Implications for Pharmacological Treatment in Venous Disease

Although bandaging and stockings have been used effectively in the treatment of chronic venous insufficiency for many years, modern pharmacological science may provide assistance in healing venous ulcers and perhaps some insight into the mechanisms of the disease.

Pentoxifylline has been used for the treatment of claudication for a number of years, with moderate success. Its mechanism of action is probably through an effect on inhibition of cytokine-mediated neutrophil activation.45 Its efficacy in healing venous leg ulcers has been reported in a recent meta-analysis.46 Nine trials involving 572 adults were included. Pentoxifylline plus compression is more effective than placebo plus compression (relative risk of healing with pentoxifylline 1.30, 95% confidence interval 1.10-1.54).

This drug could be considered for use in patients with venous leg ulceration when used in combination with compression.

Prostaglandin Ej (PGEj) has a number of profound effects on the microcirculation, including reduction of white cell activation, platelet aggregation inhibition, small vessel vasodilatation, and reduction of vessel wall cholesterol levels. Recently the results of a randomized, placebo-controlled, single blind study in which 87 patients who had venous leg ulcers has been reported.47 Patients were treated with compression bandaging and conventional wound management. They also received treatment for 20 days with an infusion of prostaglandin Ej analogue (Prostavasin, Schwarz Pharma) or placebo. After four months, all ulcers were healed in the active treatment group but only 32 of 38 in the placebo group. This is a potentially useful drug but the limitation of giving intravenous infusions restricts it applicability.

Laurent et al. investigated micronized purified flavonoid fraction (MPFF)48 and showed that this drug reduced the symptoms of venous disease (aching, itching, feeling of swelling) and also reduced ankle edema. More recently MPFF has been studied for its effects on venous leg ulcer healing. A meta-analysis has been published in which five prospective, randomized, controlled studies involving 723 patients with venous ulcers were included.49 Patients were treated with compression bandaging and local wound care in all cases. In two studies MPFF was compared to placebo and in three studies MPFF was compared to standard treatment alone. At six months, the chance of healing ulcer was 32% better in patients treated with adjunctive MPFF than in those managed by conventional therapy alone. The main benefit of MPFF was present in the subgroup of ulcers between 5 and 10 cm2 in area and those present for six to 12 months duration. MPFF therefore may be a useful drug to combine with compression management in countries where it is licensed.

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