Are the phlebotonic properties shown in clinical pharmacology predictive of a therapeutic benefit in chronic venous insufficiency? Our experience with Daflon 500 mg. Hydroxyethylrutosides in elderly patients with chronic venous insufficiency: its efficacy and tolerability. PYCNOGENOL in chronic venous insufficiency. Doxium 500 in chronic venous insufficiency: a double-blind placebo controlled multicentre study. Investigation of the efficacy of oxerutins compared to placebo in patients with chronic venous insufficiency treated with compression stockings. Leg oedema protection from a buckwheat herb tea in patients with chronic venous insufficiency: a single-centre, randomised, double-blind, placebo-controlled clinical trial. The efficacy and safety of a coumarin-/troxerutin-combination (SB-LOT) in patients with chronic venous insufficiency: a double blind placebo-controlled randomised study. A portable pulsed electromagnetic field (PEMF) device to enhance healing of recalcitrant venous ulcers: a double-blind, placebo-controlled clinical trial. Pycnogenol in chronic venous insufficiency. Comparison of leg compression stocking and oral horse-chestnut seed extract therapy in patients with chronic venous insufficiency. High versus low doses of unfractionated heparin for the treatment of superficial thrombophlebitis of the leg. A prospective, controlled, randomized study. Medical edema protection--clinical benefit in patients with chronic deep vein incompetence. A placebo controlled double blind study. Topical treatment of venous microangiopathy in patients with venous ulceration with Essaven gel--a placebo-controlled, randomized study. The effect of hydroxyethylrutosides on capillary filtration in moderate venous hypertension: a double blind study. Comparative clinical efficacy and tolerability of oxerutins and horse chestnut extract in patients with chronic venous insufficiency. Anticoagulant therapy in deep venous thrombosis. A randomized controlled study. Intermittent sequential pneumatic compression of the legs and thromboembolism-deterrent stockings in the prevention of postoperative deep venous thrombosis. Superficial thrombophlebitis of the legs: a randomized, controlled, follow-up study. Improvement of microcirculation and healing of venous hypertension and ulcers with Crystacide. Evaluation of free radicals, laser Doppler flux and PO2. A prospective-randomized-controlled study. The efficacy of pneumatic compression stockings in the prevention of pulmonary embolism after cardiac surgery. Prevention and treatment of postphlebitic syndrome: results of a 3-part study. Efficacy of a 6-month treatment with Daflon 500 mg in patients with venous leg ulcers associated with chronic venous insufficiency. Controlled, randomized clinical trial of 2 hydrocolloid dressings in the management of venous insufficiency ulcers. Improvement of microcirculation and healing of venous hypertension and ulcers with Crystacide: evaluation with a microcirculatory model, including free radicals, laser doppler flux, and PO2/PCO2 measurements.
In 3 controlled clinical trials, double blind versus placebo, the activity of Daflon 500 mg, a new micronised flavonoid fraction, has been evaluated on venous tone using venous plethysmography. A double-blind, randomized cross-over Phase II pharmaco-clinical trial has shown that Daflon 500 mg is statistically more effective than placebo on pathological legs, as well as normal legs. In this study, which included 20 patients suffering from post-thrombotic syndrome, Daflon 500 mg decreased: 1) venous capacity (p less than 0.001); 2) venous distensibility (p less than 0.001); 3) venous outflow time, measured by the two parameters total emptying venous time (p less than 0.001) and T2p (p less than 0.001). These modifications have been observed 2 hours after administration without any significant change in T50 outflow, cardiad index, capillary filtration index, blood pressure, cardiac or respiratory rate. The same acute effect of increasing venous tone has been demonstrated in another pharmacoclinical trial, 1 and 2 hours after ingestion in 3 groups of 10 women suffering from venous insufficiency: group I without varicose, group II during pregnancy and group III with a post-thrombotic syndrome. Finally, in a Phase III clinical trial, in 2 parallel groups of 20 patients each with functional chronic venous insufficiency, Daflon 500 mg has been compared to placebo. It was then demonstrated after 1 and 2 months treatment an improvement in