Five-Year Outcomes of the SuperB Trial: A Multicenter Randomized Controlled Trial Comparing Heparin-Bonded Endograft to Surgical Femoropopliteal Bypass.

OBJECTIVE: This study aims to compare the 5-year outcomes of endoluminal bypass (EB) using heparin-bonded self-expanding covered stents versus bypass surgery for extensive femoropopliteal disease, including technical and clinical outcomes and health status. BACKGROUND: The surgical femoropopliteal bypass was the gold standard to treat peripheral arterial disease (PAD) for decades; however, endovascular treatment modalities are now recommended for most femoropopliteal lesions. One-year data of a randomized controlled trial comparing EB with surgical bypass (SB) have shown a faster recovery, less morbidity, and comparable patency rates between the two techniques. To date, long-term randomized controlled data regarding both techniques are lacking. METHODS: Five-year results of a multicenter randomized controlled trial comparing EB with SB in patients with femoropopliteal artery disease were evaluated based on intention-to-treat and per-protocol analyses. RESULTS: At 5-year follow-up, primary, primary-assisted, and secondary patency rates were 36.2%, 52.4%, and 68.1% for EB and 49.4%, 72.2%, and 77.8% for SB, respectively (p=0.608). Freedom from target lesion revascularization (fTLR) was 34.1% for EB and 57.6% for SB (p=0.365). In both groups, the ankle-brachial index, Rutherford classification, and walking distance significantly improved compared with baseline without differences between groups at follow-up. Freedom from major amputation rate was 92.6% in the EB group and 96.2% in the SB group (p=0.361). The 36-Item Short-Form Health Survey showed no significant differences between groups. CONCLUSION: Treatment of extensive femoropopliteal disease with self-expanding covered stents provides comparable clinical-related and health-related questionnaire outcomes when compared with SB through 5 years of follow-up. However, the EB is related to a higher number of reinterventions. CLINICAL IMPACT: This present study is the first to report five-year outcomes comparing an endoluminal (EB) using heparin-bonded self-expanding covered stents with surgical bypass (SB) for long and complex femoropopliteal disease. Although the advantages of treatment with EB are mostly seen in the early period after treatment, the outcomes support the use of EB for this indication and seems to be a valid and safe alternative for bypass surgery. Future trials comparing various endovascular strategies may provide further guidance for the development of an evidence-based treatment algorithm.

Clinical impact of assessing thrombus age using magnetic resonance venography prior to catheter-directed thrombolysis.

OBJECTIVES: Magnetic resonance venography (MRV) is underutilized in the evaluation of thrombus properties prior to endovascular treatment but may improve procedural outcomes. We therefore investigated the clinical impact of using a dedicated MRV scoring system to assess thrombus characteristics prior to endovascular intervention for iliofemoral deep vein thrombosis (DVT). METHODS: This is a post hoc analysis of data from the CAVA trial ( Clinicaltrials.gov :NCT00970619). MRV studies of patients receiving ultrasound-accelerated catheter-directed thrombolysis (CDT) for iliofemoral DVT were reviewed. Thrombus age-related imaging characteristics were scored and translated into an overall score (acute, subacute, or old). MRV scores were compared to patient-reported complaints. MRV-scored groups were compared for CDT duration and success rate. RESULTS: Fifty-six patients (29 men; age 50.8 ± 16.4 years) were included. Using MRV, 27 thrombi were classified acute, 17 subacute, and 12 old. Based on patient-reported complaints, 11 (91.7%) of these old thrombi would have been categorized acute or subacute, and one (3.7%) of the acute thrombi as old. Average duration of CDT to > 90% restored patency differed significantly between groups (p < 0.0001): average duration was 23 h for acute thromboses (range: 19-25), 43 h for subacute (range: 41-62), and 85 h for old thromboses (range: 74-96). CDT was almost eleven times more successful in thromboses characterized as acute and subacute compared to old thromboses (OR: 10.7; 95% CI 2.1-55.5). CONCLUSION: A dedicated MRV scoring system can safely discriminate between acute, subacute, and old thromboses. MRV-based selection is predictive of procedural duration and success rate and can help avoid unnecessary complications. KEY POINTS: • Thrombus age, characterized by MRV as acute, subacute, and old, can predict CDT duration and probability of success. • Accurate pre-interventional MRV-based thrombus aging has the potential to facilitate identification of eligible patients and may thus prevent CDT-related complications.

