Comparison of fixed-dose weight-adjusted unfractionated heparin and low-molecular-weight heparin for acute treatment of venous thromboembolism

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Conclusion: Low-molecular-weight heparin and fixed-dose subcutaneous unfractionated heparin are equally as effective for outpatient treatment of acute venous thromboembolism (VTE). Summary: The authors sought to determine if weight-adjusted, fixed-dose subcutaneous unfractionated heparin would be as effective and safe as low-molecular-weight heparin in the treatment of VTE. This was a randomized, adjudicated, blinded, open-labeled, noninferiority trial. There were 708 patients, all >18 years of age, and all had acute VTE. The study was conducted in six university-affiliated medical centers in New Zealand and Canada. The study ran from September 1998 through February 2004. Patients treated with weight-adjusted unfractionated heparin (n = 345) received an initial dose of 333 U/kg, followed by fixed doses of 250 U/kg every 12 hours. Patients treated with low-molecular-weight heparin (n = 352) received either dalteparin or enoxaparin. Low-molecular-weight heparin was administered subcutaneously at a dose of 100 IU/kg every 12 hours. Patients treated with either unfractionated or low-molecular-weight heparin could be treated as outpatients. Both forms of treatment overlapped with warfarin therapy for 3 months. The principal end point of the study was recurrent VTE or major bleeding within 10 days. A study drug was given for a mean of 6.6 days in the unfractionated heparin group and a mean of 7.1 days in the low-molecular-weight heparin group. There were 12 episodes (3.4%) of recurrent VTE in the low-molecular-weight heparin group and 13 episodes (3.8%) in the unfractionated heparin group. This was an absolute difference of 0.4% (95% confidence interval, −2.6% to 3.3%). Equal amounts of major bleeding occurred between the two groups, with major bleeding in the first 10 days of treatment in four patients (1.1%) in the unfractionated heparin group and in five patients (1.4%) in the low-molecular-weight heparin group (95% confidence interval, −2.3% to 1.7%). Treatment was administered outside of a hospital in 68% of the patients treated with low-molecular-weight heparin and 72% of the patients treated with weight-adjusted unfractionated heparin. In patients treated with unfractionated heparin, activated partial thromboplastin time (aPTT) was measured halfway between injections at a mean of 2.8 days after starting therapy. The aPTT values were <60 seconds in 39 patients, 60 to 85 seconds in 37, and >85 seconds in 121 patients. Levels of aPTT were not associated with recurrent VTE or major bleeding. Comment: The data suggest unfractionated heparin administered subcutaneously on a weight-based dosage regimen and low-molecular-weight heparin can provide equal protection against recurrent VTE in patients with acute VTE. The study has significant implications for all patients who are unable to afford the cost of low-molecular-weight heparin as an outpatient. Perhaps such patients can be treated at home with weight-based, fixed doses of unfractionated heparin? This will remove a potential barrier to outpatient treatment of acute VTE in patients who cannot afford the cost of low-molecular-weight heparin as an outpatient.