the functional symptoms and edema accompanied by a statistically significant increase of the venous tone. (ABSTRACT TRUNCATED AT 250 WORDS) The efficacy and tolerability of O-(beta-hydroxyethyl)-rutosides (HR) in elderly patients (aged over 65 years) with chronic venous insufficiency or varicose veins was studied in a multicentre, double-blind, randomised, placebo-controlled trial. Of the 104 patients entered into the trial, data from 102 were available for analysis of tolerability and from 86 for efficacy. Treatment was for 6 months, with monthly examinations. Three different dosages were used due to slight differences in the registered dosage in various countries: (1) 250 mg 4 times daily (1 g/day), UK, n = 19 patients; (2) 300 mg 3 times daily (900 mg/day), FRG and Belgium, n = 55, and (3) 300 mg 4 times daily (1,200 mg/day), The Netherlands, n = 30. Each centre had its own placebo control group. The HR-treated group (n = 41) showed a significantly greater reduction in the total symptom score, 5.7 +/- 2.4 to 2.3 +/- 1.8, than in the placebo group, 4.4 +/- 3.0 to 3.0 +/- 2.4 (p < 0.01). Of the 5 studied symptoms there was also a significant (p < 0.05) improvement in leg cramps, heavy legs and restless legs. No significant differences between the two groups were seen for aching pains and paraesthesia. A small reduction was also seen in ankle and calf circumferences, which became significant at the end of the trial (p < 0.05). Pitting oedema of the leg (p < 0.01) and eczema of the leg (p < 0.05) also improved significantly greater than in the control group.(ABSTRACT TRUNCATED AT 250 WORDS) The aim of out study was to investigate the efficacy of Pycnogenol - a French maritime pine bark extract - in the treatment of chronic venous insufficiency (CVI). The study consisted of a double-blind phase - in which 20 patients were recruited and randomly treated with placebo or Pycnogenol (100 mg 2 3/day for 2 months) - and an open phase - in which other 20 patients were treated with Pycnogenol at the same dose schedule. In total, 40 patients were enrolled; 30 of them were treated with Pycnogenol and 10 with placebo. Pycnogenol significantly improved the legs' heaviness and subcutaneous edema; the venous pressure was also significantly reduced by the Pycnogenol treatment, thus adding further clinical evidence to its therapeutic efficacy in patients with CVI. Pycnogenol was effective, probably by either stabilizing the collagenous subendothelial basal membrane or scavenging the free radicals, or by a combination of these activities. Clinically, capillary leakage, perivascular inflammation and subcutaneous edema were all reduced. The safety of use of Pycnogenol is demonstrated by the lack of side effects or changes in blood biochemistry and hematologic parameters. Pycnogenol can be therefore recommended both for prevention and treatment of CVI and related veno-capillary disturbances. The aim of this double-blind placebo-controlled study was to evaluate the therapeutic efficacy of Doxium in chronic venous insufficiency (CVI). 225 patients were treated randomly for 4 weeks with 1.5 g (3 capsules/day) of Doxium or placebo. The evolution of the leg oedema was determined by measuring calf and ankle circumferences. Pain and discomfort were assessed by visual analogue scale. The results show that at the end of the trial, all the examined parameters (leg oedema, pain, day and night cramps, discomfort, heavy legs, paresthesia and restless legs) were significantly more improved in the Doxium group than in the placebo group: the leg volume was diminished by 3.8% in the Doxium group compared to 1.2% in the placebo (p less than 0.005). The overall assessment by the physicians showed an improvement in 82% of the Doxium-treated patients compared to 42% of the placebo group (p less than 0.0001). The tolerance of the treatment was comparable in both groups. The aim of this study was to investigate, if the the combined treatment of compression stockings and drug treatment with oxerutins (O-(beta-hydroxyethyl)-rutosides, Venoruton) provides additional benefit for patients with chronic venous insufficiency (CVI) compared to compression treatment alone. Oxerutins belong to the group of oedema protective agents and possess anti-exudative and membrane protective activity. A total of 133 female patients with CVI grade II participated in this double-blind, randomised, multi-centre, parallel-group study with two treatment groups. The whole study lasted for 19 weeks, and consisted