Fondaparinux for the treatment of superficial-vein thrombosis in the legs. High vs. low doses of low-molecular-weight heparin for the treatment of superficial vein thrombosis of the legs: a double-blind, randomized trial. A randomised open-label trial comparing long-term sub-cutaneous low-molecular-weight heparin compared with oral-anticoagulant therapy in the treatment of deep venous thrombosis. A portable pulsed electromagnetic field (PEMF) device to enhance healing of recalcitrant venous ulcers: a double-blind, placebo-controlled clinical trial. Superficial thrombophlebitis of the legs: a randomized, controlled, follow-up study. A comparison of low-molecular-weight heparin and combined therapy of low-molecular-weight heparin with an anti-inflammatory agent in the treatment of superficial vein thrombosis. Comparison of 3 and 6 months of oral anticoagulant therapy after a first episode of proximal deep vein thrombosis or pulmonary embolism and comparison of 6 and 12 weeks of therapy after isolated calf deep vein thrombosis. Venographic comparison of subcutaneous low-molecular weight heparin with oral anticoagulant therapy in the long-term treatment of deep venous thrombosis. High versus low doses of unfractionated heparin for the treatment of superficial thrombophlebitis of the leg. A prospective, controlled, randomized study.
The efficacy and safety of anticoagulant treatment for patients with acute, symptomatic superficial-vein thrombosis in the legs, but without concomitant deep-vein thrombosis or symptomatic pulmonary embolism at presentation, have not been established.
                In a randomized, double-blind trial, we assigned 3002 patients to receive either fondaparinux, administered subcutaneously at a dose of 2.5 mg once daily, or placebo for 45 days. The primary efficacy outcome was a composite of death from any cause or symptomatic pulmonary embolism, symptomatic deep-vein thrombosis, or symptomatic extension to the saphenofemoral junction or symptomatic recurrence of superficial-vein thrombosis at day 47. The main safety outcome was major bleeding. The patients were followed until day 77.
                The primary efficacy outcome occurred in 13 of 1502 patients (0.9%) in the fondaparinux group and 88 of 1500 patients (5.9%) in the placebo group (relative risk reduction with fondaparinux, 85%; 95% confidence interval [CI], 74 to 92; P<0.001). The incidence of each component of the primary efficacy outcome was significantly reduced in the fondaparinux group as compared with the placebo group, except for the outcome of death (0.1% in both groups). The rate of pulmonary embolism or deep-vein thrombosis was 85% lower in the fondaparinux group than in the placebo group (0.2% vs. 1.3%; 95% CI, 50 to 95; P<0.001). Similar risk reductions were observed at day 77. A total of 88 patients would need to be treated to prevent one instance of pulmonary embolism or deep-vein thrombosis. Major bleeding occurred in one patient in each group. The incidence of serious adverse events was 0.7% with fondaparinux and 1.1% with placebo.
                Fondaparinux at a dose of 2.5 mg once a day for 45 days was effective in the treatment of patients with acute, symptomatic superficial-vein thrombosis of the legs and did not have serious side effects. (Funded by GlaxoSmithKline; ClinicalTrials.gov number, NCT00443053.) In contrast with extensive information on the management of deep vein thrombosis of the lower extremities, little is known on the most appropriate treatment of the superficial vein thrombosis (SVT). In a multicenter, prospective, controlled, double-blind, double-dummy clinical trial, 164 consecutive patients with acute SVT of the great saphenous vein were randomized to receive the s.c. administration of either fixed prophylactic doses (2850 a-Xa IU) or body-weight adjusted therapeutic doses of nadroparin once daily for 1 month. The main study outcome was to compare the rate of asymptomatic and symptomatic extension of SVT and/or venous thromboembolic (VTE) complications during a 3-month follow-up period. Of the 81 patients randomized to the prophylactic doses, seven [8.6%; 95% confidence interval (CI), 3.5-17.0] developed SVT progression or VTE complications as compared with six of the 83 (7.2%; 95% CI, 2.8-15.1) allocated to the treatment group (absolute difference, 1.4; 96% CI, -6.9 to 9.7; P = 0.74). No patient in either group developed major bleeding. Our findings suggest that therapeutic doses of low-molecular-weight heparin, administered for 1 month in patients with SVT of the greater saphenous vein do not improve results obtained by prophylactic doses, administered for the same period, over a 3-month follow-up period. To evaluate whether low-molecular-weight heparin (LMWH) could be equally (or more) effective than oral anti-vitamin-K agents (AVK) in the long-term treatment of deep venous thrombosis (DVT).
