Treatment Strategies for Patients with Lower Extremity Chronic Venous Disease (LECVD)

Project Summary Title and Description

Title
Treatment Strategies for Patients with Lower Extremity Chronic Venous Disease (LECVD)
Description
Objectives. For patients with lower extremity chronic venous disease (LECVD), the optimal diagnostic testing and treatment for symptom relief, preservation of limb function, and improvement in quality of life is not known. This systematic review included a narrative review of diagnostic testing modalities and assessed the comparative effectiveness of exercise training, medical therapy, weight reduction, mechanical compression therapy, and invasive procedures (i.e., surgical and endovascular procedures) in patients with LECVD. Data sources. We searched PubMed®, Embase®, and the Cochrane Database of Systematic Reviews for relevant English-language studies published from January 1, 2000 to June 30, 2016. Review methods. Two investigators screened each abstract and full-text article for inclusion, abstracted the data, and performed quality ratings and evidence grading. Random-effects models were used to compute summary estimates of effects. Results. A total of 111 studies contributed evidence, as follows: Diagnosis of LECVD: A narrative review was conducted due to the scant literature and availability of only 10 observational studies evaluating the comparative effectiveness of diagnostic testing modalities in a heterogeneous population of patients with LECVD. In addition to the history and physical exam, multiple physiologic and imaging modalities (plethysmography, duplex ultrasound, intravascular ultrasonography, magnetic resonance venography, computed tomography venography, and invasive venography) are useful to confirm LECVD and/or localize the disease and guide therapy. There was insufficient evidence to support or refute the recommendations from current clinical guidelines that duplex ultrasound should be used as the firstline diagnostic test for patients being evaluated for LECVD or for those for whom invasive treatment is planned. Treatment of lower extremity chronic venous insufficiency/incompetence/reflux: Ninety-three studies (87 randomized controlled trials, 6 observational) evaluated the comparative effectiveness of exercise training, medical therapy, weight reduction, mechanical compression therapy, surgical intervention, and endovenous intervention in patients with lower extremity chronic venous insufficiency/incompetence/reflux. There was no long-term difference in effectiveness between radiofrequency ablation (RFA) and high ligation plus stripping, but RFA was associated with less periprocedural pain, faster improvement in symptom scores and quality of life, and fewer adverse events. Among patients undergoing endovenous interventions, RFA, endovenous laser ablation (EVLA), and sclerotherapy demonstrated improvement in quality-of-life scores and standardized symptom scores. When compared with patients treated with EVLA, those treated with foam sclerotherapy had significantly less periprocedural pain but lower rates of vein occlusion and higher rates of repeat intervention, and patients treated with RFA had significantly less periprocedural pain but also less short-term improvement in Venous Clinical Severity Score. When compared with patients treated with placebo, those treated with foam sclerotherapy had statistically significant improvement in standardized symptom scores, occlusion rates, and quality of life. When compared with patients treated with placebo or no compression therapy, those treated with compression therapy had significant improvement in standardized symptom scores and quality of life. Treatment of lower extremity chronic venous obstruction/thrombosis: Eight studies (3 randomized controlled trials, 5 observational) evaluated the comparative effectiveness of exercise training, medical therapy, weight reduction, mechanical compression therapy, surgical intervention, and endovenous intervention in patients with lower extremity chronic venous obstruction/thrombosis. In patients with post-thrombotic syndrome, exercise training plus patient education and monthly phone follow-up resulted in improved quality of life but not improved symptom severity when compared with patient education and monthly phone follow-up. In patients with both May-Thurner Syndrome and superficial venous reflux who were treated with EVLA (with or without stent placement), there were fewer recurrent ulcerations, improvement in reflux severity and symptoms, and improvement in quality of life in long-term follow-up. In patients with chronic proximal iliac vein obstruction, treatment with catheter-directed urokinase at the time of endovenous stenting resulted in similar effectiveness but catheter-directed urokinase had higher technical failure rates and bleeding risk when compared with endovenous stenting alone. Very few studies evaluated modifiers of effectiveness in the study population. Conclusions. The available evidence for treatment of patients with LECVD is limited by heterogeneous studies that compared multiple treatment options, measured varied outcomes, and assessed disparate outcome timepoints. Very limited comparative effectiveness data have been generated to study new and existing diagnostic testing modalities for patients with LECVD. When compared with patients’ baseline measures, endovenous interventions (e.g. EVLA, sclerotherapy, and RFA) and surgical ligation demonstrated improvement in quality-of-life scores and Venous Clinical Severity Score at various timepoints after treatment; however, there were no statistically significant differences in outcomes between treatment groups (e.g. endovenous vs. endovenous; endovenous vs. surgical). Several advances in care in endovenous interventional therapy have not yet been rigorously tested, and there are very few studies on conservative measures (e.g., lifestyle modification, compression therapy, exercise training) in the literature published since 2000. Additionally, the potential additive effects of many of these therapies are unknown. The presence of significant clinical heterogeneity of these results makes conclusions for clinical outcomes uncertain and provides an impetus for further research to improve the care of patients with LECVD.
