Subcutaneous (beneath the skin) injection of the original and less expensive form of the anticoagulant medication heparin is as effective and safe as subcutaneous administration of the newer and more expensive low-molecular-weight heparin for treatment of venous thromboembolism (blood clots in the deep veins of the legs or in the lungs), according to a study in the August 23-30 issue of JAMA.
Heparin is used to treat thromboembolism, formation of a blood clot in a blood vessel. When unfractionated (regular) heparin is used in the treatment, it is usually administered intravenously with coagulation monitoring, which requires hospitalization. The standard approach includes ongoing dose adjustment in response to measurements of the APTT, a test that measures how well and fast the blood clots, and is used to determine the most effective dosage, according to background information in the article. Low-molecular-weight heparin administered by subcutaneous (under the skin) injection in fixed weight-adjusted doses is gradually replacing unfractionated heparin, according to background information in the article.
Clive Kearon, M.B., Ph.D., of McMaster University and the Henderson Research Centre, Hamilton, Ontario, and colleagues conducted a randomized trial to determine if fixed-dose subcutaneous unfractionated heparin is as effective and safe as low-molecular-weight heparin for treatment of venous thromboembolism. The study was conducted from September 1998 through February 2004 at six university-affiliated clinical centers in Canada and New Zealand. About 70 percent of both groups were treated as outpatients. All patients received three months of warfarin (an anticoagulant drug) therapy. Patients received either unfractionated or low-molecular-weight heparin administered subcutaneously.
Recurrent thromboembolism occurred in 3.8 percent of 345 patients in the unfractionated heparin group and in 3.4 percent of 352 patients in the low-molecular weight heparin group. The rate of major bleeding was comparable in the two groups.
The authors estimate that drug costs for a six-day course of treatment with low-molecular-weight heparin would be $712, while unfractionated heparin would cost $37 - assuming both drugs are administered in the regimens used in the study. "Because unfractionated heparin costs less than low-molecular-weight heparin, the unfractionated heparin regimen is attractive for clinical practice," they write.
"We conclude that fixed-dose subcutaneous unfractionated heparin is as effective and safe as low-molecular-weight heparin for initial treatment of patients with venous thromboembolism and is suitable for treatment at home," they write. "In addition, the results of this study question the value of APTT monitoring in patients who are treated with currently recommended doses of unfractionated heparin." (JAMA. 2006;296:935-942. Available pre-embargo to the media at www.jamamedia.org.)
This study was supported by the Heart and Stroke Foundation of Ontario. Dr. Kearon and co-author James Douketis, M.D., were supported by the Heart and Stroke Foundation of Canada. Co-author Jeffrey S. Ginsberg, M.D., was supported by the Heart and Stroke Foundation of Ontario. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.
Financial disclosures - none reported.
Issues of Efficiency and Cost
In an accompanying editorial, Jeffrey L. Carson, M.D., of UMDNJ-Robert Wood Johnson Medical School, New Brunswick, N.J., writes that the question physicians must now answer is whether the evidence in the trial conducted by Kearon and colleagues is strong enough to change practice.
"Since the study by Kearon et al is the first trial to demonstrate that monitoring of APTT is not required, the results must be replicated using an adequately powered, double-blind trial design (in which neither physicians or patients know which anticoagulant the patient is receiving) before this approach can be adopted widely in clinical practice," he writes.
"If the patient can be observed very closely, this treatment regimen might be used very cautiously in carefully selected patients who prefer outpatient treatment of venous thromboembolism and cannot afford the expense of low-molecular-weight heparin," he continues.
"However, more than one study that demonstrates efficacy of this new treatment regimen is necessary before changing the management strategy for this potentially lethal disease," he concludes. (JAMA. 2006;296:991-993. Available pre-embargo to the media at www.jamamedia.org.)