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Background: In this pilot non-interference clinical study we evaluated possible interactions between Quercetin Phytosome® (Quercefit™), an innovative delivery form of quercetin, and antiplatelet agents, anticoagulants, and anti-diabetic therapy in otherwise healthy subjects., Methods: Interaction with antiplatelet therapy was assessed through the bleeding time (BT) test in 30 patients treated with acetylsalicylic acid, ticlopidine or clopidogrel before and after 10 days of supplementation with Quercetin Phytosome®. Interaction with anticoagulants was evaluated by measuring the International Normalized Ratio (INR) in 20 patients using warfarin or dabigatran before and after 20 days of supplementation with Quercetin Phytosome®. Lastly, glycaemia and glycated hemoglobin were measured in 12 diabetic patients treated with metformin and restricted diet before and after 20 days of supplementation with Quercetin Phytosome®., Results: After 10 days of supplementation no significant difference was observed in mean BT in patients treated with acetylsalicylic acid, ticlopidine or clopidogrel at standard dosages. Similarly, after 20 days of supplementation, the INR level among patients assuming warfarin or dabigatran was not statistically different from baseline. Lastly, no statistically significant difference in mean levels of glycaemia and glycated hemoglobin was reported before and after 20 days of complementary administration of Quercetin Phytosome® in diabetic patients treated with metformin and restricted diet., Conclusions: Quercetin Phytosome® does not alter the antiplatelet activity of the most common antiplatelet agents, has no impact on the INR values in stable patients treated with warfarin or dabigatran, and does not influence the metabolic control of diabetic patient treated with metformin.

Objective: The objective of this clinical study is to evaluate possible interactions between antiplatelet agents, anticoagulants, thyroid hormone replacement therapy and a formulation of curcumin (Meriva®) that resulted effective for the complementary treatment of osteoarthritis., Patients and Methods: Interaction between antiplatelet agents and Meriva® was evaluated by measuring anti-platelet activity with the in-vivo bleeding-time (BT) in patients assuming acetylsalicylic acid or ticlopidine or clopidogrel from at least 2 years. The BT was evaluated before and after 10 days of supplementation with Meriva®. The interaction between anticoagulants and Meriva® was evaluated in patients using warfarin or dabigatran for previous venous thrombosis. The INR level was evaluated before and after 10 days of supplementation with the curcumin formulation. Thyroid function tests in hypothyroid patients using LT4 replacement therapy (Eutirox®) were evaluated before and after 15 days of supplementation with Meriva®. Similarly, levels of glycemia and glycated hemoglobin were evaluated in diabetic patients in treatment with metformin, before and after 10 days of supplementation with the studied product., Results: After 10 days of supplementation with Meriva® the average BT value was not significantly different for patients assuming acetylsalicylic acid, ticlopidine or clopidogrel at standard dosages. Similarly, after 10 days of Meriva® treatment, the INR level in the two groups of patients assuming warfarin or dabigatran was not statistically different from that observed at baseline. In the analyzed patients assuming LT4 or metformin, no interactions between the therapy and Meriva® were observed., Conclusions: Results from this non-interaction clinical study suggest that Meriva® does not interfere with the antiplatelet activity of the most common antiplatelet agents nor alters the INR values in stable patients assuming warfarin or dabigatran. Similarly, dosages of LT4 or metformin do not need to be adjusted in case of complementary treatment with Meriva®.

Aim: The aim of this open, observational registry was to evaluate the effects of antithrombotic treatment on the development of postthrombotic syndrome (PTS): the effects of "standard management" (SM; according to International Union of Angiology guidelines) were compared to SM in association with sulodexide or aspirin., Methods: Postthrombotic syndrome occurrence was observed in 3 nonparallel groups after deep venous thrombosis (DVT); the registry started after the end of the anticoagulation period. The target was to observe the occurrence of PTS in 5 years. Three possible options were suggested to the patients, and the patients and their caregivers defined the type of management. A group of 167 patients was involved in the SM with reevaluation every 6 months; the sulodexide group included 124 patients and the aspirin group included 48 patients., Results: The 3 groups were clinically similar and comparable for age and sex distribution. Of the 167 patients in the SM group, 154 patients completed 60 months of follow-up. The percentage of patients with PTS in the SM group ranged from 14.9% (1 year after the end of anticoagulation) to 19.5% (60 months). In the nonparallel group using sulodexide (124 comparable patients at inclusion; 115 at 60 months), the percentage of PTS was variable from 8.8% (1 year after anticoagulants) to 12.17% at 60 months. These percentages are significantly lower than those observed with SM. In the nonparallel aspirin group (48 patients at inclusion and 34 at 54 months), there was a PTS incidence of 23.5% at 54 months (vs 12.17% in the sulodexide group and 18.23% in the SM group). The incidence of PTS was significantly higher in comparison with the other 2 groups. The incidence of PTS was lower in the sulodexide group in comparison with the 2 other groups., Conclusions: Sulodexide administration after DVT appears to be effective in preventing PTS in association with recommended management and a number of recurrent DVTs. Modalities of treatment, dosages, and timing of administration should be explored in more comprehensive and complete studies., (© The Author(s) 2014.)