Attribution
N/A
Authors of Report
N/A
Methodology description
We searched PubMed®, Embase®, and the Cochrane Database of Systematic Reviews for relevant English-language studies published from January 1, 2000 to June 30, 2016. Two investigators screened each abstract and full-text article for inclusion, abstracted the data, and performed quality ratings and evidence grading. Random-effects models were used to compute summary estimates of effects. See the review protocol (http://www.ahrq.gov/sites/default/files/wysiwyg/research/findings/ta/topicrefinement/lecvd_protocol.pdf) for full details.
PROSPERO
CRD42016035669
DOI
10.26300/bxpq-7s43
Notes
This project was entered retrospectively. All Data Abstraction is available in the attached file: LECVD_SRDR File_Final.xlsx .
Funding Source
The Centers for Medicare & Medicaid Services (CMS); Agency for Healthcare Research and Quality (AHRQ)

Key Questions

1. KQ 1: Narrative review of the diagnostic methods and diagnostic criteria for all adult patients (symptomatic and asymptomatic) with LE varicose veins, LE chronic venous insufficiency/incompetence/reflux, and/or LE chronic venous thrombosis/obstruction (including post-thrombotic syndrome).
2. KQ 2: Regarding treatments for all adult patients (symptomatic and asymptomatic) with LE varicose veins and/or LE chronic venous insufficiency/incompetence/reflux: [2a.] What is the comparative effectiveness of exercise, medical therapy, weight reduction, mechanical compression therapy, and invasive procedures (i.e., surgical and endovascular procedures) on health outcomes? [2b.] What diagnostic method(s) and criteria were used in each study? [2c.] How does the comparative effectiveness of treatment vary by patient characteristics, including age, sex, risk factors, comorbidities, characteristics of disease, anatomic segment affected, and characteristics of the therapy (e.g., exercise intensity, type of mechanical compression)? [2d.] What are the comparative safety concerns associated with each treatment strategy (e.g., adverse drug reactions, bleeding)? Do the safety concerns vary by patient subgroup (age, sex, race, risk factors, comorbidities, anatomic segment, or disease severity)?
3. KQ 3: Regarding treatments for all adult patients (symptomatic and asymptomatic) with LE chronic venous thrombosis/obstruction (including post-thrombotic syndrome): [3a.] What is the comparative effectiveness of exercise, medical therapy, mechanical compression therapy, and invasive procedures (i.e., surgical and endovascular procedures) on health outcomes? [3b.] What diagnostic method(s) and criteria were used in each study? [3c.] How does the comparative effectiveness of treatment vary by patient characteristics, including age, sex, risk factors, comorbidities, characteristics of disease, anatomic segment affected, and characteristics of the therapy (e.g., exercise intensity, type of mechanical compression)? [3d.] What are the comparative safety concerns associated with each treatment strategy (e.g., adverse drug reactions, bleeding)? Do the safety concerns vary by patient subgroup (age, sex, race, risk factors, comorbidities, anatomic segment, or disease severity)?

Associated Extraction Forms

Associated Studies (each link opens a new tab)

TitleAuthorsYear
A randomized trial comparing treatments for varicose veins.2014
Comparison of surgery and compression with compression alone in chronic venous ulceration (ESCHAR study): randomised controlled trial.2004
Prospective randomized study of endovenous radiofrequency obliteration (closure procedure) versus ligation and stripping in a selected patient population (EVOLVeS Study).2003
Randomized clinical trial of endovenous laser ablation compared with conventional surgery for great saphenous varicose veins.2011
Randomized clinical trial of endovenous laser ablation versus conventional surgery for small saphenous varicose veins.2013
Comparing endovenous laser ablation, foam sclerotherapy, and conventional surgery for great saphenous varicose veins.2013
Randomised clinical trial, observational study and assessment of cost-effectiveness of the treatment of varicose veins (REACTIV trial).
