Subcutaneous injection of fixed-dose unfractionated heparin is as effective and safe as subcutaneous use of low-molecular-weight heparin for treatment of venous thromboembolism, according to an article in the August 23 issue of the Journal of the American Medical Association.

Clive Kearon, MB, PhD, of McMaster University and the Henderson Research Centre, Hamilton, Ontario, and colleagues conducted a randomized trial to determine if fixed-dose subcutaneous unfractionated heparin was 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 therapy. Patients received either unfractionated or low-molecular-weight heparin 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 between 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," the authors wrote.

"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 wrote. "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."

In an accompanying editorial, Jeffrey L. Carson, MD, wrote 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 to accept treatment without monitoring by APTT testing.

Previously, unfractionated heparin was usually administered intravenously with coagulation monitoring, which requires hospitalization. Low-molecular-weight heparin administered by subcutaneous injection in fixed weight-adjusted doses is gradually replacing unfractionated heparin.

"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 wrote.

"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 continued.

"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 concluded.