Subcutaneous treatment of deep venous thrombosis with low molecular weight heparin. A dose finding study with LMWH-Novo. Frequency of pulmonary embolism in patients who have iliofemoral deep vein thrombosis and are treated with once- or twice-daily low-molecular-weight heparin. Subcutaneous enoxaparin once or twice daily compared with intravenous unfractionated heparin for treatment of venous thromboembolic disease. Comparison of a once daily with a twice daily subcutaneous low molecular weight heparin regimen in the treatment of deep vein thrombosis. FRAXODI group.
Treatment of deep venous thrombosis with low molecular weight heparin (LMWH-Novo, Logiparin) was carried out with two different doses of Logiparin, 75 XaI U/kg b.w. twice daily and 150 XaI U/kg b.w. once daily subcutaneously for 5 days. Simultaneously warfarin was given from the first day of heparin treatment. Mean age of the twenty patients was 65 years and one third was females. No serious side effects, hematomas, pulmonary emboli or signs of recurrent thrombosis occurred during treatment with either dose regime. Venografic assessment with Marder scoring one week after initiation of Logiparin treatment showed a slight not significant improvement apparent in 40% of the patients. The activities of F-IIaI and F-XaI in the blood plasma were found to increase after injection of Logiparin. These two parameters seem to be the most suitable for monitoring the effect during treatment. For future studies on the therapeutic effect of Logiparin in deep venous thrombosis a single dose of 150 to 200 F-XaI activity per 24 hours seems to be most suitable. The purpose of this study was to compare the efficacy and safety of treating mobile iliofemoral patients with deep venous thrombosis (DVT) with subcutaneous low-molecular-weight heparin (dalteparin sodium) either 200 IU/kg once-daily (group 1) or 100 IU/kg twice-daily (group 2).
                Consecutive patients with suspected iliofemoral DVT diagnosed by duplex ultrasonography and verified by radionuclide venography were randomized to one of the two low-molecular-weight heparin (LMWH) regimens. Perfusion and when necessary ventilation scans were performed for diagnosis of pulmonary emboli (PE) in all patients immediately after admission and were repeated after approximately 10 days, whereupon oral anticoagulation was started unless contraindicated. Minimal and maximal anti-factor Xa activity was measured after 2 to 3 days of therapy. All patients were kept mobile with compression bandages. The primary end point was reduction in frequency of PE as assessed on the second lung scan.
                A total of 140 patients with confirmed DVT were randomized, 76 to group 1 and 64 to group 2. The two groups were comparable in their baseline clinical characteristics. In the initial lung scans 36 (47.4%) patients in group 1 and 29 (45.3%) patients in group 2 had objectively verified PE, but only 11 (14.5%) and 8 (12.5%) patients, respectively, had symptoms. After dalteparin treatment PE disappeared in two patients in group 1, but in two other cases new PEs occurred, (NS). In group 2 a resolution of PEs was observed in eight patients, whereas only one new PE could be detected. This change reflects the efficacy of therapy as defined by resolution of existing PEs and by the occurrence of new PEs and is statistically significant according to McNemar's chi-square test with the exact binomial method pair procedure (p < 0.05). Symptomatic PE was reduced from 14.5% to 5.3% in group 1 (96% to CI for the difference, -1.5% to +17.3%) and from 12.5% to 1.6% in group 2 (95% CI for the difference 0.7% to 18%, p < 0.05). There was one single fatal PE, one serious and three minor bleeding episodes in group 1, and one minor bleeding episode in group 2 (95% CI for the difference: -3.6% to +8.1%).
                Treatment of ambulant iliofemoral patients with DVT with 100 IU/kg dalteparin twice-daily appears to be moe safe and effective than 200 IU/kg given once-daily. Bed rest is not necessary for treating mobile patients. 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. Clinical trials have been performed to compare with standard heparin a once or a twice daily regimen of low-molecular-weight heparin but no direct comparison has been done between these two low-molecular-weight heparin regimens in terms of efficacy and safety with a long-term clinical evaluation.
                Patients with proximal deep vein thrombosis, confirmed by venography were randomly assigned to either nadroparin (10,250 AXa IU/ml) twice daily or nadroparin (20,500 AXa IU/ml) once daily for at least 5 days. Regimens were adjusted to bodyweight. Oral anticoagulants were started on day 1 or 2 and continued for 3 months. Patients were followed up for 3 months. The composite outcome of venous thromboembolism and death possibly related to pulmonary embolism was the primary measure of efficacy. Major bleeding was the principal measure of safety. The study was designed to show equivalence between the two regimens.
                Recurrent thromboembolic events or death possibly related to pulmonary embolism were reported in 13 patients in the once daily group (4.1%) and in 24 patients of the twice daily group (7.2%): (absolute difference 3.1% in favor of the once daily regimen; 95% confidence interval -6.6%, +0.5%). Major bleeding episodes during nadroparin treatment occurred in 4 (1.3%) and 4 patients (1.2%) in the once and twice daily groups, respectively.
                A nadroparin regimen of one injection per day is at least as effective and safe as the same total daily dose divided over two injections for the treatment of acute deep vein thrombosis.
Once daily treatment with LMWH is as effective and safe as twice daily treatment with LMWH. However, the 95% confidence interval implies that there is a possibility that the risk of recurrent VTE might be higher when people are treated once daily. Hence, the decision to treat a person with a once daily regimen will depend on the evaluated balance between increased convenience and the potential for a lower efficacy.