’s choice – European society for vascular surgery (ESVS) 2023 clinical practice guidelines on antithrombotic therapy for vascular diseases. Eur J Vasc Endovasc Surg 2023; 65(5): 627–689.

30.

(NICE) NIfHaCE . National Institute for Health and care excellence: clinical guidelines. Venous thromboembolic diseases: diagnosis, management and thrombophilia testing. London2023.

31.

Meissner

Gloviczki

Comerota

, et al. Early thrombus removal strategies for acute deep venous thrombosis: clinical practice guidelines of the Society for Vascular Surgery and the American Venous Forum. J Vasc Surg 2012; 55(5): 1449–1462.