The evolution of microcirculatory methods and the definition of the concept of venous microangiopathy allow the study in a quantitative way of microcirculatory changes produced by pharmacologic treatments at the areas most frequently and severely affected by chronic venous insufficiency (CVI), venous hypertensive microangiopathy, and venous ulcerations. This pilot study compares subjects with CVI, in the area most affected by venous hypertension in a 2-week registry. Elastic compression, compression plus Viatromb (lyposomal spray gel heparin), Lioton (gel including heparin), and Viatromb alone were compared. Subjects were evaluated for laser Doppler flux, transcutaneous partial pressure of oxygen (TcPO2), and partial pressure of carbon dioxide (PCO2) and CVI analogic symptom scale. In the Viatromb groups (B and D), significant decreases in laser Doppler flux, PCO2, and CVI score were observed. The decrease was proportionally more important in the elastic compression plus Viatromb group. Partial pressure of oxygen (PO2) was significantly increased. No significant changes were observed in the Lioton group. There was a good effect for compression only. These differences are significant, as they can be observed even in small groups (10-15 patients). No treatment side effects were observed, and compliance and tolerability were very good.

Topical effects of heparins on the skin need deeper investigations. The lack of evidence is mainly due to the lack of large investments in this field. Three main local actions of heparin on the skin can be defined: (a) the anticoagulant action, (b) the microcirculatory-modulatory action determining important control of the microcirculation in case of excessive vasoconstriction or vasodilatation, and (c) the 'facilitatory action' on skin permeability allowing other drugs to diffuse better and faster into the skin (producing a therapeutic effect). These aspects have to be evaluated more extensively in both experimental and clinical conditions. Recent experimental studies demonstrate these effects of locally applied heparin. Therefore, key questions on local heparin administration such as skin penetration and the action on the local thrombi have promising answers. These observations suggest important clinical applications for local liposomal heparin. Both the potentials of local applications of heparin, particularly with new formulations, and some new aspects in the management of superficial vein thrombosis (SVT) can focus on locally applied heparin. SVT is an important clinical condition considering its frequency and the potentially heavy use of local heparin in this clinical problem. Results from new studies and observations presented in this issue of Angiology could be a window for suggesting new significant clinical applications and therapeutic solutions.

The aim of this independent study was to investigate differences in efficacy between oxerutins (Venoruton) and 500 mg micronized diosmin + hesperidin (D+H) (Daflon) in patients with chronic venous insufficiency (CVI), evaluating venous-related quality of life (Ve-QOL). A first group of 90 patients with severe venous hypertension (CVI, ankle swelling) was randomized to treatment with oxerutins or D+H. The oxerutins group received oral oxerutins (2 g/day); the D+H group received 3 (500 mg) tablets daily every 8 hours for 8 weeks. A second group of 122 comparable patients was included in a registry following the same study format. The 2 treatments were administered with the same methods and procedures. Clinical conditions were comparable. All patients completing 8 weeks of treatment were included in a registry. Specialists or general practitioners included patients when they considered that clinical conditions were compatible with treatment indications using 1 of the 2 treatments on the basis of their evaluation and experience. When cases were compatible with the registry, the prescribing physician communicated the case to our monitoring center. Patients were evaluated without interfering with their treatment. The main target of evaluation for this study was the change in Ve-QOL (range, 0-100) induced by treatment. A specific Ve-QOL questionnaire was used for this study. Ve-QOL score is a specific expression of the changes in QOL induced by CVI in patients between 35 and 75 years old (defined in our population studies) in which no other significant clinical disease is present (as a confounding factor affecting QOL). Two hundred twelve patients completed the 2 parts of the study. The 2 treatment groups were comparable for age and gender distribution. The mean age was 42 years (SD +/-5.5) in the oxerutins group and 41.5 (SD +/-6) in the D+H group. There were no differences in the severity of CVI between the treatment groups at inclusion. A significant decrease (46.8%, p <0.05) in Ve-QOL score; that is, improvement, was observed in the oxerutins group. The change in Ve-QOL was significantly less in the D+H group (15.5%). In conclusion, CVI, venous microangiopathy, and edema were significantly improved by the treatment with oxerutins; the improvement in QOL was significantly greater in the oxerutins group. The comparison with D+H indicates that oxerutins is comparatively more effective on Ve-QOL and on signs/symptoms of CVI.

