Trials That Matter: Can Patients with Venous Thromboembolism Be Treated with Fixed-Dose Subcutaneous Unfractionated Heparin?

Unfractionated heparin (UFH) was the mainstay of initial treatment for acute venous thromboembolism (VTE) until low-molecular-weight heparin (LMWH) became available in the 1990s. Low-molecular-weight heparin was an attractive alternative to UFH because its excellent bioavailability allowed for convenient fixed, weight-based dosing. High-quality research subsequently confirmed the superior efficacy, safety, and cost-effectiveness of LMWH over UFH for treatment of deep venous thrombosis (1–4). As a result, most patients with this disorder who would require a minimum 5-day hospitalization if treated with UFH can now be treated with LMWH in an overnight stay or in the outpatient setting. Some evidence even supports the use of LMWH for less severe forms of pulmonary embolism (5).

Low-molecular-weight heparin saves the health system money, but it is nevertheless expensive, and a less costly but equally safe, effective, and convenient alternative would still be desirable. Fixed, weight-based doses of subcutaneous UFH might provide such an alternative. Fixed minidose subcutaneous UFH (5000 units 2 or 3 times daily) prevents VTE in hospitalized patients (6, 7), and older evidence hints that full-dose subcutaneous UFH might be as effective and safe as intravenous UFH for deep venous thrombosis treatment (8). However, until now, only 4 trials have directly compared full-dose subcutaneous UFH and LMWH for initial treatment of VTE (9–12). All were small, open-label trials that used an initial intravenous UFH bolus followed by adjustment of subcutaneous dosing based on activated partial thromboplastin time values. All of these studies concluded that LMWH and subcutaneous UFH were at least equivalent in efficacy; however, none was designed for formal noninferiority testing, and recurrent VTE events were few. Questions about the safety, efficacy, and cost advantage of subcutaneous UFH relative to LMWH for treatment of …