Subcutaneous low-molecular-weight heparin compared with continuous intravenous heparin in the treatment of proximal-vein thrombosis. Fixed-dose, body weight-independent subcutaneous LMW heparin versus adjusted dose unfractionated intravenous heparin in the initial treatment of proximal venous thrombosis. EASTERN Investigators. Fixed-dose, body weight-independent subcutaneous low molecular weight heparin Certoparin compared with adjusted-dose intravenous unfractionated heparin in patients with proximal deep venous thrombosis. Low-molecular-weight heparin in the treatment of patients with venous thromboembolism. The Columbus Investigators. Comparison of once-daily subcutaneous Fragmin with continuous intravenous unfractionated heparin in the treatment of deep vein thrombosis. [A new treatment of deep venous thrombosis: low molecular weight heparin fractions. Randomized study]. Efficacy of a low molecular weight heparin administered intravenously or subcutaneously in comparison with intravenous unfractionated heparin in the treatment of deep venous thrombosis. Certoparin-Study Group. Effects of a low-molecular-weight heparin on thrombus regression and recurrent thromboembolism in patients with deep-vein thrombosis. Abbreviated hospitalization for deep venous thrombosis with the use of ardeparin. Once-daily subcutaneous dalteparin, a low molecular weight heparin, for the initial treatment of acute deep vein thrombosis. Subcutaneous enoxaparin once or twice daily compared with intravenous unfractionated heparin for treatment of venous thromboembolic disease. Treatment of venous thrombosis with intravenous unfractionated heparin administered in the hospital as compared with subcutaneous low-molecular-weight heparin administered at home. The Tasman Study Group. A comparison of low-molecular-weight heparin with unfractionated heparin for acute pulmonary embolism. The THESEE Study Group. Tinzaparine ou Heparine Standard: Evaluations dans l'Embolie Pulmonaire. Subcutaneous low-molecular-weight heparin compared with continuous intravenous unfractionated heparin in the treatment of proximal deep vein thrombosis. A comparison of low-molecular-weight heparin administered primarily at home with unfractionated heparin administered in the hospital for proximal deep-vein thrombosis. Subcutaneous low molecular weight heparin versus subcutaneous unfractionated heparin in the treatment of deep vein thrombosis: a Polish multicenter trial. A multicentre comparison of once-daily subcutaneous dalteparin (low molecular weight heparin) and continuous intravenous heparin in the treatment of deep vein thrombosis. Subcutaneous adjusted-dose unfractionated heparin vs fixed-dose low-molecular-weight heparin in the initial treatment of venous thromboembolism. Low-molecular-weight heparin versus unfractionated heparin in the treatment of patients with acute pulmonary thromboembolism. A clinical trial of vena caval filters in the prevention of pulmonary embolism in patients with proximal deep-vein thrombosis. Prévention du Risque d'Embolie Pulmonaire par Interruption Cave Study Group. Comparison of low-molecular-weight heparin, administered primarily at home, with unfractionated heparin, administered in hospital, and subcutaneous heparin, administered at home for deep-vein thrombosis.
Low-molecular-weight heparin has a high bioavailability and a prolonged half-life in comparison with conventional unfractionated heparin. Limited data are available for low-molecular-weight heparin as compared with unfractionated heparin for the treatment of deep-vein thrombosis.
                In a multicenter, double-blind clinical trial, we compared fixed-dose subcutaneous low-molecular-weight heparin given once daily with adjusted-dose intravenous heparin given by continuous infusion for the initial treatment of patients with proximal-vein thrombosis, using objective documentation of clinical outcomes.
                Six of 213 patients who received low-molecular-weight heparin (2.8 percent) and 15 of 219 patients who received intravenous heparin (6.9 percent) had new episodes of venous thromboembolism (P = 0.07; 95 percent confidence interval for the difference, 0.02 percent to 8.1 percent). Major bleeding associated with initial therapy occurred in 1 patient receiving low-molecular-weight heparin (0.5 percent) and in 11 patients receiving intravenous heparin (5.0 percent), a reduction in risk of 91 percent (P = 0.006). This apparent protection against major bleeding was lost during long-term therapy. Minor hemorrhagic complications were infrequent. Ten patients receiving low-molecular-weight heparin (4.7 percent) died, as compared with 21 patients receiving intravenous heparin (9.6 percent), a risk reduction of 51 percent (P = 0.049).
                Low-molecular-weight heparin is at least as effective and as safe as classic intravenous heparin therapy under the conditions of this study and more convenient to administer. The simplified therapy provided by low-molecular-weight heparin may allow patients with uncomplicated proximal deep-vein thrombosis to be cared for in an outpatient setting. Body weight-adjusted subcutaneous low-molecular-weight heparin (LMWH) has been proven to be at least as effective and safe as dose-adjusted intravenous unfractionated heparin (UFH) for the treatment of patients with venous thromboembolism. However, body weight-adjusted dosage of low-molecular-weight heparin may be cumbersome and could lead possibly to incorrect dosing. Therefore a fixed LMWH dose, independent of body-weight, might rationalize initial treatment for venous thromboembolism.