                A randomised, open-label trial.
                In this trial, 241 patients with symptomatic proximal DVT of the lower limbs confirmed by duplex ultrasound scan were included. After initial LMWH, patients received 6 months of treatment with full therapeutic dosage of tinzaparin or acenocoumarol. The primary outcome was the 12-month incidence of symptomatic recurrent venous thrombo-embolism (VTE). Duplex scans were performed at 6 and 12 months.
                During the 12-month period, six patients (5%) of 119 who received LMWH and 13 (10.7%) of 122 who received AVK had recurrent VTE (p=0.11). In patients with cancer, recurrent VTE tended to be lower in the LMWH group (two of 36 [5.5%]) vs. seven of 33 [21.2%]; p=0.06). One major bleeding occurred in the LMWH group and three in the AVK group. Venous re-canalisation increased significantly at 6 months (73.1% vs. 47.5%) and at 12 months (91.5% vs. 69.2%) in the LMWH group.
                Tinzaparin was more effective than AVK in achieving re-canalisation of leg thrombi. Long-term tinzaparin was at least as efficacious and safe as AVK for preventing recurrent VTE, especially in patients with cancer. 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. 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. The optimal treatment of superficial vein thrombosis (SVT) of the leg has not been determined yet. The aim of this study is to evaluate the efficacy of low-molecular-weight heparin (LMWH) as compared with combined therapy of LMWH with an anti-inflammatory agent in treatment of SVT.
                Fifty patients with SVT of the greater saphenous vein were randomly assigned to be treated with Ca-nadroparin 190 IUAxa/kg in a single dose or with same dose of Ca-nadroparin and 60 mg oral acemetacine twice daily for 10 days. The efficacy of the two treatments to relieve symptoms and signs was evaluated by using visual analogue scale.
                Significant improvements were achieved for both groups after the treatment in terms of all four symptoms (P < 0.001). Treatment scores were in favour of LMWH with anti-inflammatory agent treatment group to relieve all four symptoms. The most significant and remarkable results obtained were for the reduction of pain and local tenderness (P < 0.05). No patient experienced major complications or mortality in either group.
                The results of this study suggest that the combined therapy of LMWH with an anti-inflammatory agent is more effective than LMWH. It may be an important option in the standard treatment of SVT. The optimal duration of oral anticoagulant therapy after a first episode of venous thromboembolism remains controversial.
                We performed an open-label, randomized trial comparing a short oral anticoagulant course (3 months for proximal deep vein thrombosis [P-DVT] and/or pulmonary embolism [PE]; 6 weeks for isolated calf DVT [C-DVT]) with a long course of therapy (6 months for P-DVT/PE; 12 weeks for C-DVT). The outcome events were recurrences and major, minor, or fatal bleeding complications. A total of 736 patients were enrolled. There were 23 recurrences of venous thromboembolism in the short treatment group (6.4%) and 26 in the long treatment group (7.4%); the 2 treatment regimens had an equivalent effect. For the hemorrhage end point, the difference between the short and the long treatment groups was not significant: 15.5% versus 18.4% for all events (P=0.302), 1.7% versus 2.8% (P=0.291) for major events, and 13.9% versus 15.3% for minor bleeding. Subgroup analysis demonstrated that the rate of recurrence was lower for C-DVT than for P-DVT or PE.
