Rationale and design of the DEFIANCE study: A randomized controlled trial of mechanical thrombectomy versus anticoagulation alone for iliofemoral deep vein thrombosis.

Deep vein thrombosis (DVT) is a common medical condition that is associated with clinically significant sequelae, including postthrombotic syndrome (PTS). Anticoagulation alone remains the guideline-recommended treatment for many patients with iliofemoral DVT. Recent technological advances have led to an increase in the use of mechanical thrombectomy for DVT, but mechanical thrombectomy-based procedures have not yet been compared with standard-of-care anticoagulation therapy in randomized studies. The DEFIANCE study (ClinicalTrials.gov: NCT05701917) is an international and actively enrolling randomized controlled trial (RCT) in lower extremity DVT assessing an interventional strategy that includes mechanical thrombectomy with the ClotTriever System (Inari Medical, Irvine, CA) versus anticoagulation alone. Approximately 300 patients with unilateral iliofemoral DVT and symptom duration ≤ 12 weeks will be randomized 1:1. Study conduct includes an independent core laboratory for duplex ultrasound assessment, an independent medical monitor for safety adjudication, and evaluation of PTS severity on the Villalta scale using best clinical practices. The primary endpoint is a composite outcome structured as a hierarchal win ratio of 1) the occurrence of treatment failure or therapy escalation as adjudicated by the medical monitor, with failure defined as amputation or gangrene of the target leg or venous thromboembolism-related mortality, and 2) the assessment of PTS severity at the 6-month follow-up visit. In addition to being a component of the primary endpoint, the severity of PTS at 6 months is also evaluated as a stand-alone secondary endpoint. An additional secondary endpoint is a composite of outcomes at the 10-day visit and is structured as a hierarchal win ratio of 1) vessel compressibility on duplex ultrasound, 2) patient-reported pain, and 3) improvement of edema. The safety endpoints are access site complications requiring endovascular or surgical repair and the occurrence through the 30-day visit of mortality, major bleeding, or new symptomatic pulmonary embolism. DEFIANCE will be the first RCT to evaluate a mechanical thrombectomy-based interventional approach versus anticoagulation therapy alone for DVT. The results will inform the treatment of patients with iliofemoral DVT and the prevention of PTS-associated morbidity. DEFIANCE: RCT of ClotTriever System Versus Anticoagulation In Deep Vein Thrombosis (DEFIANCE), ClinicalTrials.gov: NCT05701917, URL: https://clinicaltrials.gov/study/NCT05701917?cond=Deep%20Vein%20Thrombosis&term=defiance&rank=1.

Abramowitz SD ，Marko X ，D'Souza D ，Noor S ，Pereira K ，Silver MJ ，Rosenberg SP ，Markovitz CD ，Tu T ，Weinberg I ，Black S ... -  《-》

Comparison of anticoagulation vs mechanical thrombectomy for the treatment of iliofemoral deep vein thrombosis.

To compare the comparative effects of treatment with contemporary mechanical thrombectomy (MT) or anticoagulation (AC) on Villalta scores and post-thrombotic syndrome (PTS) incidence through 12 months in iliofemoral deep vein thrombosis (DVT). Patients with DVT in the Acute Venous Thrombosis: Thrombus Removal with Adjunctive Catheter-Directed Thrombolysis (ATTRACT) randomized trial and the ClotTriever Outcomes (CLOUT) registry were included in this analysis. Both studies evaluated the effects of thrombus removal on the incidence of PTS. Patients with bilateral DVT, isolated femoral-popliteal DVT, symptom duration of >4 weeks, or incomplete case data for matching covariates were excluded. Propensity scores were used to match patients 1:1 who received AC (from ATTRACT) with those treated with mechanical thrombectomy (from CLOUT) using nearest neighbor matching on nine baseline covariates, including age, body mass index, leg treated, provoked DVT, prior venous thromboembolism, race, sex, Villalta score, and symptom duration. Clinical outcomes, including Villalta score and PTS, were assessed. Logistic regression was used to estimate the likelihood of developing PTS at 12 months. A total of 164 pairs were matched, with no significant differences in baseline characteristics after matching. There were fewer patients with any PTS at 6 months (19% vs 46%; P < .001) and 12 months (17% vs 38%; P < .001) in the MT treatment group. Modeling revealed that, after adjusting for baseline Villalta scores, patients treated with AC had significantly higher odds of developing any PTS (odds ratio, 3.1; 95% confidence interval, 1.5-6.2; P = .002) or moderate to severe PTS (odds ratio, 3.1; 95% confidence interval, 1.1-8.4; P = .027) at 12 months compared with those treated with MT. Mean Villalta scores were lower through 12 months among those receiving MT vs AC (3.3 vs 6.3 at 30 days, 2.5 vs 5.5 at 6 months, and 2.6 vs 4.9 at 12 months; P < .001 for all). MT treatment of iliofemoral DVT was associated with significantly lower Villalta scores and a lower incidence of PTS through 12 months compared with treatment using AC. Results from currently enrolling clinical trials will further clarify the role of these therapies in the prevention of PTS after an acute DVT event.