                Patients with proven proximal deep-vein thrombosis were randomly assigned to fixed dose subcutaneous LMWH Certoparin (8,000 anti-factor Xa U b.i.d.; 265 patients) or to adjusted dose i.v. UFH (273 patients) for 12 days. Vitamin K antagonists were started between day 3 and 7 and continued for up to 6 months. The primary outcome measure was a 30 percent or greater improvement in the Marder Score, as revealed by repeated venography on day 12 (end of the initial treatment). The secondary composite outcome measure included death, recurrent venous thromboembolism and major bleeding and was assessed at day 12 and after 6 months by a blinded adjunction committee.
                The Marder score improved by 30% or more in 30.3% and 25.0% of patients assigned to LMWH (198 paired venograms) and UFH (192 paired venograms), respectively (2p = 0.26). At the end of the initial treatment, the composite outcome was observed in 4 of the 265 patients (1.5%) randomized to LMWH, as compared with 14 of the 273 patients (5.1%) randomized to UFH (2p = 0.03). At 6 months these figures were 6.8% and 12.8%, respectively (risk reduction 0.53, confidence interval 0.31-0.90, 2p = 0.02).
                Fixed dose subcutaneous LMWH certoparin is at least as efficacious as UFH in resolving proximal vein thrombosis. Subcutaneous body weight-adjusted low molecular weight heparin (LMWH) has been proven as effective and safe as intravenous aPTT-adjusted unfractionated heparin (UFH) for the treatment of patients with acute deep venous thrombosis (DVT). In this study we evaluate the efficacy of the initial treatment of proximal DVT with a fixed-dose, body weight-independent application of the LMWH Certoparin with a six month follow-up. In a prospective, multicentre, randomized, active-controlled study 1220 patients with objectively diagnosed proximal DVT were randomly assigned to subcutaneous 8000 U anti-factor Xa of Certoparin twice daily for 10 to 14 days or intravenous aPTT-adjusted UFH for 5 to 8 days. Both regimen were followed by oral anticoagulation for 6 months. The primary end point was the rate of symptomatic and objectively confirmed thromboembolic events within 6 months. The aim of the study was to demonstrate the non-inferiority of the Certoparin regimen as compared to UFH. The per-protocol analysis revealed 22 (3.8%) thromboembolic events in the Certoparin group and 24 (4.3%) in patients assigned to UFH within 6 months, thereby proving the non-inferiority (p<0.01), confirmed by intent-to-treat analysis (p<0.001). Major bleeding occurred in 6 and 7 patients started on Certoparin or UFH during the treatment period. Thromboembolic events were equally distributed in body weight categories with < 50, 50-80 and >80 kg as followed: 0, 3.6% and 4.1% of patients for the Certoparin group and 0, 4.6% and 4.2% of patients for the UFH group. The same was true for major bleeding complications with 0, 2.9% and 1.5% for Certoparin and 0, 3.5% and 4.2% for UFH. Overall mortality was 1.9% in the Certoparin group and 2.7% in the UFH group. Fixed-dose body weight-independent subcutaneous LMWH Certoparin is at least as efficacious and safe as intravenous aPTT-adjusted UFH for the initial treatment of acute proximal DVT. This effect is maintained during a 6-months follow-up of treatment with oral anticoagulation. Low-molecular-weight heparin is known to be safe and effective for the initial treatment of patients with proximal deep-vein thrombosis. However, its application to pulmonary embolism or previous episodes of thromboembolism has not been studied.
                We randomly assigned 1021 patients with symptomatic venous thromboembolism to fixed-dose, subcutaneous low-molecular-weight heparin (reviparin sodium) or adjusted-dose, intravenous unfractionated heparin. Oral anticoagulant therapy with a coumarin derivative was started concomitantly and continued for 12 weeks. Approximately one third of the patients had associated pulmonary embolism. The outcome events studied over the 12 weeks were symptomatic recurrent venous thromboembolism, major bleeding, and death. We sought to determine whether low-molecular-weight heparin is at least equivalent to unfractionated heparin in patients with venous thromboembolism.
                Twenty-seven of the 510 patients assigned to low-molecular-weight heparin (5.3 percent) had recurrent thromboembolic events, as compared with 25 of the 511 patients assigned to unfractionated heparin (4.9 percent). The difference of 0.4 percentage point indicates that the two therapies have equivalent value according to our predetermined definition of equivalence. Sixteen patients assigned to low-molecular-weight heparin (3.1 percent) and 12 patients assigned to unfractionated heparin (2.3 percent) had episodes of major bleeding (P= 0.63), and the mortality rates in the two groups were 7.1 percent and 7.6 percent, respectively (P=0.89).