                After isolated C-DVT, 6 weeks of oral anticoagulation is sufficient. For P-DVT or PE, we demonstrated an equivalence between 3 and 6 months of anticoagulant therapy. For patients with temporary risk factors who have a low risk of recurrence, 3 months of treatment seems to be sufficient. For patients with idiopathic venous thromboembolism or permanent risk factors who have a high risk of recurrence, other trials are necessary to assess prolonged therapy beyond 6 months. The primary objective of this study was to evaluate with venography the rate of thrombus regression after a fixed dose of low-molecular weight heparin (LMWH) per day for 3 months compared with oral anticoagulant therapy for deep venous thrombosis (DVT). Secondary endpoints were the comparisons of the efficacy and safety of both treatments.
                This study was designed as an open randomized clinical study in a university hospital setting. Of the 165 patients finally enrolled in the study, 85 were assigned LMWH therapy and 80 were assigned oral anticoagulant therapy. In the group randomized to oral anticoagulant therapy, the patients first underwent treatment in the hospital with standard unfractionated heparin and then coumarin for 3 months. Doses were adjusted with laboratory monitoring to maintain the international normalized ratio between 2.0 and 3.0. Patients in the LMWH group were administered subcutaneous injections of fixed doses of 40 mg enoxaparin (4000 anti-Xa units) every 12 hours for 7 days, and after discharge from the hospital, they were administered 40 mg enoxaparin once daily at fixed doses for 3 months without a laboratory control assay. A quantitative venographic score (Marder score) was used to assess the extent of the venous thrombosis, with 0 points indicating no DVT and 40 points indicating total occlusion of all deep veins. The rate of thrombus reduction was defined as the difference in quantitative venographic scores after termination of LMWH or coumarin therapy as compared with the scores obtained on the initial venographic results. The efficacy was defined as the ability to prevent symptomatic extension or recurrence of venous thromboembolism (documented with venograms or serial lung scans). The safety was defined as the occurrence of hemorrhages.
                After 3 months of treatment, the mean Marder score was significantly decreased in both groups in comparison with the baseline score, although the effect of therapy was significantly better after LMWH therapy (49.4% reduction) than after coumarin therapy (24.5% reduction; P <.001). LMWH therapy and male gender were independently associated with an enhanced resolution of the thrombus. A lower frequency of symptomatic recurrent venous thromboembolism was also shown in patients who underwent treatment with LMWH therapy (9.5%) than with oral anticoagulant therapy (23.7%; P <.05), although this difference was entirely a result of recurrence of DVT. Bleeding complications were significantly fewer in the LMWH group than in the coumarin group (1. 1% vs 10%; P <.05). This difference was caused by minor hemorrhages. Coumarin therapy and cancer were independently associated with an enhanced risk of complications. Subcutaneous heparin therapy was well tolerated by all patients.
                The patients who were allocated to undergo enoxaparin therapy had a significantly greater improvement in their quantitative venographic score, a significantly lower recurrence rate of symptomatic venous thromboembolism, and a significantly lower incidence of bleeding than patients who underwent treatment with coumarin. LMWH can be used on an outpatient basis as a safer and more effective alternative to classical oral anticoagulant therapy for the secondary prophylaxis of selected patients with DVT. 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.
Prophylactic dose fondaparinux given for six weeks appears to be a valid therapeutic option for ST of the legs. The evidence on oral treatments, topical treatment, or surgery is too limited and does not inform clinical practice about the effects of these treatments in terms of VTE and ST progression. Further research is needed to assess the role of the new oral direct thrombin and activated factor-X inhibitors, LMWH, and NSAIDs; the optimal doses and duration of treatment; and whether a combination therapy may be more effective than single treatment. Adequately designed and conducted studies are required to clarify the role of topical and surgical treatments.