[Study 2] Randomised clinical trial, observational study and assessment of cost-effectiveness of the treatment of varicose veins (REACTIV trial).
[Study 3] Randomised clinical trial, observational study and assessment of cost-effectiveness of the treatment of varicose veins (REACTIV trial).2006
Comparable effectiveness of endovenous laser ablation and high ligation with stripping of the great saphenous vein: two-year results of a randomized clinical trial (RELACS study).2012
Randomized clinical trial of VNUS ClosureFAST radiofrequency ablation versus laser for varicose veins.2010
Foam-sclerotherapy, surgery, sclerotherapy, and combined treatment for varicose veins: a 10-year, prospective, randomized, controlled, trial (VEDICO trial).2003
Ultrasound-guided foam sclerotherapy combined with sapheno-femoral ligation compared to surgical treatment of varicose veins: early results of a randomised controlled trial.2006
Randomized clinical trial comparing endovenous laser with cryostripping for great saphenous varicose veins.2008
Endovenous laser ablation with and without high ligation compared with high ligation and stripping in the treatment of great saphenous varicose veins: initial results of a multicentre randomized controlled trial.2013
High ligation combined with stripping and endovenous laser ablation of the great saphenous vein: early results of a randomized controlled study.2008
A multi-centre randomised controlled trial comparing radiofrequency and mechanical occlusion chemically assisted ablation of varicose veins - Final results of the Venefit versus Clarivein for varicose veins trial.2017
Interim results on abolishing reflux alongside a randomized clinical trial on laser ablation with phlebectomies versus foam sclerotherapy.2013
Randomised controlled trial comparing sapheno-femoral ligation and stripping of the great saphenous vein with endovenous laser ablation (980 nm) using local tumescent anaesthesia: one year results.2010
Randomized clinical trial comparing endovenous laser ablation, radiofrequency ablation, foam sclerotherapy and surgical stripping for great saphenous varicose veins.2011
Randomized trial comparing endovenous laser ablation of the great saphenous vein with high ligation and stripping in patients with varicose veins: short-term results.2007
Endovenous obliteration versus conventional stripping operation in the treatment of primary varicose veins: a randomized controlled trial with comparison of the costs.2002
Conservative versus surgical treatment of venous leg ulcers: a prospective, randomized, multicenter trial.2006
Minimally invasive surgical management of primary venous ulcers vs. compression treatment: a randomized clinical trial.2003
Comparison of colour Doppler ultrasonography, ascending phlebography and clinical examination in the diagnosis of incompetent calf perforating veins.2002
Duplex ultrasonography in the diagnosis of incompetent Cockett veins.2000
Target selection for surgical intervention in severe chronic venous insufficiency: comparison of duplex scanning and phlebography.2000
Evaluation of chronic venous disease in the lower limbs: comparison of five diagnostic methods.2002
Three-Dimensional CT venography of varicose veins of the lower extremity: image quality and comparison with doppler sonography.2008
Magnetic Resonance Imaging in Proximal Venous Outflow Obstruction.2015
Diagnostic value of the femoral vein flow pattern for the detection of an iliocaval venous obstruction.2016
Validation of venous duplex ultrasound imaging in determining iliac vein stenosis after standard treatment of active chronic venous ulcers.