                Fixed-dose, subcutaneous low-molecular-weight heparin is as effective and safe as adjusted-dose, intravenous unfractionated heparin for the initial management of venous thromboembolism, regardless of whether the patient has pulmonary embolism or a history of venous thromboembolism. Two hundred and four consecutive patients with venographically confirmed deep vein thrombosis (DVT) were randomised either to a low molecular weight heparin, Fragmin, administered subcutaneously (s.c.) once daily as a fixed dose of 200 IU anti-factor Xa/kg or to continuous intravenous infusion of unfractionated heparin (UFH). The UFH dose was adjusted to maintain the activated partial thromboplastin time between 1.5 and 3.0 times the upper limit of the reference value at each centre. Fragmin or UFH was given for a minimum of 5 days until anticoagulation with warfarin, given from day 1, was established (i.e. an Internation Normalised Ratio, of 2.0-3.0). A second venogram was obtained after Fragmin or UFH treatment. There were no significant differences in the change in mean Marder score before and after treatment between the two treatment groups, irrespective of thrombus localisation. No major bleeding events, symptomatic pulmonary embolism, symptomatic thrombosis progression or death occurred during hospitalisation. Eight documented venous thromboembolic events occurred before the follow-up visit 6 months after randomisation: 5 in patients treated with Fragmin and 3 in those treated with UFH. Six of these events occurred after cessation of warfarin treatment. In conclusion Fragmin given s.c. once daily in a fixed dose adjusted for body weight, is no less effective or safe than a continuous infusion of UFH in the initial treatment of acute DVT. Sixty-eight patients with acute deep vein thrombosis were allocated at random to two treatment groups. One group (n = 33) received a fixed dose of 750 anti-Xa units of a low molecular weight heparin (CY 222 Choay Institute); the other group (n = 35) received standard heparin in doses of 500 IU/kg/24 h. Both treatments were given for 10 days in two daily subcutaneous injections. A second phlebography was performed on the last day of treatment. No haemorrhagic complication was observed in the group treated with CY 222, as opposed to three cases of haemorrhage in the group treated with standard heparin. The initial phlebographic score and the location of deep vein thrombotic lesions were the same in both groups. Angiographic improvement, with more than 30% thrombolysis, was obtained at the end of treatment in 64% of patients in the CY 222 group and in 65% of patients in the standard heparin group (NS). In 2 patients treated with standard heparin the second phlebography showed extension of the thrombosis. The initial score remained unchanged in 1/3 of patients in both groups. The activated partial thromboplastin time was prolonged (2 or 3 fold the normal value) in the standard heparin group and unchanged in the CY 222 group. Anti-Xa activity was significantly higher in the CY 222 group than in the standard heparin group. It is concluded that CY 222 and standard heparin were equally effective in patients with deep vein thrombosis. However, haemorrhagic complications were more frequent with standard heparin that with CY 222. The main objective of the study presented was to test if thrombus regression can be improved by treatment with an intravenously or subcutaneously administered low molecular weight heparin (LMWH). Patients with acute deep vein thrombosis were randomly assigned to receive either intravenous UFH (131 patients), intravenous (i.v.) LMWH (128 patients), or 8000 IU of the same LMWH bid subcutaneously (s.c.) (128 patients). All patients were treated with heparin for 14 to 16 days. Vitamin-K-antagonist prophylaxis was started between Day 12 and Day 14 after enrollment into the study.
                Phlebographies and perfusion/ventilation lung scans were performed at baseline and on Days 12 to 16. Primary endpoint of the study was a reduction of the phlebographic Marder score. Secondary endpoints were recurrent thrombosis and pulmonary embolism (PE), major and minor bleedings and the rate of PE at inclusion and at the end of the study assessed by ventilation/perfusion scans.
                The Marder score improved by at least 30% in 32.4% (95% CI: 22.6 ... 42.2) of the patients receiving UFH, in 34.0% (95% CI: 24.9 ... 44.0) receiving LMWH i.v. and in 42.6% (95% CI: 32.8 ... 52.8) treated with the low molecular weight heparin s.c. The difference between LMWH s.c. and UFH was 10.2% (95% CI: -3.7% ... +24.5%) (p = 0.11). PE with clinical signs confirmed by objective methods occurred in three patients of the UFH group, one of whom died and was not observed in patients of the i.v. or s.c. LMWH-groups. During the first 15 days no patient receiving UFH or i.v. LMWH, and one patient on s.c. LMWH had a recurrent thrombosis. Major bleedings were observed in four patients receiving i.v. UFH compared to nine patients on i.v. LMWH (one of these patients died) and one patient on s.c. LMWH. Perfusion ventilation lung scans were obtained from 287 patients at baseline and from 246 patients on Days 12-16. PE, defined according to PIOPED-criteria as intermediate or high probability scans, was observed in 38.0% of the patients entering the study and in 18.3% on Days 12 to 16. New asymptomatic PE occurred less frequently in the groups on LMWH (7.1%, 7.5%, respectively) than in the UFH-group (12.6%) (not significant).