Abramowitz S ，Shaikh A ，Mojibian H ，Mouawad NJ ，Bunte MC ，Skripochnik E ，Lindquist J ，Elmasri F ，Khalsa B ，Bhat A ，Nguyen J ，Shah N ，Noor SS ，Murrey D ，Gandhi S ，Raskin A ，Schor J ，Dexter DJ ... -  《-》

Angioplasty or stenting for deep venous thrombosis.

The best medical treatment (BMT) for treating deep venous thrombosis (DVT) includes anticoagulation and compression stockings. Angioplasty and stenting restore vessel patency and facilitate blood flow. In some people with DVT, angioplasty or stenting is used to minimise complications such as post-thrombotic syndrome (PTS), but their effects are under discussion. To assess the effects of adjunctive angioplasty or stenting on a background treatment of anticoagulation and thrombolysis, compared with BMT, sham procedure, thrombolysis, or any combination of these treatments, in people with DVT. We searched CENTRAL, MEDLINE, Embase, LILACS, IBECS, CINAHL, and AMED databases, as well as the World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov trials registers, to 20 April 2023. We checked the bibliographies of included trials for further references to relevant trials and contacted specialists in the field, manufacturers, and authors of the included trials for any unpublished data. We included randomised controlled trials (RCTs) comparing angioplasty or stenting on a background treatment of anticoagulation and thrombolysis, compared with BMT, sham procedure, thrombolysis, or any combination of these treatments, in the management of people with acute obstruction due to DVT. We excluded participants who had a baseline PTS diagnosis or who had received any form of mechanical thrombectomy, as this was investigated in a separate Cochrane review. We used standard Cochrane methods. The primary outcomes were PTS and venous thromboembolism (VTE); secondary outcomes were mortality, major bleeding, secondary patency, duration of hospitalisation, quality of life (QoL), and adverse events. We used the Cochrane RoB 1 tool to assess the risk of bias for RCTs and GRADE to assess the certainty of evidence. We performed meta-analysis where appropriate. We included two RCTs (134 participants) that were conducted in China and presented comparisons for acute obstruction after DVT based on length of follow-up (12 months (early), 24 months (intermediate), and 36 months (long term)). Angioplasty or stenting plus BMT and thrombolysis versus BMT and thrombolysis for acute obstruction due to DVT (intermediate time point) In the intermediate time point, angioplasty or stenting may have little to no effect on PTS (Venous Clinical Severity Score (VCSS): mean difference (MD) -3.21, 95% confidence interval (CI) -7.74 to 1.33; 2 studies, 133 participants; very low-certainty evidence) and adverse events (limb pain) (risk ratio (RR) 0.68, 95% CI 0.04 to 10.33; 1 study, 67 participants; very low-certainty evidence), but the evidence is very uncertain. Angioplasty or stenting may increase secondary patency (RR 0.26, 95% CI 0.11 to 0.59; 2 studies, 133 participants; very low-certainty evidence), but the evidence is very uncertain. The evidence is very uncertain about the effect of angioplasty or stenting on quality of life (MD 10.54, 95% CI -1.34 to 22.41; 2 studies, 133 participants; very low-certainty evidence), and is not estimable for VTE, mortality, or major bleeding. We downgraded the certainty of evidence for all reported outcomes in this comparison by two levels due to serious study limitations (risk of performance and other bias), and another level for imprecision (small numbers of events and participants). The imbalance between study group size and different vein access may also have contributed to the high heterogeneity seen in the analyses of these outcomes. We downgraded the certainty of evidence for PTS and quality of life by one level for inconsistency (no similarity of point estimates in any of the included studies, no overlap of CIs, and considerable heterogeneity in results). There is an additional difficulty with blinding personnel in this type of intervention, but the trialists should have reported blinding of outcome assessment. Although angioplasty or stenting may increase secondary patency in people with acute obstruction due to DVT, the evidence is very uncertain; the evidence is also very uncertain about the effect of angioplasty or stenting on PTS, quality of life, and adverse events in people with acute obstruction due to DVT. The effects on VTE, mortality, and major bleeding were not estimable or not assessed by the included studies. Future trials must be large enough to detect significant clinical outcomes, and provide data on original stenosis before angioplasty or stenting and differing times from the initial event, among other essential characteristics.

Flumignan RL ，Nakano LC ，Flumignan CD ，Baptista-Silva JC ... -  《-》

Single-session mechanical thrombectomy for iliofemoral deep vein thrombosis using a dual mechanism of action device combining basket and rotational thrombectomy.