A medicated plaster containing diclofenac epolamine (DHEP) and heparin has been recently proposed for the treatment of local trauma (ie, ankle sprains) accompanied by a clinically significant edema and/or hematoma formation, based on the combined antiinflammatory, hemorheologic, and antiedema properties of diclofenac and heparin. The aim of this study was therefore to compare the effects of a combined DHEP/heparin and DHEP alone in 2 clinical experimental models of microangiopathy, in order to provide a pharmacologic rationale for association of diclofenac and heparin. The microcirculation was evaluated by measuring cutaneous blood flow (laser Doppler) and transcutaneous oxygen and carbon dioxide pressures (TcPO(2) and TcPCO(2)) in 10 healthy volunteers before and after producing 2 microcirculatory models of microangiopathy: the models were based on reactive hyperemia (RH) and on local histamine injection, which both produce a significant increase in skin flux and alterations of TcPO(2) and TcPCO(2). The area of the study was the distal medial leg, treated with placebo, DHEP alone (Flector Tissugel), and DHEP/heparin (Flector Tissugel Heparin). The plasters were applied before producing the microcirculatory models to evaluate the efficacy of DHEP and DHEP/heparin in controlling and limiting vasodilatation and development of microangiopathy. A significant increase in cutaneous flux was obtained with both models. The application of DHEP partially limited the increase in flux and in TcPCO(2), as well as the decrease in TcPO(2) (which were considered signs of microangiopathy), but the combination DHEP/heparin was significantly more effective than DHEP alone. The inclusion of heparin in the plaster thus improved the control of the microcirculation achieved with diclofenac alone, when an experimental model of venous/arterial hyperemia and microangiopathy was used. In conclusion, DHEP in association with heparin modulates microcirculatory changes better than DHEP alone. It should be interesting to investigate the product in comparable clinical conditions in which it may be useful to act pharmacologically both on inflammation and microcirculatory disturbances that delay the recovery of patients.

The aim of this study was to evaluate the prevention of recurrent deep vein thrombosis (R-DVT) with an oral antithrombotic agent (sulodexide) in moderate to high-risk subjects. A group of 405 patients was included into the multicenter registry. Both compression and an exercise program were used as well as a risk-factors control plan. After diagnosis of DVT, patients were treated with oral anticoagulants for 6 months. At the end of this period a coagulation study was made and patients started treatment with oral sulodexide capsules for a period of 24 months. The femoral, popliteal, tibial, and superficial veins were scanned with high-resolution ultrasound at inclusion;scans were repeated at 6, 12, 18, and 24 months. Of the 405 subjects included into the registry 178 in the control group (mean age 52.2; SD 11; M:F=90:88) and 189 in the treatment group (mean age 53.2; SD 10.3; M:F=93:96) completed the analysis period of 24 months. At 6 and 12 months the incidence of R-DVT was lower (p<0.05) in the treatment group. At 24 months the global incidence of R-DVT was 17.9% in the control group and 7.4% in the sulodexide group (p<0.05), 2.42 times lower than in controls. The 2 groups were comparable for age and sex distribution and for the localization of the thrombi at inclusion. Also the 2 groups of dropouts were comparable. In the control group there were 32 recurrent DVTs and 24 subjects lost to follow-up (total of 56) of 202 included subjects (27.7%) in comparison with 28 failures (14 recurrent DVTs and 14 lost subjects) of 203 subjects (13.8%) in the treatment group. This difference was statistically significant. In this analysis the incidence of DVT in controls was 2.07 times higher than in the treatment group subjects. In conclusion sulodexide was effective in reducing recurrent thrombotic events in high-risk subjects.