                S.c. treatment with a LMWH (certoparin) (b.i.d.) is at least as effective as UFH i.v. The hypothesis of increased efficacy of subcutaneous LMWH in resolving venous thrombi will have to be confirmed by an independent study comparing s.c. LMWH with UFH. The i.v. continuous infusion of the LMWH for 12 to 16 days does not result in a higher venous re-opening rate than intravenous standard heparin. Low-molecular-weight heparins are frequently used to treat venous thromboembolism, but optimal dosing regimens and clinical outcomes need further definition.
                In this multicenter, open-label study with blinded adjudication of end points, we randomly assigned patients with acute deep-vein thrombosis to one of three treatment regimens: intravenous administration of unfractionated heparin; subcutaneous administration of a low-molecular-weight heparin, reviparin, twice a day for one week; or subcutaneous administration of reviparin once a day for four weeks. The primary end point was evidence of regression of the thrombus on venography on day 21; secondary end points were recurrent venous thromboembolism, major bleeding within 90 days after enrollment, and death.
                Of the patients receiving unfractionated heparin, 40.2 percent (129 of 321) had thrombus regression, as compared with 53.4 percent (175 of 328) of patients receiving reviparin twice daily and 53.5 percent (167 of 312) of the patients receiving reviparin once daily. With regard to thrombus regression, reviparin administered twice daily was significantly more effective than unfractionated heparin (relative likelihood of thrombus regression, 1.28; 97.5 percent confidence interval, 1.08 to 1.52), as was reviparin administered once daily (relative likelihood, 1.29; 97.5 percent confidence interval, 1.08 to 1.53). Mortality and the frequency of episodes of major bleeding were similar in the three groups.
                In acute deep-vein thrombosis, reviparin regimens are more effective than unfractionated heparin in reducing the size of the thrombus. Reviparin is also more effective than unfractionated heparin for the prevention of recurrent thromboembolism and equally safe. Ardeparin sodium has recently received approval by the Food and Drug Administration for prophylaxis against venous thromboembolism in patients undergoing elective total knee replacement. However, this low-molecular-weight heparin has not been previously evaluated in a randomized controlled trial for treatment of established acute deep venous thrombosis.
                The study included patients with ultrasound-documented acute symptomatic deep venous thrombosis of the legs. They had to be deemed appropriate for discharge home to receive subcutaneous low-molecular-weight heparin. Patients were randomized to receive ardeparin with a 2-day hospitalization or unfractionated heparin sodium with a 5-day hospitalization. Both groups received warfarin sodium. Follow-up ultrasound examinations were undertaken at 6 weeks.
                Of the 80 patients enrolled, 75 had follow-up ultrasonography. Evaluation of baseline vs 6-week venous scans demonstrated that, overall, 31 of the 39 ardeparin-treated patients improved, compared with 21 of the 36 patients assigned to receive unfractionated heparin (P=.05). The 95% confidence interval for the difference in improvement was 0.6% to 42% in favor of ardeparin. Median charges for ardeparin and unfractionated heparin were $2815 and $6500, respectively (P<.001). There were no differences in bleeding or patient satisfaction between the 2 groups.