CAVA (Ultrasound-Accelerated Catheter-Directed Thrombolysis on Preventing Post-Thrombotic Syndrome) Trial: Long-Term Follow-Up Results.

Background The CAVA (Ultrasound-Accelerated Catheter-Directed Thrombolysis Versus Anticoagulation for the Prevention of Post-Thrombotic Syndrome) trial did not show a reduction of post-thrombotic syndrome (PTS) after additional ultrasound-accelerated catheter-directed thrombolysis in patients with acute iliofemoral deep vein thrombosis at 1-year follow-up. This prespecified analysis of the CAVA trial aimed to determine the impact of additional thrombolysis on outcomes of PTS at long-term follow-up. Methods and Results Patients aged 18 to 85 years with a first-time acute iliofemoral deep vein thrombosis were included and randomly assigned (1:1) to either standard treatment plus ultrasound-accelerated catheter-directed thrombolysis or standard treatment alone. The primary outcome was the proportion of PTS (Villalta score ≥5 on 2 occasions ≥3 months apart or venous ulceration) at the final follow-up visit. Additionally, PTS according to the International Society on Thrombosis and Haemostasis (ISTH) consensus definition was assessed to allow external comparability. Major bleedings were the main safety outcome. At a median follow-up of 39.0 months (interquartile range, 23.3-63.8), 120 patients (79.8%) participated in the final follow-up visit: 62 from the intervention group and 58 from the standard treatment group. PTS developed in 19 (30.6%) versus 26 (44.8%) patients, respectively (odds ratio [OR], 0.54; 95% CI, 0.26 to 1.15 [P=0.11]), with an absolute difference between groups of -14.2% (95% CI, -32.0% to 4.8%). Using the ISTH consensus definition, a significant reduction in PTS was observed (29 [46.8%] versus 40 [69.0%]) (OR, 0.40; 95% CI, 0.19-0.84 [P=0.01]) with an absolute difference between groups of -22.2% (95% CI, -39.8% to -2.8%). No new major bleedings occurred following the 12-month follow-up. Conclusions The impact of additional ultrasound-accelerated catheter-directed thrombolysis on the prevention of PTS was found to increase with time. Although this study was limited by its sample size, the overall findings indicate a reduction of mild PTS without impact on quality of life. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT00970619.

Association of Successful Ultrasound-Accelerated Catheter-Directed Thrombolysis with Postthrombotic Syndrome: A Post Hoc Analysis of the CAVA Trial.

BACKGROUND: The CAVA trial did not show the anticipated risk reduction for postthrombotic syndrome (PTS) after thrombus removal via additional ultrasound-accelerated catheter-directed thrombolysis (UACDT) in patients with acute iliofemoral deep vein thrombosis (IFDVT). Difficulties in achieving an effective degree of recanalization through thrombolysis may have influenced outcomes. We therefore assessed whether successful UACDT (restored patency ≥ 90%) did reduce the development of PTS. METHODS: This CAVA trial post hoc analysis compared the proportion of PTS at 1-year follow-up between patients with successful UACDT and patients that received standard treatment only. In addition, clinical impact as well as determinants of successful thrombolysis were explored. RESULTS: UACDT was initiated in 77 (50.7%) patients and considered successful in 41 (53.2%, interrater agreement κ = 0.7, 95% confidence interval 0.47-0.83). PTS developed in 15/41 (36.6%) patients in the successful UACDT group versus 33/75 (44.0%) controls (p = 0.44). In this comparison, successful UACDT was associated with lower Venous Clinical Severity Score (3.50 ± 2.57 vs. 4.82 ± 2.74, p = 0.02) and higher EuroQOL-5D (EQ-5D) scores (40.2 ± 36.4 vs. 23.4 ± 34.4, p = 0.01). Compared with unsuccessful UACDT, successful UACDT was associated with a shorter symptom duration at inclusion (p = 0.05), and higher rates of performed adjunctive procedures (p < 0.001) and stent placement (p < 0.001). CONCLUSION: Successful UACDT was not associated with a reduced proportion of PTS 1 year after acute IFDVT compared with patients receiving standard treatment alone. There was, however, a significant reduction in symptom severity and improvement of generic quality of life according to the EQ-5D. Better patient selection and optimization of treatment protocols are needed to assess the full potential of UACDT for the prevention of PTS. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov number, NCT00970619.

