A Prospective Study of the Long-Term Efficacy of Two Different Venoactive Drugs in Patients with Post-Thrombotic Syndrome

Abstract

Objective: In an open cross-over study, the effect of two different venoactive drugs was prospectively studied in a series of patients with post-thrombotic syndrome. Design: Prospective, open cross-over study. Patients: Twenty-nine patients with established unilateral deep venous insufficiency of at least 12 months duration, and a history of venography-proven deep venous thrombosis in the affected leg. Interventions: On entering the study, patients were randomly assigned to receive either Hidrosmina (Venosmil, FAES SA, Spain) 600 mg daily, or 0-(β-hydroxyethyl)-rutosides (Venoruton, Zyma SA, Switzerland) 900 mg daily. The drugs were taken for 6 months. At the end of this period, the drug was discontinued, and patients taking Hidrosmina changed to rutosides, or vice versa, for a further 6-month period. Finally, both drugs were discontinued, and patients were re-examined 3 and 6 months later. Results: During the first 6-month period, 12 out of 29 patients showed reduced tiredness and/or pain in the leg in comparison to the control visit. Furthermore, a slight reduction was found in mean circumferences of both the ankle and calf during this study period. During the second 6-month period of therapy, six additional patients improved their subjective symptoms, but there were three patients in whom these symptoms had increased. Six months after discontinuation of therapy, subjective symptoms increased in 10 out of 29 patients, and mean circumferences of both the ankle and calf returned to baseline values. Conclusions: In this pilot study our findings demonstrate that venoactive drugs may improve both objective and subjective symptoms in patients with post-thrombotic syndrome, and that these effects disappear after drug therapy is discontinued.

The Postthrombotic Syndrome: Evidence-Based Prevention, Diagnosis, and Treatment Strategies

“…113 The drugs evaluated were rutosides (thought to reduce capillary filtration rate and microvascular permeability to proteins), defibrotide (downregulates plasminogen activator inhibitor-I release and upregulates prostacyclin, prostaglandin E2, and thrombomodulin), by guest on http://circ.ahajournals.org/ Downloaded from October 28, 2014 and hidrosmin (unknown mechanism of action). 114 The main features of these studies are shown in Table 9.…”

“…Monreal et al 113 showed that both hidrosmin and rutosides reduced symptoms but that hidrosmin produced greater improvement. Statistically significant improvement in pain and edema scores was observed by Coccheri et al 112 with defibrotide versus placebo, whereas claudication, skin pigmentation, and lipodermatosclerosis were unchanged.…”

“…Finally, a similar proportion of patients treated with compression stockings alone, rutosides alone, and a combination of compression stockings and rutosides showed symptom improvement (70%, 65%, and 63%, respectively) or deterioration (15%, 23%, and 23%) in the study by Frulla et al 49 Notably, in the only study in which follow-up continued for 6 additional months after treatment completion, the drug effect virtually disappeared. 113 Three of 4 studies reported on side effects, which were mostly mild and balanced between groups. 49,111,112 In the de Jongste et al 111 study, 7 of 41 patients (17%) in the rutosides group and 4 of 42 (12%) in the placebo group reported headache, hair loss, swollen fingers, muscle stiffness, rash, or dizziness.…”

Prevention and Management of the Post-Thrombotic Syndrome

“…Venoactive drugs' mechanism of action is not entirely clear [96]. Rutosides are thought to reduce capillary permeability [97,98]; defibrotides downregulate plasminogen activator inhibitor-1 and upregulate prostaglandin, prostacyclin and thrombomodulin [99]; and flavonoids have a multi-faceted mechanism of action [100]. The micronized purified flavonoid fraction (MPFF) contains a combination of several flavonoids, and is thought to increase venous tone, reduce stasis, reduce venous wall inflammation and increase capillary permeability [101].…”

Anti-oedematous Effect of Hidrosmin on Thermal Injury Oedema and Acute Lymphoedema in the Rat Hind Leg

“…It has been shown that hidrosmin reduces the increase of vascular permeability induced by bradikinin, histamine and other mediators, and that it has a vitamin P-like activity (Quintana et al 1988). Moreover, hidrosmin increased human red blood cell deformability in-vitro (Iriarte et al 1988a) and ex-vivo (Iriarte et al 1988b), is used in the clinical management of chronic venous insuf®ciency (Boada et al 1992;Monreal et al 1994), and is effective in the prevention of the development of clinical symptoms of venous insuf®ciency after venous thrombosis (Monreal et al 1997).…”