Comparison of Fixed-Dose Weight-Adjusted Unfractionated Heparin and Low-Molecular-Weight Heparin for Acute Treatment of Venous Thromboembolism
Kearon C, Ginsberg JS, Julian MA, et al
Summary and Viewpoint
Many patients now receive low-molecular-weight heparin (LMWH) instead of intravenous, continuous unfractionated heparin for the treatment of deep venous thrombosis (DVT). Beyond allowing outpatient management and avoiding the need for laboratory monitoring, LMWH may also provide clinical and economic benefits compared with intravenous unfractionated heparin. A meta-analysis of 8 clinical trials comparing the 2 types of heparin in the management of DVT found that LMWH reduced the risk for extension or recurrence of DVT by 38% compared with unfractionated heparin. The 2 types of heparin carried similar risks of major hemorrhage.
A prospective trial comparing treatment of DVT with LMWH and continuous intravenous unfractionated heparin found that the total clinical cost of care was approximately half in the LMWH group compared with the unfractionated heparin cohort. Moreover, this research demonstrated that subjects receiving LMWH had improved social functioning scores compared with participants receiving unfractionated heparin.
The research cited above compared continuous intravenous unfractionated heparin with LMWH, but some evidence exists that weight-adjusted unfractionated heparin delivered subcutaneously may provide similar outcomes compared with LMWH. In a study of 720 patients with DVT, subcutaneous unfractionated heparin adjusted for weight and activated partial thromboplastin time (APTT) was associated with a similar rate of recurrent thromboembolic events compared with the LMWH nadroparin. Rates of major bleeding were low overall and similar in the 2 treatment groups, and mortality rates were equal in both treatment groups.
The current study expands on this previous research with another comparison of low-molecular-weight heparin and subcutaneous unfractionated heparin for the treatment of DVT. In this study, the unfractionated heparin was adjusted for subjects' weights, but the researchers did not amend the dosage of unfractionated heparin on the basis of the APTT. Specifically, the doses of unfractionated heparin were 333 units/kg in the initial dose, then 250 units/kg twice daily, and the dose of low-molecular-weight heparin (dalteparin or enoxaparin) was 100 IU/kg twice daily.
The study focused on clinically relevant endpoints: Researchers followed patient symptoms and events as opposed to radiographic or laboratory outcomes. The study was also remarkable in that it included 134 subjects with pulmonary embolism. The mean duration of treatment with either heparin regimen was slightly less than 1 week, and outcomes, including mortality, were similar between the LMWH and unfractionated heparin groups.
A subgroup of participants receiving unfractionated heparin was assessed for APTT during therapy. Most of these patients had an APTT value considered greater than the recommended range of 60-80 seconds. However, no participant with an APTT over 85 seconds experienced an episode of major bleeding within 10 days of treatment. Moreover, no subject with an APTT less than 60 seconds experienced recurrent venous thromboembolism.
The current study makes APTT levels appear irrelevant in the management of DVT. The data are supported by a previous study examining heparin therapy for DVT. In this trial, combined data from 3 studies failed to demonstrate a superior result in terms of recurrence of DVT among subjects with therapeutic and subtherapeutic APTT levels.
The main limitation of the current study is its open-label design. However, the central adjudication committee which assessed all outcomes was blinded to participants' randomized treatment. While the researchers enrolled fewer patients than originally anticipated, the study was still adequately powered to detect a possible difference between the unfractionated heparin and LMWH.
The current study demonstrates the noninferiority of weight-adjusted subcutaneous unfractionated heparin when compared with LMWH for the treatment of DVT. It represents a potentially huge cost savings in the management of DVT. The authors performed a comparison of average medication costs for 6 days of treatment with subcutaneous unfractionated heparin or enoxaparin, and the total costs of therapy were $37 and $712, respectively. Physicians should note this cost difference, as insurance companies and administrators surely will. On the basis of the clinical data from the current study and the potential impact on medical economics, weight-adjusted subcutaneous unfractionated heparin may become the standard of care for DVT.
Medscape Family Medicine. 2006;8(2) © 2006 Medscape
Cite this: Unfractionated Heparin Adjusted for Weight Saves Money, but Is it as Good as LMWH? - Medscape - Oct 19, 2006.