of a one week placebo run-in phase, 12 weeks treatment phase, followed by a 6 weeks treatment-free follow-up period. All patients received a basis compression therapy that consisted of standard compression stockings. In order to standardise initial fitting of stockings in this multi-centre setting, stockings were fitted after one week of standard diuretics starting at baseline and then stockings were worn for the following 11 weeks. Patients were randomised to receive oxerutins (2 x 500 mg daily) or matching placebo. Leg volumes (water displacement) and associated subjective symptoms (visula analogue scale) were measured during a placebo run-in period at enrolment (week - 1) and half a week later (week - 1/2), at baseline week 0), at 4, 8, 12 weeks on treatment, and again after a 3- and 6-weeks treatment-free follow-up. The primary efficacy criterion, the area under the baseline from week 0 to week 18 (AUB0-18) of leg volume changes, as measurement of the global change of leg oedema during the study, resulted in a superior reduction of -5589 ml.d for the combined treatment with oxerutins compared to -2101 ml.d for placebo (p = 0.012). The mean change of leg volume compared to baseline after 12 weeks of treatment was -63.9 ml for stockings and oxerutins, and -32.9 ml for the patients who received stockings and placebo (p < 0.05). Oxerutins showed a prolonged effect in the follow-up phase compared to placebo, with mean AUB values for week 12 to week 18 of -1769 ml.d versus -133 ml.d (p < 0.01). The study demonstrated that the combined therapy of compression stockings and drug treatment with oxerutins is significantly superior in reducing leg oedema resulting from chronic venous insufficiency compared to compression treatment alone. The efficacy of a buckwheat herb tea was determined in patients with chronic venous insufficiency (CVI) in a single-centre, randomised, double-blind, placebo-controlled clinical trial.
                Sixty-seven male and female patients (22-74 years) with CVI were randomly divided into two groups after a 2-week run-in period. They received either buckwheat herb tea (Fagopyrum esculentum) or a placebo tea for a period of 3 months. The main outcome measure was the lower leg volume determined by ultrasound. Subjective symptoms were assessed by a clinical symptom score system. The femoral vein diameters were measured by B-scan sonography. In a subgroup of patients capillary permeability was determined by cutaneous fluorescence angiography.
                Although the mean partial leg volume did not change in the treatment group (from 2041 to 2073 ml), it increased in the placebo group by 110 ml (from 1972 to 2082 ml) according to intent to treat. The difference between the groups was significant. The subjective clinical symptoms were significantly reduced in both groups. The mean diameters of the femoral veins were reduced and capillary permeability was improved, but neither change was statistically significant. No drug-related adverse effects were observed.
                CVI is a very placebo-sensitive condition. The treatment with buckwheat herb tea is safe and could have a favourable influence on patients with CVI such that further oedema development is prevented. The objective was to evaluate the oedema-protective effect of a vasoactive drug (coumarin/troxerutin [SB-LOT]) plus compression stockings in patients suffering from chronic venous insufficiency after decongestion of the legs as recommended by the new guidelines.
                231 patients were randomly assigned medical compression stockings plus SB-LOT (90 mg coumarin and 540 mg troxerutin per day) or medical compression stockings plus placebo for the first 4 weeks and SB-LOT or placebo for the second 12 weeks of the study. The primary efficacy endpoint was the lower leg volume measured by well-established water plethysmometry.
                226 patients were evaluated. After ceasing compression stockings, an edema protective effect was detected in the SB-LOT-group but not in the controls. Recurrence of leg volume increase was by 6.5 +/- 12.1 ml and by 36.7 +/- 12.1 ml in the SB-LOT and placebo group, respectively (p = 0.0402). The local complaint score and general aspects of quality of life were also superior for the SB-LOT-group (p = 0.0041). Significant differences were also observed with regard to clinical global impression and therapeutic effect. No serious adverse drug reaction or clinically relevant impairment of laboratory parameters occur.
