Systemic enzyme therapy in chronic venous disease: a review

Chronic venous disease (CVD), a sequel of venous insufficiency, has great medical and socioeconomic impact. Varicose veins and venous ulcer are amongst its commonest manifestations. In CVD, incompetent valves, weakened vascular walls, venous hypertension and increased permeability of venous walls lead to the release of proinflammatory mediators like tumor necrosis factor (TNF)-α, interleukin (IL)-1β, reactive oxygen species (R.O.S.), and reactive nitrogen species (R.N.S.) in the venous milieu. Pharmacotherapy with nonsteroidal anti-inflammatory drugs (NSAIDs) is often used to relieve pain caused by venous disease. However, there is a need for therapies that target the microcirculatory disorders and act on chronic inflammatory processes. Systemic enzyme therapy (SET), with orally administered combination of proteolytic enzymes- trypsin, bromelain, and flavonoid rutoside, has been used since decades for their anti-inflammatory, analgesic, anti-edematous, antithrombotic and antioxidant properties. This review discusses the various relevant pharmacodynamic properties demonstrated by the ingredients, followed by clinical studies of SET, which have demonstrated benefit in both subjective and objective parameters. These studies indicate that SET has good efficacy, tolerability and holds great promise to improve the quality of life of a patient with CVD.