Subcutaneous enoxaparin once or twice daily compared with intravenous unfractionated heparin for treatment of venous thromboembolic disease

Background: Low-molecular-weight heparins administered subcutaneously once or twice daily have been reported to be as safe and efficacious as intraven ous unfractionated heparin in the treatment of acute venous thromboembolic disease. Objective: To determine whether subcutaneous enoxaparin administered once o r twice daily is as effective as continuously infused unfractionated hepari n in acute symptomatic venous thromboembolic disease. Design: Randomized, controlled, partially blinded equivalence trial. Setting: 74 hospitals in 16 countries. Patients: 900 patients with symptomatic lower-extremity deep venous thrombo sis, including 287 (32%) with confirmed pulmonary embolism. Interventions: Initial therapy with dose-adjusted intravenous unfractionate d 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 antic oagulation was started in all patients within 72 hours of randomization. Me asurements: clinical end points assessed during a 3-month follow-up period. Results: Equivalent efficacy was seen in the heparin group and both enoxapa rin groups. Symptomatic venous thromboembolism recurred in 12 of 290 patien ts receiving unfractionated heparin (4.1%), 13 of 298 patients receiving on ce-daily enoxaparin (4.4%), and 9 of 312 patients receiving twice-daily eno xaparin (2.9%), Compared with unfractionated heparin, the treatment differe nce was 0.2% (95% Cl, -3.04% to 3.49%) for once-daily enoxaparin and -1.2% (Cl, -4.2% to 1.7%) for twice-daily enoxaparin. Incidence of major hemorrha ge did not differ among the three treatment groups. Major hemorrhage occurr ed in 6 of 290 patients (2.1%) in the unfractionated heparin group, 5 of 29 8 patients (1.7%) in the once-daily enoxaparin group, and 4 of 312 patients (1.3%) in the twice-daily enoxaparin group. Conclusions: Subcutaneous enoxaparin once or twice daily is as effective an d safe as dose-adjusted, continuously infused unfractionated heparin in the prevention of recurrent symptomatic venous thromboembolic disease.