                This study confirms the oedema-protective effect of SB-LOT in chronic venous insufficiency and provides a treatment option for patients who discontinue compression after a short time. A prospective, randomized, double-blind, placebo-controlled multicentre study assessed the clinical efficacy and safety of pulsed electromagnetic limb ulcer therapy (PELUT) in the healing of recalcitrant, predominantly venous leg ulcers. The portable device was used at home for 3 h daily during this 8-week clinical trial as an adjunct to a wound dressing. Wound surface area, ulcer depth and pain intensity were assessed at weeks 0, 4 and 8. At week 8 the active group had a 47.7% decrease in wound surface area vs. a 42.3% increase for placebo (P < 0.0002). Investigators' global evaluations indicated that 50% of the ulcers in the active group healed or markedly improved vs. 0% in the placebo group, and 0% of the active group worsened vs. 54% of the placebo group (P < 0.001). Significant decreases in wound depth (P < 0.04) and pain intensity (P < 0.04) favouring the active group were seen. Patients whose ulcers improved significantly after 8 weeks were permitted to continue double-blind therapy for an additional 4 weeks. Eleven active and one placebo patient continued therapy until week 12, with the active treatment group continuing to show improvement. There were no reports of adverse events attributable to this device. We conclude that the PELUT device is a safe and effective adjunct to non-surgical therapy for recalcitrant venous leg ulcers. Forty patients with chronic venous insufficiency (CVI) and varices of the legs were selected and double-blindly randomly assigned to a treatment with Pycnogenol (French maritime pine bark extract), 100 mg x 3/day or a placebo for 2 months, according to a double-blind experimental design. The effects of the treatment were evaluated by scoring the symptomatology with a semi-quantitative scale, and the venous blood flow by means of a hand-held Doppler ultrasound. The tolerability was evaluated by recording the adverse effects and by means of hematology and blood chemistry parameters, before and at the end of the treatment. Pycnogenol treatment induced a significant reduction in subcutaneous edema as well as heaviness and pain in the legs, on both after 30 and 60 days, the evaluation time periods. Approximately 60% of patients treated with Pycnogenol(R) experienced a complete disappearance of edema (the most rapidly disappearing symptom) and pain at the end of the treatment, while almost all the patients reported a reduction in leg heaviness which disappeared in approximately 33% of patients. These changes were statistically significant. No effect was observed in the placebo-treated subjects. No effect on the venous blood flow was observed in either of the experimental groups. Diseases of the venous system are widespread disorders sometimes associated with modern civilisation and are among the major concerns of social and occupational medicine. This study was carried out to compare the efficacy (oedema reduction) and safety of compression stockings class II and dried horse chestnut seed extract (HCSE, 50 mg aescin, twice daily).
                Equivalence of both therapies was examined in a novel hierarchical statistical design in 240 patients with chronic venous insufficiency. Patients were treated over a period of 12 weeks in a randomised, partially blinded, placebo-controlled, parallel study design.
                Lower leg volume of the more severely affected limb decreased on average by 43.8 mL (n = 95) with HCSE and 46.7 mL (n = 99) with compression therapy, while it increased by 9.8 mL with placebo (n = 46) after 12 weeks therapy for the intention-to-treat group (95% CI: HCSE: 21.1-66.4; compression: 30.4-63.0; placebo: 40.0-20.4). Significant oedema reductions were achieved by HCSE (p = 0.005) and compression (p = 0.002) compared to placebo, and the two therapies were shown to be equivalent (p = 0.001); in this design, however, compression could not be proven as standard with regard to oedema reduction in the statistical test procedure. Both HCSE and compression therapy were well tolerated and no serious treatment-related events were reported.
                These results indicate that compression stocking therapy and HCSE therapy are alternative therapies for the effective treatment of patients with oedema resulting from chronic venous insufficiency. The optimal treatment of superficial thrombophlebitis of the leg is undefined. The main study objective was to assess the efficacy and safety of unmonitored high doses as compared to low doses of unfractionated heparin (UFH) for prevention of venous thromboembolic complications in patients with superficial thrombophlebitis of the thigh.
                Sixty consecutive patients with acute thrombophlebitis of the great saphenous vein, as assessed by ultrasonography, were randomized to subcutaneous injection twice daily of UFH in high unmonitored doses (12,500 IU for one week followed by 10,000 IU) or prophylactic doses (5,000 IU) for four weeks. The rate of asymptomatic involvement of the deep venous system and/or symptomatic thromboembolic events during a six-month follow-up period was assessed and compared between the two study groups.
                Six of the 30 patients (20.0 %; 95% CI, 7.7 to 38.6) randomized to low-dose UFH developed symptomatic or asymptomatic events as compared to 1 of the 30 patients (3.3%; 95% CI, 0.07 to 17.2) who received high-dose UFH (p=0.05 by one-sided Fisher's exact test). No patient experienced major bleeding complications in either group.
