Background: Treatment of VTE with UFH is usually by intravenous (iv) infusion with adjustment of dose in response to the activated partial thromboplastin time (APTT). However, (1) there is no evidence that adjusting UFH in response to APTT results reduces recurrent VTE or bleeding if patients are receiving an appropriate dose of UFH, and (2) sc UFH might be preferable to iv UFH. We hypothesized that UFH is as effective and safe as LMWH when each is administered sc in weight-adjusted, fixed-doses.
Methods: We performed a multicentre, randomized, open-label, trial that compared fixed-dose UFH (first dose 333 u/kg sc, then 250 u/kg sc twice-daily) with fixed-dose LMWH (100 u/kg sc twice-daily) for initial treatment of acute VTE. Patients were followed for 3 months during which they received warfarin (target INR 2.0–3.0). Outcomes were adjudicated by a blinded committee.
Results: 703 patients who presented with acute DVT (81%) or PE (19%) were enrolled and received study drug (68% entirely as outpatients). Of the 352 LMWH patients, 74% received dalteparin and 26% received enoxaparin. Recurrent VTE occurred in 13 (3.8%) UFH and 12 (3.4%) LMWH patients in the 3 months (difference of 0.3%; 95% CI, −2.6 to 3.3%). Major bleeding occurred in 4 (1.1%) UFH and 5 (1.4%) LMWH patients in the first 10 days (difference of −0.3%; 95% CI, −2.3 to 1.7%), and a total of 6 (1.7%) UFH and 12 (3.4%) LMWH patients at 3 months. 18 (5.2%) UFH and 22 (6.3%) LMWH patients died.
Conclusion: Fixed-dose sc UFH is as effective and as safe as fixed-dose sc LMWH for treatment of acute VTE. Our findings: (1) support the use of fixed-dose sc UFH as a convenient and inexpensive alternative to LMWH; and (2) question the need for APTT monitoring of UFH therapy.