The value of hemodynamic measurements by air plethysmography in diagnosing venous obstruction of the lower limb.2016
Comparative study among the physical examination, echo-color Doppler mapping and operative approaching in the recurrent lower extremity varicose veins from the saphenofemoral junction.2011
The effect of stent placement for May-Thurner syndrome combined with symptomatic superficial venous reflux disease.2015
Endovenous management of venous leg ulcers. 2013
Endovascular management of iliac vein compression (May-Thurner) syndrome.2000
Prevention and treatment of postphlebitic syndrome: results of a 3-part study.2001
Six-month exercise training program to treat post-thrombotic syndrome: a randomized controlled two-centre trial.2011
Factors affecting outcome of open and hybrid reconstructions for nonmalignant obstruction of iliofemoral veins and inferior vena cava.2011
Efficacy of a short course of complex lymphedema therapy or graduated compression stocking therapy in the treatment of post-thrombotic syndrome.2014
Clinical Assessment of Endovascular Stenting Compared with Compression Therapy Alone in Post-thrombotic Patients with Iliofemoral Obstruction.2015
Sclerotherapy of telangiectases and reticular veins: a double-blind, randomized, comparative clinical trial of polidocanol, sodium tetradecyl sulphate and isotonic saline (EASI study).2010
A prospective double-blind randomized controlled trial of radiofrequency versus laser treatment of the great saphenous vein in patients with varicose veins.2011
Laser and radiofrequency ablation study (LARA study): a randomised study comparing radiofrequency ablation and endovenous laser ablation (810 nm).2010
Randomized clinical trial of endovenous laser ablation versus steam ablation (LAST trial) for great saphenous varicose veins.2014
Radiofrequency endovenous ClosureFAST versus laser ablation for the treatment of great saphenous reflux: a multicenter, single-blinded, randomized study (RECOVERY study).2009
Randomised, double blind, multicentre, placebo controlled study of sulodexide in the treatment of venous leg ulcers.2002
Treatment of Truncal Incompetence and Varicose Veins with a Single Administration of a New Polidocanol Endovenous Microfoam Preparation Improves Symptoms and Appearance.2015
The VANISH-2 study: a randomized, blinded, multicenter study to evaluate the efficacy and safety of polidocanol endovenous microfoam 0.5% and 1.0% compared with placebo for the treatment of saphenofemoral junction incompetence.2014
A multicenter, randomized, placebo-controlled study to evaluate the efficacy and safety of Varithena® (polidocanol endovenous microfoam 1%) for symptomatic, visible varicose veins with saphenofemoral junction incompetence.2017
A multicenter, randomized, placebo-controlled trial of endovenous thermal ablation with or without polidocanol endovenous microfoam treatment in patients with great saphenous vein incompetence and visible varicosities.2017
Randomized trial comparing cyanoacrylate embolization and radiofrequency ablation for incompetent great saphenous veins (VeClose).2015
Reverse foam sclerotherapy of the great saphenous vein with sapheno-femoral ligation compared to standard and invagination stripping: a prospective clinical series.2008
Effect of a mixed kinesio taping-compression technique on quality of life and clinical and gait parameters in postmenopausal women with chronic venous insufficiency: double-blinded, randomized controlled trial.2014
A randomized controlled trial of a mixed Kinesio taping-compression technique on venous symptoms, pain, peripheral venous flow, clinical severity and overall health status in postmenopausal women with chronic venous insufficiency.2014
Effects of kinesio taping on venous symptoms, bioelectrical activity of the gastrocnemius muscle, range of ankle motion, and quality of life in postmenopausal women with chronic venous insufficiency: a randomized controlled trial.2013
Chronic Venous Insufficiency: prevalence and effect of compression stockings.2014
Endovascular sclerotherapy, surgery, and surgery plus sclerotherapy in superficial venous incompetence: a randomized, 10-year follow-up trial--final results.2000
Superficial venous incompetence: low-cost outpatient minisurgery, sclerotherapy and combined procedure as a management plan. Costs and efficacy. A 20-year, follow-up registry.2016
A prospective randomized study comparing polidocanol foam sclerotherapy with surgical treatment of patients with primary chronic venous insufficiency and ulcer.2015
A multicenter randomized controlled trial evaluating balneotherapy in patients with advanced chronic venous insufficiency.2014
Randomized clinical trial of concomitant or sequential phlebectomy after endovenous laser therapy for varicose veins.2009
Interventions on the superficial venous system for chronic venous insufficiency by surgeons in the modern era: an analysis of ACS-NSQIP.2014
Prospective randomized trial comparing endovenous laser ablation and surgery for treatment of primary great saphenous varicose veins with a 2-year follow-up.2010
Health-related quality of life during four-layer compression bandaging for venous ulcer disease: a randomised controlled trial.2005
Randomized clinical trial comparing endovenous laser ablation with surgery for the treatment of primary great saphenous varicose veins.2008
Ambulatory phlebectomy versus compression sclerotherapy: results of a randomized controlled trial.2003
Influence of aspirin therapy in the ulcer associated with chronic venous insufficiency.2012
Results of surgical treatment compared with ultrasound-guided foam sclerotherapy in patients with varicose veins: a prospective randomised study.2009
A randomized, controlled trial of endovenous thermal ablation using the 810-nm wavelength laser and the ClosurePLUS radiofrequency ablation methods for superficial venous insufficiency of the great saphenous vein.2010
Foam sclerotherapy of the saphenous veins: randomised controlled trial with or without compression.