                The results of this study suggest that in patients with acute thrombophlebitis of the thigh unmonitored high doses of UFH are more effective than prophylactic doses of UFH for prevention of venous thromboembolic complications and do not enhance the risk of bleeding complications. In a randomized placebo controlled parallel double blind study on 40 patients suffering from venous edema in chronic deep vein incompetence, the edema-reducing effect of horse chestnut seed extract vs. placebo, being the main test variable, was demonstrated by hydroplethysmography to be statistically significant. In addition, measurements of leg volume under aggravated conditions (edema provocation) were conducted, which yielded the same results. Additional measurements of leg circumference tendentially confirm the demonstrated clinical efficacy of verum, as is true for phlebody-namometric measurements (pressure at rest, minimum pressure, replenishment time) as well. By measuring the leg volume before and after edema provocation, it could be shown that the clinical benefit for the patient is present in all everyday situations (in movement as well as on sitting or standing). Treatment with an edema protective agent of the horse chestnut seed extract type is thus a useful adjunct to compression therapy. The tested preparation were well tolerated. The involvement of the microcirculation in chronic venous insufficiency (CVI), due to venous hypertension, causes venous hypertensive microangiopathy (VHM) and ulceration. VHM is characterized by enlarged, convoluted capillaries; microvascular thrombosis; obliteration of some capillaries; increase in flux, permeability, and edema and altered microlymphatics. PO2 is decreased and CO2 increased. Capillary exchanges are altered and nutritional alterations eventually lead to venous ulcers. Edema is associated with increased capillary pressure, reduced clearance, and increased exchange surface of capillaries, which become tortuous and glomerular-like. The aim of this randomized, placebo-controlled study was to evaluate local treatment with Essaven gel (EG) in subjects with venous microangiopathy and ulcers. Measurements of laser Doppler flux, PO2, and PCO2 in standardized conditions showed positive changes (a significant decrease of the abnormally increased flux and CO2 while PO2 increased) in the EG treatment group. Changes in the placebo and control group were more limited (changes in the placebo group were mainly associated with skin manipulation when placebo-EG was applied). In conclusion, Essaven gel, in comparison with placebo, acutely improves the microcirculation in VHM even with a single acute application. The aim of this study was to evaluate the effect of hydroxyethylrutosides on capillary filtration in subjects with mild to moderate venous incompetence--superficial varicose veins and/or deep venous disease and ankle oedema--using the vacuum suction chamber (VSC) device applied to the internal perimalleolar region and the wheal vanishing (WV) time. Subjects entered in to the study were randomised to receive either hydroxyethylrutosides (1 g twice daily for 4 weeks) or placebo for four weeks. The two groups entering and completing the study were comparable. Microcirculatory parameters (laser-Doppler resting flux, the venoarteriolar response, transcutaneous PO2 and PCO2) remained constant during the four week study in both groups. The WV time, which was comparable in the two groups at the beginning of the study decreased significantly [from a median 55 min (interquartile 955 min), to a median 45 minutes (interquartile 65-40 min) in the treated group, p < 0.01]. No change was observed in the WV time in the placebo group. Subjective symptoms measured with an analogue scale improved following treatment with hydroxyethylrutosides [foot oedema (p < 0.005), ankle oedema (p < 0.001), and paraesthesia (p < 0.01)]; only night cramps were reported less in patients receiving the placebo (p < 0.05). In conclusion, the WV time can be used to assess the beneficial effect of therapy on capillary filtration in subjects with mild-moderate venous hypertension, even after a short period of treatment, and before other microcirculatory parameters change. Furthermore, the changes observed in WV time correlate well with an improvement in patients symptoms. Oxerutins (O-(beta-hydroxyethyl)rutosides, HR, Venoruton) and horse chestnut extract (HCE) are active principles of first priority for the pharmacological treatment of chronic venous insufficiency (CVI). The efficacies of both compounds were shown in numerous, double-blind, randomized, placebo controlled clinical trials. Besides the direct comparison of the two compounds the aim of the study was to investigate the initial dose/maintenance dose concept for HR. 137 female, postmenopausal patients with CVI II finished the