Chronic Venous Disease: Varicose Veins And Venous Insufficiency
Novel And Emerging Strategies
CHIVA (Conservative Hemodynamic Cure for Venous Insufficiency)
CHIVA, a French acronym for “conservative hemodynamic cure for venous insufficiency,” is an office-based, minimally invasive, well-studied procedure for treating varicose veins that result from chronic venous insufficiency. CHIVA is more readily available in Europe than in the United States or elsewhere. CHIVA is unique among venous disease treatments in that it preserves rather than destroys superficial veins, attempting to restore healthy blood flow by correcting venous hypertension (Bellmunt-Montoya 2015; Mowatt-Larssen 2010; Gohel 2014; Franceschi 2016).
CHIVA accomplishes this with detailed duplex ultrasound scanning and pre-operative mapping of blood flow in the venous system. Then, precisely placed vein ligations (tying off) redirect blood flow into deeper veins, bypassing the superficial veins, and minimizing reflux. Another unique aspect of CHIVA is that rather than attempting to completely eliminate all reflux, as in other surgical methods, CHIVA’s goal is interruption of venous hypertension at its source, higher up in the venous system (Mowatt-Larssen 2010; Franceschi 2016).
Multiple studies have found the CHIVA method results in a low rate of recurrence, including when compared with surgical vein stripping and endovenous laser ablation, with comparable or superior clinical and cosmetic improvement. Compared with vein stripping, CHIVA is associated with fewer adverse effects including bruising and nerve injuries, less damage, and rapid recovery (Bellmunt-Montoya 2015; Zmudzinski 2017; Wang 2016).
Skin substitutes made of synthetic or naturally-derived materials can help the healing of chronic wounds including venous ulcers. Skin substitutes provide a structural framework and biological factors that promote healing. They can be used as a complement to traditional wound care (Nathoo 2014).
Dermagraft is a skin substitute created from human fibroblast cells that are grown on a bioactive mesh scaffold material. Dermagraft is FDA approved for the treatment of diabetic foot ulcers, and has been studied for the treatment of venous leg ulcers (Hart 2012).
Dermagraft improved healing of venous ulcers when combined with compression therapy (Harding 2013; Omar 2004). In a multicenter, randomized, controlled trial in patients with venous leg ulcers, among those with ulcers of less than 12 months duration, significantly more of those treated with Dermagraft plus compression therapy were healed by week 12 than control participants treated with compression therapy alone (Harding 2013).
Dermagraft is fairly safe, though complications such as skin and bone infections have been reported (Nathoo 2014).
Apligraf is a bilayer skin substitute that blends viable human fibroblasts and skin cells with bovine collagen. It is FDA approved for venous ulcers of greater than one month duration that have not adequately responded to standard therapy, as well as diabetic foot ulcers of greater than one-month duration (Nicholas 2016; Nathoo 2014).
Treatment with Apligraf plus compression therapy has been shown to be superior to compression alone, particularly in the healing of larger and deeper ulcers. Apligraf is also more effective for ulcers present for more than six months duration (Nicholas 2016; Zaulyanov 2007; Falanga 1998).
EpiFix is a skin substitute composed of dehydrated human membranes along with their epithelial cells, which exhibit stem cell-like features (Nicholas 2016; Serena 2014). In a randomized controlled clinical trial, leg ulcers treated with EpiFix in addition to multilayer compression therapy had an average reduction in size over four weeks of 48.1% compared with 19% for those treated with compression only (Serena 2014).
EpiFix’s ability to recruit stem cells to the ulcer site is one potential mechanism for its clinical effect. These adult stem cells play an important role in the maintenance and repair of wounded tissue (Massee 2016).
“Spray-On Skin” Cell Therapy
A spray-applied cell therapy consisting of a mixture of human skin cells and proteins may help heal chronic venous leg ulcers without the use of skin grafts (Kirsner 2012).
In a randomized controlled trial, researchers applied one of two different strength formulations of human keratinocytes and fibroblasts derived from human skin to patients’ venous ulcers every 7 or 14 days for 12 weeks. Patients in the treatment groups had a significantly greater average reduction in wound area compared with patients in the placebo group. Adverse effects were similar between the groups (Kirsner 2012). In a 24-week follow-up study, the authors concluded that the benefit of this treatment persisted for several weeks beyond the last application (Kirsner 2013).
Sulodexide is a highly purified complex of glycosaminoglycans (naturally occurr ulcers. Sulodexide reduces the formation of blood clots and has anti-inflammatory properties (Wu 2016; Eberhardt 2014; Coccheri 2014).
Clinical studies have shown that sulodexide promotes healing of venous ulcers, improves symptoms, and is safe and well tolerated when used alongside local wound care (Wu 2016; Andreozzi 2012). Other evidence suggests sulodexide may reduce the risk of blood clot recurrence in people with a history of venous thromboembolism (Shaydakov 2016; Andreozzi 2015).
Although available in some countries in Europe, South America, and Asia, sulodexide is not approved for use in the United States (Pullen 2011).
Oxerutin. Oxerutin (hydroxyethylrutosides) is a standardized mixture of semisynthetic flavonoids derived from rutin, a naturally occurring flavonoid (Aziz 2015; Firuzi 2011).
Oxerutin is commonly used in Europe in the treatment of venous disorders. Multiple clinical trials have demonstrated that oxerutin reduces edema and pain associated with venous disease (Wadworth 1992; Petruzzellis 2002; Eberhardt 2014).
These benefits of oxerutin have been attributed to an ability to reduce excessive permeability (leakage of fluid) of veins, which can result in edema, and to an improvement in venous blood circulation (Rabe 2013; Yildiz 2016).