                The results of this small preliminary trial suggest that ardeparin can be administered effectively and safely to selected patients with acute deep venous thrombosis and that, with proper nursing and home services, it can help decrease the duration of hospitalization. The aim of the study was to compare the efficacy and safety of once-daily subcutaneous injection of dalteparin, a low molecular weight heparin, with that of intravenous unfractionated heparin in the treatment of deep venous thrombosis (DVT). Patients were included if they had deep venous thrombosis distal to inguinal ligament and were randomised either before, if it was considered necessary, or after phlebographic verification of the diagnosis. There was no pre-inclusion treatment with unfractionated heparin. One hundred and twenty patients received dalteparin, administered subcutaneously once-daily at a fixed dose of 200 IU anti-factor Xa/kg, and 133 patients received a continuous intravenous infusion of unfractionated heparin (UFH). Oral anticoagulation was started on the first or second day, and initial treatment with dalteparin or UFH discontinued when the prothrombin time was in the therapeutic range (2 < INR < 3) on two consecutive days. Control phlebograms were taken within 4 days, thereafter. There were no significant differences between the two initial treatment groups in improvements in Marder score. Two major bleeding events occurred in the UFH group versus none in the dalteparin group. One patient in each group experienced clinically significant pulmonary embolism. During a mean follow-up period of 6.9 +/- 1.5 months, recurrent DVT occurred in four patients in the dalteparin group and in two of the UFH group. These results confirm those of a previous study on dalteparin in the initial treatment of DVT, and suggest that dalteparin administered once-daily at a fixed dose of 200 UI/kg is as effective and well-tolerated as UFH in patients with DVT below the inguinal ligament. The present study also demonstrates that dalteparin can be started as soon as the diagnosis of DVT is suspected and without pre-treatment with UFH. Given that the administration of once-daily subcutaneous injections needs not require a patient to be hospitalised, studies to investigate the possibility of using dalteparin for the initial treatment of DVT in the outpatient setting are warranted. Low-molecular-weight heparins administered subcutaneously once or twice daily have been reported to be as safe and efficacious as intravenous unfractionated heparin in the treatment of acute venous thromboembolic disease.
                To determine whether subcutaneous enoxaparin administered once or twice daily is as effective as continuously infused unfractionated heparin in acute symptomatic venous thromboembolic disease.
                Randomized, controlled, partially blinded equivalence trial.
                74 hospitals in 16 countries.
                900 patients with symptomatic lower-extremity deep venous thrombosis, including 287 (32%) with confirmed pulmonary embolism.
                Initial therapy with dose-adjusted intravenous unfractionated heparin compared with subcutaneous enoxaparin at fixed dosages of 1.0 mg/kg of body weight twice daily or 1.5 mg/kg once daily. Long-term oral anticoagulation was started in all patients within 72 hours of randomization.
                Clinical end points assessed during a 3-month follow-up period.
                Equivalent efficacy was seen in the heparin group and both enoxaparin groups. Symptomatic venous thromboembolism recurred in 12 of 290 patients receiving unfractionated heparin (4.1%), 13 of 298 patients receiving once-daily enoxaparin (4.4%), and 9 of 312 patients receiving twice-daily enoxaparin (2.9%). Compared with unfractionated heparin, the treatment difference was 0.2% (95% CI, -3.04% to 3.49%) for once-daily enoxaparin and -1.2% (CI, -4.2% to 1.7%) for twice-daily enoxaparin. Incidence of major hemorrhage did not differ among the three treatment groups. Major hemorrhage occurred in 6 of 290 patients (2.1%) in the unfractionated heparin group, 5 of 298 patients (1.7%) in the once-daily enoxaparin group, and 4 of 312 patients (1.3%) in the twice-daily enoxaparin group.
                Subcutaneous enoxaparin once or twice daily is as effective and safe as dose-adjusted, continuously infused unfractionated heparin in the prevention of recurrent symptomatic venous thromboembolic disease. An intravenous course of standard (unfractionated) heparin with the dose adjusted to prolong the activated partial-thromboplastin time to a desired length is the standard initial in-hospital treatment for patients with deep-vein thrombosis, but fixed-dose subcutaneous low-molecular-weight heparin appears to be as effective and safe. Because the latter treatment can be given on an outpatient basis, we compared the two treatments in symptomatic outpatients with proximal-vein thrombosis but no signs of pulmonary embolism.
                We randomly assigned patients to adjusted-dose intravenous standard heparin administered in the hospital (198 patients) or fixed-dose subcutaneous low-molecular-weight heparin administered at home, when feasible (202 patients). We compared the treatments with respect to recurrent venous thromboembolism, major bleeding, quality of life, and costs.
                Seventeen of the 198 patients who received standard heparin (8.6 percent) and 14 of the 202 patients who received low-molecular-weight heparin (6.9 percent) had recurrent thromboembolism (difference, 1.7 percentage points; 95 percent confidence interval, -3.6 to 6.9). Major bleeding occurred in four patients assigned to standard heparin (2.0 percent) and one patient assigned to low-molecular-weight heparin (0.5 percent; difference, 1.5 percentage points; 95 percent confidence interval, -0.7 to 2.7). Quality of life improved in both groups. Physical activity and social functioning were better in the patients assigned to low-molecular-weight heparin. Among the patients in that group, 35 percent were never admitted to the hospital at all, and 40 percent were discharged early. This treatment was associated with a mean reduction in hospital days of 67 percent, ranging from 29 percent to 86 percent in the various study centers.
                In patients with proximal-vein thrombosis, treatment with low-molecular-weight heparin at home is feasible, effective, and safe. Low-molecular-weight heparin appears to be at least as effective and safe as standard, unfractionated heparin for the treatment of deep-vein thrombosis, but only limited data are available on the use of low-molecular-weight heparin to treat acute symptomatic pulmonary embolism.