study according to protocol. Following one week placebo run-in the patients were treated either with 1000 mg/d HR, 600 mg/d HCE or 1000 mg/d for 4 weeks and than with 500 mg/d HR within the initial dose/maintainance dose concept for 12 weeks and observed for further 6 weeks. A main confirmative criterion was the volume reduction of the leg. Subjective criteria were descriptively evaluated. HR (1000 mg/d) was proven to be equivalent or better, reducing the leg volume (AUB0-18) by -5273 +/- 11418 ml.d compared to -3187 +/- 10842 ml.d under HR (1000 mg/d and 500 mg/d), and -3004 +/- 7429 ml.d under HCE-treatment. Both compounds exhibit a substantial carry-over effect. The maintenance posology of HR is able to stabilize the therapeutic obtained under initial dose conditions. Ninety patients with venographically proven deep venous thrombosis(DVT) but without clinical signs of pulmonary embolism(PE) were randomized into two different treatment regimens to compare the safety and efficacy of continuous intravenous heparin and oral anticoagulant(AC) treatment versus non-AC treatment. All patients in the two treatment groups were actively mobilized from the day of admission and wore graduated compressing stockings. In the non-AC-group the patients were treated with phenylbutazone for ten days. Treatment with heparin was maintained for 6 days and oral AC treatment was given from the third day and continued for 3 months. Venography was repeated after 30 days. A perfusion-ventilation lung scan was performed on day 1-2, 10 and 60. In fifty-nine patients a revenography was performed, twenty nine in the AC-group and thirty in the non-AC group. For distal veins regression was found in nine and eight respectively (4.4% in favour of AC, 95% confidence limit 27.5% to -18.7%) and in proximal veins regression was found in five and eight, respectively (10.9% in favour of AC, 95% confidence limit 32.0% to -10.1%). No difference in lung scans was found after 10 days (0.8% in favour of AC, 95% confidence limit 21.5% to -19.9%) or after 60 days (3.3% in favour of non-AC treatment, 95% confidence limit 21.8% to -28.5%). In the AC group the incidence of bleeding complications was 8.3%. No side-effects of phenylbutazone was found. The present controlled clinical study demonstrated no effect of AC-treatment on DVT progression in actively mobilized patients wearing graduated compressing stockings when compared to a non-AC treated group receiving analgetic therapy with phenylbutazone. However, the patient population of the study is relatively small with wide confidence intervals for differences between groups. Before more general recommendations can be made, a large scale placebo-controlled study is needed to evaluate the possible effect of AC-treatment in DVT patients, who can be mobilized from the first day. One hundred fifty patients over the age of 30 who had undergone major abdominal operations were stratified according to the risk of deep venous thrombosis and randomized into three groups to receive different prophylactic regimens: group A, electrical calf stimulation; group B, low-dose subcutaneous heparin; group C, intermittent sequential compression and thromboembolism-deterrent (TED) stockings. All the patients were scanned with the 125I-fibrinogen test for the whole stay in hospital. The incidence of 125I-fibrinogen detected deep venous thrombi was 18% in group A, 9% in group B, and 4% in group C. The results indicate that the regimen of intermittent sequential compression and TED stockings is as effective as low-dose subcutaneous heparin. Electrical calf stimulation is less effective. The aim of the present study was to evaluate the effects of different treatment plans (compression only, early surgery, low-dose subcutaneous heparin [LDSH], low-molecular-weight heparin [LMWH], and oral anticoagulant [OC] treatment) in the management of superficial thrombophlebitis (STP), by considering efficacy and costs in a 6-month, randomized, follow-up trial. Patients with STP, with large varicose veins without any suspected/documented systemic disorder, were included. Criteria for inclusion were as follows: presence of varicose veins; venous incompetence (by duplex); a tender, indurated cord along a superficial vein; and redness and heat in the affected area. All patients were ambulatory. Exclusion criteria were obesity, cardiovascular or neoplastic diseases, bone/joint disease, problems requiring immobilization, and age > 70 years. Patients with superficial thrombophlebitis without varicose veins and patients under treatment with drugs at referral were also excluded. Color duplex (CD) was used to detect concomitant deep vein thrombosis (DVT) and to evaluate the extension or reduction of STP at 3 and 6 months. Venography was not used. Of 562 patients included, 3.5% had had a recent DVT in the same limb affected by SVT and 