The aim of this study was to confirm the clinical efficacy of oxerutins by evaluation of venous parietal tone and microvascular perfusion in a double-blind, randomized, placebo-controlled study. The study included 60 patients. Venous tone was evaluated by air-plethysmography (APG) in patients with venous insufficiency (CVI). Forty patients were treated with oxerutins and 20 with placebo for 4 weeks. The dose of the first 2 weeks was higher than that of the following 2 weeks. The age range was between 18 and 65 years. Randomized patients received treatment (oxerutins or placebo) according to the grade of CVI. Patients with grade I CVI received 2 g/day in the first 2 weeks of treatment and 1 g/day in the following weeks. Patients with grade II CVI received 3 g/day in the first 2 weeks and 2 g/day in the following 2 weeks. Visits were scheduled at baseline time (visit 1), at 2 weeks (visit 2) and at 4 weeks (visit 3). They were assessed with the following: (1) APG; (2) light reflection rheography (LRR); (3) capillaroscopy; (4) liquid crystals thermography. CVI signs/symptoms--heavy legs, edema, paresthesia, and cramps--were evaluated following a 4-point rating scale (0 = no symptom; 3 = severe symptoms). At visit 3 a final opinion on efficacy was provided by both patients and investigators, based on a 4-point scale (none, fairly good, good, excellent). The two groups were homogeneous for age, sex, and clinical distribution. The changes in venous capacity, were significant (p<0.01) in the oxerutins group at visits 2 and 3; values in the placebo group remained unchanged. The changes in LRR were significant in the treatment group at visits 2 (p<0.05) and 3 (p<0.01); values in the placebo group remained unchanged. Changes in temperature were significant in the oxerutins group at visits 2 (p<0.05) and 3 (p<0.01); changes in the placebo group were not significant at the end of the study. Capillaroscopy showed an improvement in patients treated with oxerutins. The results of the analysis of signs/symptoms favored active treatment. The overall effects of oxerutins were significantly better than the effects of placebo. Considering both noninvasive tests and clinical evaluation, oxerutins is effective in controlling chronic venous hypertension, without side effect, and with good tolerability.

Background: Deep venous thrombosis (DVT) of distal veins of the legs is important for its frequency and its potential proximal extension. The incidence of embolization in distal DVT is limited and treatment still undefined., Methods: After diagnosing with duplex scanning a distal DVT patients were included in a 24-week follow-up. All subjects used elastic compression (stockings TED = thromboembolic deterrent) for 24 weeks after DVT. In the 4 groups the following prophylaxis for 8 weeks were used: A: oral anticoagulant (INR 2.5). B: subcutaneous calcium heparin 0.2 ml bid (8.00 and 20.00). C: subcutaneous calcium heparin (0.5 ml at 20.00). D was the control group (only elastic TED stockings). heparin 0.2 ml bid (5000 IU) and 0.5 ml once daily (12.500 IU) were used for individuals with weight range between 65 and 90 kg. No patient was admitted into hospitals. Initially 106 patients were included. There were 17 (9.6%) drop outs and after 8 weeks 177 patients completed the study. No pulmonary embolisation or side effects were observed. In one patient (control group) an important extension of the thrombus to the femoral and iliac veins was observed., Results: The percentage of thrombus reduction was higher in the treatment groups than in controls (p < 0.05). No significant differences were found among the 3 treatment groups. At 8 weeks 88.6% of patients treated with oral anticoagulant showed improvement (stability/reduction in size of the thrombus; the percentage was 88.4% in subjects treated with subcutaneous heparin bid and 93.2% in those treated with a single dosage). In the control group thrombus increase was observed in 78.3% of patients (this difference was significant in comparison with the treatment groups; p < 0.05). At the 24-week control in 97.6% of patients in group A thrombosis was reduced/stable. This percentage was 97.7% in the ca-heparin double-dose group (B) and 100% in the single dose group (C), significantly lower than in group D (75%; p < 0.05)., Conclusions: Results indicate that untreated subjects with distal DVT are at risk of thrombus extension. In this study treatments were clinically equivalent. However one single dose of subcutaneous heparin is as effective as the double dose, is better tolerated, does not require haematological monitoring and has a lower cost.

