Chronic venous insufficiency - Emerging treatments

Balneotherapy

Balneotherapy is a traditional medical technique using water. One Cochrane review has assessed the use of balneotherapy in the management of patients with CVI and found that compared with no treatment, there is probably no improvement in disease severity signs and symptoms, but there are improvements in health‐related quality of life and pain and reductions in skin pigmentation changes.[36]

Biologicals (amnion/chorion allografts)

Amniotic membrane contains wound-healing proteins and growth factors and it has been studied in treatment of chronic venous leg ulcers. In one randomised controlled trial, 101 patients with chronic venous leg ulcers were randomised to receive either dehydrated human amnion and chorion allograft with standard of care or standard of care alone. Addition of dehydrated human amnion and chorion allograft to standard of care resulted in more healed ulcers at 12 weeks (75% compared with 30%).[37]

Spray-applied cell therapy

Results from one phase 2 double-blind randomised controlled trial of 205 people with venous leg ulcers suggest that dosing of growth-arrested allogeneic neonatal keratinocytes and fibroblasts in a fibrin vehicle is associated with a higher proportion of healing when compared with vehicle alone.[38] These promising results warrant further studies in this area.

Other pharmacological therapies

A number of initial trials support some benefit to patients with CVI from a number of agents, including venoactive drugs (VADs), calcium dobesilate, and red-vine-leaf extract.[39][40][41] Pain, oedema, and leg volume appear to be reduced, but further trials with better stratification of disease type and severity are needed before the use of these agents can be recommended.

Exercise

A systematic review and meta-analysis of five randomised clinical trials comprising 190 patients with venous leg ulcers has shown that exercise may be an effective adjuvant to compression for the treatment of venous leg ulcers.[42] The exercise interventions were progressive resistance exercise alone or combined with prescribed physical activity, walking only, or ankle exercises. Progressive resistance exercise combined with prescribed physical activity appeared to be most effective, although the effect was reported to be imprecise (additional 27 cases healed in 100 patients; 95% CI 9 to 45 cases in 100; P=0.004).[42] On the whole, exercise was associated with increased venous ulcer healing at 12 weeks, although the effect was reported to be imprecise (additional 14 patients healed per 100; 95% CI 1 to 27 cases in 100; P=0.04). European Society of Vascular Surgery guidelines note that there is a lack of studies on exercise in CVI, but suggest that the indirect evidence for the benefit on venous function is considerable and that it should therefore be promoted.[2] One Cochrane review found that there is currently insufficient evidence to assess the benefits and harms of physical exercise programmes for the treatment of individuals with non‐ulcerated CVI.[43]