Comparison of Fixed-Dose Weight-Adjusted Unfractionated Heparin and Low-Molecular-Weight Heparin for Acute Treatment of Venous Thromboembolism
- Clive Kearon, MB, PhD;
- Jeffrey S. Ginsberg, MD;
- Jim A. Julian, MMath;
- James Douketis, MD;
- Susan Solymoss, MD;
- Paul Ockelford, MD;
- Sharon Jackson, MD;
- Alexander G. Turpie, MB;
- Betsy MacKinnon, MSc;
- Jack Hirsh, MD;
- Michael Gent, DSc;
- for the Fixed-Dose Heparin (FIDO) Investigators
- Author Affiliations: McMaster University and the Henderson Research Centre, Hamilton, Ontario (Drs Kearon, Ginsberg, Douketis, Turpie, Hirsh, and Gent, Mr Julian, and Ms MacKinnon); McGill University, Montreal, Quebec (Dr Solymoss); and University of Auckland, Auckland, New Zealand (Drs Ockelford and Jackson).
- Corresponding Author: Clive Kearon, MB, PhD, Hamilton Health Sciences, Henderson Division, 711 Concession St, Hamilton, Ontario, Canada L8V 1C3 (kearonc{at}mcmaster.ca).
Abstract
Context 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.
Design, Setting, and Patients 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.
Interventions 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.
Main Outcome Measures 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.
Conclusion 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.
Trial Registration clinicaltrials.gov Identifier: NCT00182403
