Once Daily Enoxaparin for Outpatient Treatment of Acute Deep Venous Thrombosis and/or Pulmonary Embolism

Background and Significance:

Low molecular weight heparin (LMWH) as a "bridge" to warfarin has become the standard of care for outpatient treatment of acute deep venous thrombosis (DVT). LMWH is also often prescribed as a "bridge" to warfarin for patients with acute pulmonary embolism (PE). In the United States, the FDA has approved enoxaparin only for twice daily dosing in outpatient treatment of acute DVT. The FDA has also approved enoxaparin for treatment of DVT with or without PE, but the FDA has not approved enoxaparin for the treatment of PE without DVT. The FDA has also not approved once daily enoxaparin for any DVT or PE treatment indication for outpatients.

Once daily dosing of enoxaparin in outpatients with DVT alone, DVT with PE, or PE without DVT will halve the number of required injections, facilitate outpatient treatment, and reduce health care costs. For example, visiting nurses will make one visit daily instead of two visits daily for those patients who are unable self-inject and for those patients who lack family or friends to inject LMWH.

Merli et al randomized 900 hospitalized venous thromboembolism (VTE) patients with acute DVT or PE to one of three treatment groups: 1) continuous infusion of unfractionated heparin (UFH), 2) once daily enoxaparin 1.5mg/kg, or 3) twice daily enoxaparin 1mg/kg. All study patients were inpatients. None were outpatients. They received once or twice daily enoxaparin or UFH for at least five days and were "bridged" to warfarin. Patients were followed for three months. Primary endpoints were recurrent DVT or PE. There were no significant differences in recurrent DVT or PE among the 3 treatment groups. There were 12 recurrent VTE events in the UFH group, 13 in the once daily enoxaparin group, and 9 in the twice daily enoxaparin group.

The frequency of major hemorrhage did not differ among the three treatment groups. Major hemorrhage occurred in 6 of 290 patients (2.1%) in the UFH 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.