Great saphenous vein radiofrequency ablation versus standard stripping in the management of primary varicose veins-a randomized clinical trial.2011
To wear or not to wear compression stockings after varicose vein stripping: a randomised controlled trial.2009
The prepare pilot RCT of home-based progressive resistance exercises for venous leg ulcers.2009
Efficacy of sclerotherapy in varicose veins-- prospective, blinded, placebo-controlled study.2004
A randomized trial of cryo stripping versus conventional stripping of the great saphenous vein.2009
Intermittent pneumatic compression as an adjuvant therapy in venous ulcer disease.2002
Intravenous catheter-guided laser ablation: a novel alternative for branch varicose veins.2011
Ultrasound-guided foam sclerotherapy of the great saphenous vein with sapheno-femoral ligation compared to standard stripping: a prospective clinical study.2011
Conventional stripping versus cryostripping: a prospective randomised trial to compare improvement in quality of life and complications.2008
1064 nm Nd:YAG long pulse laser after polidocanol microfoam injection dramatically improves the result of leg vein treatment: a randomized controlled trial on 517 legs with a three-year follow-up.2014
Endovenous laser ablation of the great saphenous vein versus high ligation: long-term results.2014
A factorial, randomized trial of pentoxifylline or placebo, four-layer or single-layer compression, and knitted viscose or hydrocolloid dressings for venous ulcers.2007
Pentoxifylline--efficient in the treatment of venous ulcers in the absence of compression?2002
Outcomes associated with ablation compared to combined ablation and transilluminated powered phlebectomy in the treatment of venous varicosities.2016
Randomised clinical trial of foam sclerotherapy for patients with a venous leg ulcer.2010
Varicose vein surgery: stripping versus the CHIVA method: a randomized controlled trial.2010
A comparison between cryosurgery and conventional stripping in varicose vein surgery: perioperative features and complications.2006
Compression therapy versus surgery in the treatment of patients with varicose veins: A RCT.2014
Low molecular weight heparin improves healing of chronic venous ulcers especially in the elderly.2015
Randomized clinical trial of ultrasound-guided foam sclerotherapy versus surgery for the incompetent great saphenous vein.2012
Randomized clinical trial of radiofrequency ablation or conventional high ligation and stripping for great saphenous varicose veins.2010
Endovenous laser ablation: does standard above-knee great saphenous vein ablation provide optimum results in patients with both above- and below-knee reflux? A randomized controlled trial.2008
Randomized clinical trial of endovenous microwave ablation combined with high ligation versus conventional surgery for varicose veins.2013
Assessment of the efficacy and safety of steam vein sclerosis as compared to classic surgery in lower extremity varicose vein management.2015
Randomized controlled trial comparing treatment outcome of two compression bandaging systems and standard care without compression in patients with venous leg ulcers.2012
Endovenous laser treatment for varicose veins in patients with active ulcers: measurement of intravenous and perivenous temperatures during the procedure.2007
The efficacy and safety of a coumarin-/troxerutin-combination (SB-LOT) in patients with chronic venous insufficiency: a double blind placebo-controlled randomised study.2002
Endovenous laser ablation (EVLA) versus high ligation and striping (HL/S): Two-years follow up.2011
Analysis of venous thromboembolic events after saphenous ablation.2013
Role of compression stockings after endovenous laser therapy for primary varicosis.2014
Perioperative quality assessment of varicose vein surgery : Commission for quality assessment of the German Society for Vascular Surgery.2016
Endovenous laser ablation versus conventional surgery in the treatment of small saphenous vein incompetence.2013
Hemodynamic surgery versus conventional surgery in chronic venous disease: A multicenter retrospective study.2013
Efficacy of high voltage stimulation for healing of venous leg ulcers in surgically and conservatively treated patients.2006
Randomized clinical trial of varicose vein surgery with compression versus compression alone for the treatment of venous ulceration.2003
Comparative outcomes of radiofrequency endoluminal ablation, invagination stripping, and cryostripping in the treatment of great saphenous vein insufficiency2006
Graduated compression elastic stockings reduce lipodermatosclerosis and ulcer recurrence2000
Varisolve® polidocanol microfoam compared with surgery or sclerotherapy in the management of varicose veins in the presence of trunk vein incompetence: European randomized controlled trial2006
Hemodynamic classification and CHIVA treatment of varicose veins in lower extremities (VVLE).2016

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