                We randomly assigned 612 patients with symptomatic pulmonary embolism who did not require thrombolytic therapy or embolectomy to either subcutaneous low-molecular-weight heparin (tinzaparin) given once daily in a fixed dose or adjusted-dose, intravenous unfractionated heparin. Oral anticoagulant therapy was begun between the first and the third day and was given for at least three months. We compared the treatments at day 8 and day 90 with respect to a combined end point of recurrent thromboembolism, major bleeding, and death.
                In the first eight days of treatment, 9 of 308 patients assigned to receive unfractionated heparin (2.9 percent) reached at least one of the end points, as compared,with 9 of 304 patients assigned to low-molecular-weight heparin (3.0 percent; absolute difference, 0.1 percentage point; 95 percent confidence interval, -2.7 to 2.6). By day 90, 22 patients assigned to unfractionated heparin (7.1 percent) and 18 patients assigned to low-molecular-weight heparin (5.9 percent) had reached at least one end point (P=0.54; absolute difference, 1.2 percentage points; 95 percent confidence interval, -2.7 to 5.1). The risk of major bleeding was similar in the two treatment groups throughout the study.
                Under the conditions of this study, initial subcutaneous therapy with the low-molecular-weight heparin tinzaparin appeared to be as effective and safe as intravenous unfractionated heparin in patients with acute pulmonary embolism. A low-molecular-weight heparin, enoxaparin sodium, has been shown to be effective and safe in preventing deep vein thrombosis both in general surgery and in high-risk orthopedic surgery. We conducted a controlled, randomized trial with enoxaparin in the treatment of established deep vein thrombosis.
                In a multicenter trial, we compared fixed-dose subcutaneous enoxaparin, given twice daily, with adjusted-dose intravenous unfractionated heparin (UFH) given by continuous intravenous infusion for the initial 10 days of treatment of patients with proximal vein thrombosis. The primary efficacy outcome was the change of the size of the thrombus assessed by repeated venograms between day 0 and day 10. The primary analysis of safety was based on the incidence of major bleeding during 10 days of treatment.
                There were 67 patients in each group. Venographic assessment of clot size evolution between day 0 and day 10 showed a statistically significant superiority (P < .002) of enoxaparin over the reference treatment with UFH. Moreover, the incidence of overall recurrent thromboembolic events during 10 days of treatment was significantly higher (P < .002) in the UFH group (seven of 67) than in the enoxaparin group (one of 67). There were no serious bleeding complications in either group.
                Enoxaparin is at least as effective and safe as UFH under the conditions of this study. Moreover, it is more comfortable for patients and less time-consuming for nurses and laboratories. Thus, our study confirmed, with the use of enoxaparin, other observations that low-molecular-weight heparin provides a real therapeutic advance in the treatment of deep vein thrombosis. Patients with acute proximal deep-vein thrombosis are usually treated first in the hospital with intravenous standard (unfractionated) heparin. However, the longer plasma half-life, better bioavailability after subcutaneous administration, and more predictable anticoagulant response of low-molecular-weight heparins make them attractive for possible home use. We compared these two approaches.
                Patients with acute proximal deep-vein thrombosis were randomly assigned to receive either intravenous standard heparin in the hospital (253 patients) or low-molecular-weight heparin (1 mg of enoxaparin per kilogram of body weight subcutaneously twice daily) administered primarily at home (247 patients). The study design allowed outpatients taking low-molecular-weight heparin to go home immediately and hospitalized patients taking low-molecular-weight heparin to be discharged early. All the patients received warfarin starting on the second day.
                Thirteen of the 247 patients receiving low-molecular-weight heparin (5.3 percent) had recurrent thromboembolism, as compared with 17 of the 253 patients receiving standard heparin (6.7 percent; P=0.57; absolute difference, 1.4 percentage points; 95 percent confidence interval, -3.0 to 5.7). Five patients receiving low-molecular-weight heparin had major bleeding, as compared with three patients receiving standard heparin. After randomization, the patients who received low-molecular-weight heparin spent a mean of 1.1 days in the hospital, as compared with 6.5 days for the standard-heparin group; 120 patients in the low-molecular-weight- heparin group did not need to be hospitalized at all.