Superficial vein thrombosis is characterized by clotting of superficial veins (ie, following direct trauma) with minimal inflammatory components. Superficial thrombophlebitis is a minimally thrombotic process of superficial veins associated with inflammatory changes and/or infection. Treatments generally include analgesics, elastic compression, anti-inflammatory agents, exercise and ambulation, and, in some cases, local or systemic anticoagulants. It is better to avoid bed rest and reduced mobility. Topical analgesia with nonsteroidal, anti-inflammatory creams applied locally to the superficial vein thrombosis/superficial thrombophlebitis area controls symptoms. Hirudoid cream (heparinoid) shortens the duration of signs/symptoms. Locally acting anticoagulants/antithrombotics (Viatromb®, Lipohep®, spray Na-heparin) have positive effects on pain and on the reduction in thrombus size. Intravenous catheters should be changed every 24 to 48 hours (depending on venous flow and clinical parameters) to prevent superficial vein thrombosis/superficial thrombophlebitis and removed in case of events. Low molecular weight heparin prophylaxis and nitroglycerin patches distal to peripheral lines may reduce the incidence of superficial vein thrombosis/superficial thrombophlebitis in patients with vein catheters. In case of superficial vein thrombosis/superficial thrombophlebitis, vein lines should be removed. In neoplastic diseases and hematological disorders, anti-coagulants may be necessary. Exercise reduces pain and the possibility of deep vein thrombosis. Only in cases in which pain is very severe is bed rest necessary. Deep vein thrombosis prophylaxis should be established in patients with reduced mobility. Antibiotics usually do not have a place in superficial vein thrombosis/superficial thrombophlebitis unless there are documented infections. Prevention of superficial vein thrombosis should be considered on the basis of patient's history and clinical evaluation. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate the prevention of edema during long-haul flights with an oral, anti-edema and antithrombotic agent (Pycnogenol®, Horphag, Research Management SA, Geneva, Switzerland) in asymptomatic subjects. The assessment of edema was performed by evaluating an analogue scale, the rate of ankle swelling by strain-gauge derived rate of ankle swelling (RAS), and by assessing the ankle circumference variation. The study included 211 subjects; 169 completed the study (88 in the control group and 81 in the Pycnogenol® group). There were no important differences between the two groups (comparable for age, gender, weight, body mass index, and pattern distribution). The edema score, the RAS, and the circumference at inclusion were also comparable. After the flight in those treated with Pycnogenol®, the edema score was increased only by 17.9% (vs. an increase of 58.3% in the control group) (p<0.05). The RAS, evaluated in 22 subjects in the Pycnogenol® group (age 44.5; SD 8) and in 23 in the control group (age 45; SD 9) was increased on average by 91% in the control group and 36% in the Pycnogenol® group (p<0.05). The variation on circumference at the ankle was 6% in the Pycnogenol® group (11% in the control group; p<0.05). These results indicate a positive effect of Pycnogenol® on edema during long flights when considering subjective and objective data. No unwanted effects were observed. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate the occurrence of deep venous thrombosis (DVT) and superficial vein thrombosis (SVT) and its prophylaxis with an oral anti-edema and antithrombotic agent (Pycnogenol®, Horphag, Research Management SA, Geneva, Switzerland) in long-haul flights, in subjects at moderate to high-risk of DVT and SVT. The study pre-included 244 pre-selected subjects; 211 were included (33 were excluded for several reasons due to logistic problems) and 198 completed the study; 13 subjects were lost for follow-up at the end of the flight, all for non-medical problems (i.e., for difficult connections). All subjects were scanned within 90 minutes before the flight and within 2 hours after disembarking. Subjects were supplemented with 100 mg Pycnogenol® per capsule. Treatment subjects received two capsules between 2 and 3 hours before flights with 250 mL of water; two capsules were taken 6 hours later with 250 mL of water and one capsule the next day. The control group received comparable placebo at the same intervals. The flight duration was on average 8 hours and 15 minutes (SD 55 min) (range, 7.45-12.33). In the control group there were five thrombotic events (one DVT and four superficial thromboses) while only non-thrombotic, localized phlebitis was observed in the Pycnogenol® group (5.15% vs. no events; p<0.025). The ITT (intention to treat) analysis detects 13 failures in the control group (eight lost to follow up + five thrombotic events) of 105 subjects (12.4%) vs. five failures (4.7%; all lost, no thrombotic events) in the treatment group (p<0.025). No unwanted effects were observed. In conclusion, this study indicates that Pycnogenol® treatment was effective in decreasing the number of thrombotic events (DVT and SVT) in moderate-to-high risk subjects, during long-haul flights. [ABSTRACT FROM AUTHOR]