Ultrasound-accelerated catheter-directed thrombolysis versus anticoagulation for the prevention of post-thrombotic syndrome (CAVA): a single-blind, multicentre, randomised trial.

BACKGROUND: Early thrombus removal might prevent post-thrombotic syndrome by preserving venous function and restoring flow. Previous trials comparing additional catheter-directed thrombolysis to standard treatment showed conflicting outcomes. We aimed to assess the benefit of additional ultrasound-accelerated catheter-directed thrombolysis for the prevention of post-thrombotic syndrome compared with standard therapy in patients with iliofemoral deep-vein thrombosis. METHODS: We did a multicentre, randomised, single-blind, allocation-concealed, parallel group, superiority trial in 15 hospitals in the Netherlands. Patients aged 18-85 years with a first-time acute iliofemoral deep-vein thrombosis and symptoms for no more than 14 days were randomly assigned (1:1) to either standard treatment with additional ultrasound-accelerated catheter-directed thrombolysis or standard treatment alone. Randomisation was done with a web-based automatic programme and a random varying block size (2-12), stratified by age and centre. Standard treatment included anticoagulant therapy, compression therapy (knee-high elastic compression stockings; 30-40 mmHg), and early ambulation. Additional ultrasound-accelerated catheter-directed thrombolysis was done with urokinase with a starting bolus of 250 000 international units (IU) in 10 mL NaCl followed by a continuous dose of 100 000 IU/h for a maximum of 96 h through the Ekos Endowave-system. Adjunctive percutaneous transluminal angioplasty, thrombosuction, or stenting was performed at the discretion of the physician who performed the intervention. The primary outcome was the proportion of patients with post-thrombotic syndrome at 12 months diagnosed according to the original Villalta criteria-a Villalta-score of at least 5 on two consecutive occasions at least 3 months apart or the occurrence of venous ulceration-and was assessed in a modified intention-to-treat population of all randomly assigned patients who passed screening and started treatment. The safety analysis was assessed in the same modified intention-to-treat population. This study is complete and is registered at ClinicalTrials.gov, NCT00970619. FINDINGS: Between May 28, 2010, and Sept 18, 2017, 184 patients were randomly assigned to either additional ultrasound-accelerated catheter-directed thrombolysis (n=91) or standard treatment alone (n=93). Exclusion because of screening failure or early withdrawal of informed consent resulted in 77 patients in the intervention group and 75 in the standard treatment group starting allocated treatment. Median follow-up was 12·0 months (IQR 6·0-12·0). 12-month post-thrombotic syndrome occurred in 22 (29%) patients allocated to additional treatment versus 26 (35%) patients receiving standard treatment alone (odds ratio 0·75 [95% CI 0·38 to 1·50]; p=0·42). Major bleeding occurred in four (5%) patients in the intervention group, with associated neuropraxia or the peroneal nerve in one patient, and no events in the standard treatment group. No serious adverse events occurred. None of the four deaths (one [1%] in the intervention group vs three [4%] in the standard treatment group) were treatment related. INTERPRETATION: This study showed that additional ultrasound-accelerated catheter-directed thrombolysis does not change the risk of post-thrombotic syndrome 1 year after acute iliofemoral deep-vein thrombosis compared with standard therapy alone. Although this trial is inconclusive, the outcome suggests the possibility of a moderate beneficial effect with additional ultrasound-accelerated catheter-directed thrombolysis. Further research is therefore warranted to better understand this outcome in the context of previous trials, preferably by combining the available evidence in an individual patient data meta-analysis. FUNDING: The Netherlands Organisation for Health Research and Development (ZonMw), Maastricht University Medical Centre, BTG-Interventional Medicine.