2.1% in the contralateral limb. In six patients DVT was present in both limbs. These patients were treated with anticoagulants and excluded from the follow-up. After 3 and 6 months the incidence of STP extension was higher in the elastic compression and in the saphenous ligation groups (p < 0.05). There was no significant difference in DVT incidence at 3 months among the treatment groups. Stripping of the affected veins was associated with the lowest incidence of thrombus extension. The cost for compression alone was the lowest and the cost including LMWH was the highest. The average cost was 1,383 US$. However the highest social cost (lost working days, inactivity) was observed in subjects treated only with stockings. In 20 patients with chronic venous insufficiency and venous hypertension associated with ulcerations, the effects of a new compound, applied onto the skin (Crystacide) were assessed in a randomized, controlled study. Duplex scanning was used to assess the presence of venous obstruction and incompetence, and microcirculatory methods were used to assess and quantify venous microangiopathy and to follow up subjects after local treatment with Crystacide. Laser Doppler flowmetry (LDF) was used to assess skin perfusion in association with transcutaneous (tc) partial pressure of oxygen (PO2) measurements. Local plasma free radicals (PFR) were evaluated in the area surrounding the venous ulcer, with the D-Rom test. Crystacide was applied around and on the ulcer for 10 days. Crystacide was more effective than the control treatment: PO2 was increased, PFR and LDF were decreased (flux increase is associated with venous hypertension), and the ulcer area was significantly smaller at 10 days in the Crystacide group in comparison with the placebo group (p<0.05). In conclusion, in venous ulcerations, local treatment with Crystacide (10 days) improves the microcirculation and decreases skin free radicals improving healing. Pneumatic compression stocking (PCS) devices have been introduced to decrease the incidence of postoperative deep venous thrombosis (DVT). However, their role in the prophylaxis against pulmonary embolism (PE) remains unclear. This study was undertaken to compare the prophylactic effectiveness of subcutaneous heparin (SCH) alone vs the combined use of PCS and SCH in the prevention of PE following cardiac surgery.
                We studied 2,551 consecutive patients who underwent cardiac surgery over a 10-year period. They were randomly allocated to two groups. Group A included 1,196 patients who were treated with 5,000 U of SCH every 12 h and group B included 1,355 patients treated with a combined prophylactic regimen of PCS and SCH.
                The diagnosis of PE was established in 69 patients by either high-probability ventilation perfusion scan, pulmonary angiogram, or autopsy. The incidence of PE in group A patients was 4% (48/1,196) and in group B was 1.5% (21/1,355). The concomitant use of bilateral PCS and SCH reduced the frequency of postoperative PE in 62% in comparison to the prophylaxis with SCH alone (p < 0.001).
                These data suggest that the combined prophylactic method of bilateral PCS and SCH is superior to SCH alone in the prevention of PE after cardiac surgery. The true incidence of postphlebitic syndrome (PPS) following proximal deep venous thrombosis (DVT) and the efficacy of graduated compression stockings in preventing and treating PPS are unknown.
                A 3-part study of 202 patients evaluated 1 year after proximal DVT: 2 randomized placebo-controlled trials of stockings and 1 prospective cohort of untreated patients. Patients were evaluated for PPS, using a standardized questionnaire, and for venous valvular incompetence, using photoplethysmography and venous Doppler. They were enrolled in study 1 or study 2 if they did not have symptomatic PPS and did not have or had venous valvular incompetence, respectively, and into study 3 if they had symptomatic PPS. Study 1 patients were left untreated and followed up for development of PPS every 6 months for a mean of 55 months. Study 2 patients were randomized to a below-knee stocking (20-30 mm Hg) or a matched placebo stocking, and followed up for development of PPS every 6 months for a mean of 57 months. Study 3 patients were randomized to an active stocking (30-40 mm Hg) or a matched placebo stocking and followed up every 3 months for treatment failure, defined a priori.
                In study 1, 6 (5.0%) of 120 patients were categorized as treatment failures, a rate similar to placebo-treated study 2 patients (P =.10). In study 2, 0 (0%) of 24 active and 1 (4.3%) of 23 placebo-treated patients were categorized as treatment failures (P =.49). In study 3, 11 (61.1%) of 18 active and 10 (58.8%) of 17 placebo-treated patients were categorized as treatment failures (P>.99).