                Low-molecular-weight heparin can be used safely and effectively to treat patients with proximal deep-vein thrombosis at home. In a prospective multicenter trial, 149 consecutive patients with phlebographically proven proximal and/or distal deep vein thrombosis of the leg were randomly allocated to receive subcutaneously for 10 days either low molecular weight heparin CY 216 (Fraxiparine) in a fixed dose or unfractionated heparin (UFH) in doses adjusted according to the activated partial thromboplastin time. Pre- and post-treatment phlebograms were assessed blindly using the Arnesen's score system in 134 patients available for analysis of the treatment efficacy. The mean phlebographic score after 10 days of treatment was significantly decreased in both groups (p less than 0.001) in comparison with the baseline score but the difference in score changes between the two groups was not statistically significant. There was an improvement in 45/68 patients (66%) in the Fraxiparine group and in 32/66 patients (48%) in the UFH group, and an increase in the thrombus size in 10/68 (15%) and 12/66 (18%), respectively. One symptomatic non-fatal pulmonary embolism and one major bleeding episode were observed in the UFH group. During a follow-up period of 3 months, two rethromboses had occurred in the UFH group and none in the Fraxiparine group. It is concluded that subcutaneous fixed dose Fraxiparine is safe and at least as effective as subcutaneous adjusted UFH in the treatment of deep vein thrombosis. To compare the efficacy and safety of the low molecular weight heparin (LMWH) dalteparin with unfractionated heparin (UFH) in the acute treatment of DVT patients who had not previously received UFH.
                An open randomized multicentre trial with blinded analysis of venograms.
                Seven hospitals in Sweden, Finland and the USA.
                A total of 330 patients, of 20 years or older, with suspected DVT, verified using venography.
                Fixed-dose dalteparin (200 IU kg-1) given as a once-daily subcutaneous injection, or aPTT adjusted i.v. UFH infusion for 6 to 10 days.
                Change in Marder score in patients with confirmed DVT and two evaluable venograms; PE, bleeding events and follow-up.
                Marder scores improved in 51% (95% CI 42-60%) of 92 patients treated with dalteparin and in 62% (95% CI 53-70%) of 98 patients treated with UFH (P = 0.152). One dalteparin-treated patient had a PE confirmed by V/Q scan; another had progressive thrombosis with swelling in the affected limb. Bleeding complications occurred in six patients in each group. One patient treated with dalteparin and five treated with UFH died during the 6-month follow-up period as a result of underlying malignancy or heart disease. The 6-month recurrence rate was low with both treatments (dalteparin, 3/97; UFH, 2/103).
                Fixed-dose subcutaneous dalteparin given once daily from the start of treatment is of equivalent efficacy and safety to conventional UFH therapy in the routine management of DVT. Few reports have addressed the value of unfractionated heparin (UFH) or low-molecular-weight heparin in treating the full spectrum of patients with venous thromboembolism (VTE), including recurrent VTE and pulmonary embolism.
                In an open, multicenter clinical trial, 720 consecutive patients with acute symptomatic VTE, including 119 noncritically ill patients (16.5%) with pulmonary embolism and 102 (14.2%) with recurrent VTE, were randomly assigned to treatment with subcutaneous UFH with dose adjusted by activated partial thromboplastin time by means of a weight-based algorithm (preceded by an intravenous loading dose), or fixed-dose (adjusted only to body weight) subcutaneous nadroparin calcium. Oral anticoagulant therapy was started concomitantly and continued for at least 3 months. We recorded the incidence of major bleeding during the initial heparin treatment and that of recurrent VTE and death during 3 months of follow-up.
                Fifteen (4.2%) of the 360 patients assigned to UFH had recurrent thromboembolic events, as compared with 14 (3.9%) of the 360 patients assigned to nadroparin (absolute difference between rates, 0.3%; 95% confidence interval, -2.5% to 3.1%). Four patients assigned to UFH (1.1%) and 3 patients assigned to nadroparin (0.8%) had episodes of major bleeding (absolute difference between rates, 0.3%; 95% confidence interval, -1.2% to 1.7%). Overall mortality was 3.3% in each group.
                Subcutaneous UFH with dose adjusted by activated partial thromboplastin time by means of a weight-based algorithm is as effective and safe as fixed-dose nadroparin for the initial treatment of patients with VTE, including those with pulmonary embolism and recurrent VTE. Low-molecular-weight heparin (LMWH) appears to be as effective as unfractionated heparin (UFH) for both treatment and prophylaxis of deep vein thrombosis (DVT), but limited data are available for its use in acute pulmonary thromboembolism (PTE).
                To determine whether enoxaparin, a LMWH, was clinically as efficient and safe as UFH in patients with a diagnosis of acute PTE.
                After exclusion of those with massive forms, 59 patients with acute PTE were randomly assigned to either subcutaneous enoxaparin given twice daily (1 mg/kg/dose) or adjusted dose intravenous UFH. Oral anticoagulant treatment was begun on the second day and was given for at least 6 months. We compared the treatment regimens at day 8 and day 90 with respect to a combined end point of major bleeding, recurrent venous thromboembolism (VTE), and death.
