Comparison of fixed-dose weight-adjusted unfractionated heparin and low-molecular-weight heparin for acute treatment of venous thromboembolism.
BACKGROUND
When unfractionated heparin is used to treat acute venous thromboembolism, it is usually administered by intravenous infusion with coagulation monitoring, which requires hospitalization. However, subcutaneous administration of fixed-dose, weight-adjusted, unfractionated heparin may be suitable for inpatient and outpatient treatment of venous thromboembolism.


OBJECTIVE
To determine if fixed-dose, weight-adjusted, subcutaneous unfractionated heparin is as effective and safe as low-molecular-weight heparin for treatment of venous thromboembolism.


METHODS
Randomized, open-label, adjudicator-blinded, noninferiority trial of 708 patients aged 18 years or older with acute venous thromboembolism from 6 university-affiliated clinical centers in Canada and New Zealand conducted from September 1998 through February 2004. Of the randomized patients, 11 were subsequently excluded from the analysis of efficacy and 8 from the analysis of safety.


METHODS
Unfractionated heparin was administered subcutaneously as an initial dose of 333 U/kg, followed by a fixed dose of 250 U/kg every 12 hours (n = 345). Low-molecular-weight heparin (dalteparin or enoxaparin) was administered subcutaneously at a dose of 100 IU/kg every 12 hours (n = 352). Both treatments could be administered out of hospital and both were overlapped with 3 months of warfarin therapy.


METHODS
Recurrent venous thromboembolism within 3 months and major bleeding within 10 days of randomization.


RESULTS
Recurrent venous thromboembolism occurred in 13 patients in the unfractionated heparin group (3.8%) compared with 12 patients in the low-molecular-weight heparin group (3.4%; absolute difference, 0.4%; 95% confidence interval, -2.6% to 3.3%). Major bleeding during the first 10 days of treatment occurred in 4 patients in the unfractionated heparin group (1.1%) compared with 5 patients in the low-molecular-weight heparin group (1.4%; absolute difference, -0.3%; 95% confidence interval, -2.3% to 1.7%). Treatment was administered entirely out of hospital in 72% of the unfractionated heparin group and 68% of the low-molecular-weight heparin group.


CONCLUSIONS
Fixed-dose subcutaneous unfractionated heparin is as effective and safe as low-molecular-weight heparin in patients with acute venous thromboembolism and is suitable for outpatient treatment.


BACKGROUND
clinicaltrials.gov Identifier: NCT00182403.
Kearon
Clive
C
McMaster University and the Henderson Research Centre, Hamilton, Ontario.
Ginsberg
Jeffrey S
JS
Julian
Jim A
JA
Douketis
James
J
Solymoss
Susan
S
Ockelford
Paul
P
Jackson
Sharon
S
Turpie
Alexander G
AG
MacKinnon
Betsy
B
Hirsh
Jack
J
Gent
Michael
M
D000368:Aged; D000553:Ambulatory Care; D000925:Anticoagulants / Q000008:administration & dosage*; D004334:Drug Administration Schedule; D005260:Female; D006493:Heparin / Q000008:administration & dosage*; D006495:Heparin, Low-Molecular-Weight / Q000008:administration & dosage*; D006801:Humans; D007279:Injections, Subcutaneous; D008297:Male; D008875:Middle Aged; D010314:Partial Thromboplastin Time; D011655:Pulmonary Embolism / Q000188:drug therapy*; D020246:Venous Thrombosis / Q000188:drug therapy*
D000925:Anticoagulants; D006495:Heparin, Low-Molecular-Weight; D006493:Heparin