Interventional treatments for acute iliofemoral deep vein thrombosis (DVT) remain controversial after publication of the Acute Venous Thrombosis: Thrombus Removal with Adjunctive Catheter-Directed Thrombolysis (ATTRACT) study. Interventions have been shown to reduce post-thrombotic syndrome severity and improve quality of life in DVT patients, but have been accompanied by risk of major bleeding from thrombolytics. We describe thrombus removal using a novel combined basket-rotational thrombectomy device that minimizes the need for thrombolytics or repeat procedures. The aim of this prospective, nonrandomized, multicenter, first-in-human study of 19 patients with acute iliofemoral DVT was to evaluate the safety and performance of the Pounce venous thrombectomy system ≤12 months after treatment. The primary performance end point was defined as procedural success through achievement of Society of Interventional Radiology (SIR) grade II lysis in treated vessels with freedom from procedural adverse events. Secondary end points included venous disease severity assessments using the Villalta scale and the Venous Clinical Severity Score, patient quality-of-life measurement using the Venous Insufficiency Epidemiological and Economic Study-Quality of Life questionnaire, and calf circumference measurements taken at baseline, 24 hours, and 1 month. The primary end point of complete or near-complete thrombus removal (Society of Interventional Radiology grade II or III) was achieved in all patients. All study device-related safety end points were met, with no major bleeding or device-related adverse events. Of the 19 patients treated, 16 (84.2%) did not receive thrombolytics during the procedure. Post-thrombotic syndrome (Villalta scale >4) was identified in 17 of 19 patients (89.5%) at baseline, 4 of 13 patients (30.8%) available for follow-up at 6 months, and 2 of 11 patients (18.2%) at 12 months. The median Venous Clinical Severity Score decreased (P < .001) from 8.5 (interquartile range [IQR], 7-10) at baseline to 4 (IQR, 2-4) at 1 month after the procedure and was similar at 6 months (2; IQR, 2-5) and 12 months (2; IQR, 1.5-3) after the procedure. The median Venous Insufficiency Epidemiological and Economic Study-Quality of Life questionnaire score improved (P < .001) by 39 from baseline (57; IQR, 53.5-74) to 1 month (96; IQR, 86-101) after the procedure, and remained high at 6 months (99; IQR, 75-103) and 12 months (98; IQR, 94.5-100). The median calf circumference decreased (P = .089) from 39 cm (IQR, 35-47.8 cm) at baseline to 36 cm (IQR, 32.5-40.5 cm) at 24 hours after the procedure and was 34.5 cm (IQR, 33.2-38.5 cm) at 1 month. The Pounce device is safe and effective for removal the of thrombus in patients with acute iliofemoral DVT. Initial results demonstrate improvements in venous disease severity and patient quality of life.

Black SA ，Thulasidasan N ，Benton L ，O'Sullivan GJ ，Konteva M ，Petrov IS ，Walsh SR ，Lichtenberg M ... -  《-》

Assessing the Predictive Value of the Neutrophil-to-Lymphocyte Ratio for Post-Thrombotic Syndrome following Iliofemoral Deep Venous Thrombosis.

Post-thrombotic syndrome (PTS) is a common complication of deep vein thrombosis (DVT) that occurs in 20-50% of patients and results in a decreased quality of life. Even with the progressive identification of PTS risk factors, clinically useful predictors of PTS continue to be limited, unobjective, and ill-defined. The neutrophil-to-lymphocyte ratio (NLR) is an emerging prognostic biomarker used in a variety of diseases that reflects acute systemic inflammation. This pilot study aimed to evaluate the utility of the NLR at the time of iliofemoral DVT diagnosis in predicting PTS incidence in patients. A retrospective chart review was performed on patients identified with iliofemoral DVT at the University of Maryland Medical Center between 2020 and 2022. Patients with at least one follow-up visit between 3 and 6 months after initial DVT diagnosis were included. Diagnosis of PTS was determined based on Villalta Score. The Youden index with receiver operating characteristic curve analysis was used to determine the NLR cut-off value that may be predictive of PTS. A multivariable logistic regression model was then performed to assess the utility of this NLR cut-off value and other common clinical markers in predicting the presence of PTS symptoms. Four hundred and eighteen patients with positive iliofemoral DVT venous duplex ultrasounds were screened for eligibility. One hundred and eighteen patients were eligible with a mean age of 53.18 ± 15.45 years. A total of 43 patients (36.44%) were found to have PTS. An NLR cut-off of 7.71 was determined with an area under the receiver operating characteristic curve (area under the curve) of 0.63 (P = 0.046). When the NLR was assessed jointly with other clinical markers at the time of DVT diagnosis, NLR was a statistically significant positive predictor, measured using odds ratio (1.83; 95% confidence interval, 1.20-2.78; P = 0.005). Our study found that when stratified by a determined cutoff value, the NLR at the time of DVT diagnosis was significantly associated with the development of PTS in patients with iliofemoral DVT. This result is consistent with one prior research finding yet is novel in its specificity for iliofemoral DVTs and its acute lab collection for NLR calculation. The NLR should be further investigated as a potential inexpensive prognostic tool to aid in the improvement of treatment and prophylactic strategies for PTS.

DeMartino AG ，Chatterjee D ，De Ravin L ，Babick O ，Shiva A ，Shah N ，Nagarsheth K ... -  《-》