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.