                In the first 8 days of treatment, 1 of 30 patients assigned to receive UFH (3.3%) reached one of the end points (recurrence), as compared with none of 29 patients assigned to enoxaparin. Statistically this difference was not significant (p = 0.508). By day 90, 3 patients assigned to UFH (10%) had symptomatic recurrent VTE, as compared with 1 patient assigned to enoxaparin (3.4%). There was neither major bleeding nor death in the study groups. There was an absolute difference of 6.4 percentage points between the two treatment groups, but the difference was statistically not significant (p = 0.318).
                Initial subcutaneous treatment with enoxaparin appeared to be as effective and safe as UFH in acute PTE.
                Copyright 2002 S. Karger AG, Basel The efficacy and safety of vena caval filters in the prevention of pulmonary embolism in patients with proximal deep-vein thrombosis is still a matter of debate.
                Using a two-by-two factorial design, we randomly assigned 400 patients with proximal deep-vein thrombosis who were at risk for pulmonary embolism to receive a vena caval filter (200 patients) or no filter (200 patients), and to receive low-molecular-weight heparin (enoxaparin, 195 patients) or unfractionated heparin (205 patients). The rates of recurrent venous thromboembolism, death, and major bleeding were analyzed at day 12 and at two years.
                At day 12, two patients assigned to receive filters (1.1 percent), as compared with nine patients assigned to receive no filters (4.8 percent), had had symptomatic or asymptomatic pulmonary embolism (odds ratio, 0.22; 95 percent confidence interval, 0.05 to 0.90). At two years, 37 patients assigned to the filter group (20.8 percent), as compared with 21 patients assigned to the no-filter group (11.6 percent), had had recurrent deep-vein thrombosis (odds ratio, 1.87; 95 percent confidence interval, 1.10 to 3.20). There were no significant differences in mortality or the other outcomes. At day 12, three patients assigned to low-molecular-weight heparin (1.6 percent), as compared with eight patients assigned to unfractionated heparin (4.2 percent), had had symptomatic or asymptomatic pulmonary embolism (odds ratio, 0.38; 95 percent confidence interval, 0.10 to 1.38).
                In high-risk patients with proximal deep-vein thrombosis, the initial beneficial effect of vena caval filters for the prevention of pulmonary embolism was counterbalanced by an excess of recurrent deep-vein thrombosis, without any difference in mortality. Our data also confirmed that low-molecular-weight heparin was as effective and safe as unfractionated heparin for the prevention of pulmonary embolism. In this study, 294 patients with acute proximal DVT (deep venous thrombosis) were randomly assigned to receive intravenous standard heparin in the hospital (98 patients) or low-molecular-weight heparin (LMWH) (nadroparin 0.1 mL [equivalent to 100 AXa IU] per kg of body weight subcutaneously twice daily) administered primarily at home (outpatients) or alternatively in hospital (97 patients) or subcutaneous calcium heparin (SCHep) (99 patients, 0.5 mL bid) administered directly at home. The study design allowed outpatients taking LMWH heparin to go home immediately and hospitalized patients taking LMWH to be discharged early. Patients treated with standard heparin or LMWH received the oral anticoagulant starting on the second day, and heparin was discontinued when the therapeutic range (INR 2-3) had been reached. Anticoagulant treatment was maintained for 3 months. Patients treated with SCHep were injected twice daily for 3 months without oral anticoagulants. Patients were evaluated for inclusion and follow-up with color duplex scanning. Venography was not used. In case of suspected pulmonary embolism (PE) a ventilatory-perfusional lung scan was performed. Endpoints of the study were recurrent or extension of DVT, bleeding, the number of days spent in hospital, and costs of treatments. Of the 325 patients included, 294 completed the study. Dropouts totaled 31 (10.5%); six of the 325 included patients (1.8%) died from the related, neoplastic illness. Recurrence or extension of DVT was observed in 6.1% of patients in the LMWH group, in 6.2% in the standard heparin group, and in 7.1% in the SCHep group. Most recurrences (11/17) were in the first month in all groups. Bleedings were all minor, mostly during hospital stay. Hospital stay in patients treated with LMWH was 1.2+/-1.4 days in comparison with 5.4+/-1.2 in those treated with standard heparin. There was no hospital stay in the SCHep group. Average treatment costs in 3 months in the standard heparin group (US $2,760) were considered to be 100%; in comparison costs in the LMWH group was 28% of the standard heparin and 8% in the SCHep group. This study indicated that LMWH and SCHep can be used safely and effectively to treat patients with proximal DVT at home at a lower cost.
Fixed dose LMWH is more effective and safer than adjusted dose UFH for the initial treatment of VTE. Compared to UFH, LMWH significantly reduced the incidence of thrombotic complications, the occurrence of major haemorrhage during initial treatment and overall mortality at follow up.