                Most patients do not have PPS 1 year after proximal DVT, and do not require stockings. We failed to show a benefit of stockings in patients with PPS, but the small numbers preclude definitive conclusions. Epidemiological data show that standard compression therapy for leg ulceration in chronic venous insufficiency (CVI) often fails to effectively improve patients' condition. This study assesses the contribution of Daflon 500 mg added to conventional therapy in the healing of hypostatic ulcers of CVI patients.
                Patients of about 65 years were included, with ulcers > or = 2 and > or = 10 cm diameter on 1 or 2 limbs, Doppler ankle/arm pressure index > 0.9, and no recent history of skin graft. Controls (n=68) remained on compression alone while the tested group (n=82) also received Daflon 500 mg 2 tablets/day during 6 months. Treatment could be stopped as soon as the reference ulcer appeared fully healed. Primary endpoints were the rate of healed ulcers and the time to complete healing assessed by planimetry/photography and clinical examination. Variations of the ulcer surface, appearance of the skin, and clinical symptoms of CVI were the secondary criteria.
                Only 7% of Daflon 500 mg patients necessitated the full 6 month therapy. Whatever the lesion size, from W8 significantly more healed ulcers were observed under Daflon 500 mg (p=0.004), and the ulcer surface was more reduced (p=0.012). For large ulcers, the rate of healing was approximately 2-fold higher with Daflon 500 mg, and the percentage of ulcers healed before W24 was significantly higher (p=0.008). Heavy leg sensation was significantly improved by Daflon 500 mg from W4 (p < 0.05). No treatment-related side effects were reported and the acceptability was considered excellent by 85% of Daflon 500 mg patients.
                Six months of Daflon 500 mg in addition to compression significantly improve some clinical symptoms and accelerate the healing process in patients with ulcerous complications of CVI, with a good acceptability. A prospective, randomized study was conducted to compare the performance of 2 hydrocolloid dressings, hydrocolloid A and hydrocolloid B, in the treatment of venous insufficiency ulcers. A total of 31 patients were enrolled at 2 clinical sites. Complete wound closure (100% epithelialization) was observed in 59% of the patients treated with hydrocolloid A, compared with complete wound closure in 15% of the patients in the hydrocolloid B group (P <or=.03). Investigators also rated hydrocolloid A significantly better in ease of application, adhesion, conformability, exudate absorption, barrier properties, transparency, and patient comfort (P <or=.02). Significantly fewer patients in the hydrocolloid A group required unscheduled, product-related dressing changes (P <or=.02). In this clinical study, hydrocolloid A demonstrated excellent performance characteristics and was highly effective in treating venous insufficiency ulcers. In 32 patients with chronic venous insufficiency and venous hypertension associated with ulcerations, the effects of the local application of a hydrogen peroxide cream (Crystacide) applied onto the skin was evaluated using a complex, proportional, microcirculatory model to assess and quantify venous microangiopathy after local treatment. A comparative group treated without Crystacide was included. Laser Doppler flowmetry was used to assess skin perfusion (flux and venoarteriolar response) in association with transcutaneous PO2 and PCO2 measurements. Local plasma free radicals were evaluated in the area surrounding the venous ulcer using the D-Roms test. Crystacide was applied around and on the ulcer for 10 days. Crystacide was more effective than the control treatments. PO2 was increased (improved, P < .05), and plasma free radicals, PCO2, and laser Doppler flowmetry were decreased (improving toward normal values, P < .05). Also, the ulcerated area was significantly smaller at 10 days in the Crystacide group in comparison with controls (P < .05). In the proportional microcirculatory model, all parameters indicated an important level of improvement significantly larger than in controls. In conclusion, in chronic venous insufficiency and venous ulcerations, local treatment with Crystacide (10 days) improves the microcirculation and decreases skin free radicals, thus improving healing.
There is not enough evidence to globally support the efficacy of phlebotonics for chronic venous insufficiency. There is a suggestion of some efficacy of phlebotonics on oedema but this is of uncertain clinical relevance. Due to the limitations of current evidence, there is a need for further randomised, controlled clinical trials with greater attention paid to methodological quality.