1-Year Results of a Multicenter Randomized Controlled Trial Comparing Heparin-Bonded Endoluminal to Femoropopliteal Bypass.

OBJECTIVES: This study sought to compare heparin-bonded endografts with femoropopliteal bypass, including quality of life, using general health and disease-specific questionnaires as well as patency rates. BACKGROUND: Endovascular treatment continues to advance and is gaining acceptance as primary treatment for long occlusive or stenotic lesions in the superficial femoral artery. Heparin-bonded expanded polytetrafluoroethylene endografts have been related to outcomes comparable to bypass surgery, but this has not been tested in a randomized fashion. METHODS: A multicenter randomized-controlled trial was performed comparing femoropopliteal bypass with heparin-bonded expanded polytetrafluoroethylene endografts. Data were analyzed on an intention-to-treat and per-protocol manner. RESULTS: A total of 129 patients were randomized and 125 patients were treated, 63 in the endoluminal and 62 in the surgical group (42 venous, 20 prosthetic). Enrollment was terminated before reaching the predefined target number for patency. Baseline characteristics and anatomical data were similar. Patients were treated for critical limb ischemia in 38.1% and 32.2% in the endoluminal and surgical arms, respectively. Mean lesion length was 23 cm in both groups and lesions were largely TransAtlantic Inter-Society Consensus II D. Hospitalization time and 30-day morbidity were significantly lower in the endoluminal group, without differences in serious adverse events (n = 5 each; surgical: 4 venous and 1 polytetrafluoroethylene bypass). There were no significant differences in Rutherford category between groups at any time point. At 30 days the endoluminal group showed a greater improvement in quality-of-life scores. At 1 year, these differences had largely disappeared and no differences in primary (endoluminal: 64.8%; surgical: 63.6%), assisted primary (endoluminal: 78.1%; surgical: 79.8%), secondary patency (endoluminal: 85.9%; surgical: 83.3%), and target vessel revascularization (endoluminal: 72.1%; surgical: 71.0%) were observed. Limb salvage rate was 100% in both groups. CONCLUSIONS: Heparin-bonded endoluminal bypass for long segment lesions shows promising results (less morbidity, faster recovery, and improvement in quality of life with indistinguishable patency rates at 1 year) compared with surgical bypass. Long-term results have to be awaited.

SUrgical versus PERcutaneous Bypass: SUPERB-trial; Heparin-bonded endoluminal versus surgical femoro-popliteal bypass: study protocol for a randomized controlled trial.

BACKGROUND: Endovascular treatment options for the superficial femoral artery are evolving rapidly. For long lesions, the venous femoropopliteal bypass considered to be superior above the prosthetic bypass. An endoluminal bypass, however, may provide equal patency rates compared to the prosthetic above knee bypass. The introduction of heparin-bonded endografts may further improve patency rates. The SUrgical versus PERcutaneous Bypass (SuperB) study is designed to assess whether a heparin-bonded endoluminal bypass provides equal patency rates compared to the venous bypass and to prove that it is associated with improved quality of life, related to a decreased complication rate, or not. METHODS/DESIGN: Two-hundred-twenty-two patients with peripheral arterial occlusive disease, category 3-6 according to Rutherford, will be randomized in two treatment arms; 1. the surgical femoro-popliteal bypass, venous whenever possible, and 2. the heparin-bonded endoluminal bypass. The power analysis was based on a non-inferiority principle, with an effect size of 90% and 10% margins (alpha 5%, power 80%). Patients will be recruited from 5 teaching hospitals in the Netherlands during a 2-year period. The primary endpoint is primary patency and quality of life evaluated by the RAND-36 questionnaire and the Walking Impairment Questionnaire. Secondary endpoints include secondary patency, freedom-from-TLR and complications. DISCUSSION: The SuperB trial is a multicentre randomized controlled trial designed to show non-inferiority in patency rates of the heparin-bonded endograft compared to the surgical bypass for treatment of long SFA lesions, and to prove a better quality of life using the heparin bonded-endograft compared to surgically treatment, related to a reduction in complications. TRIAL REGISTRATION: Clinicaltrials: NCT01220245.