This Article  • Full text  • PDF  • Send to a friend  • Save in My Folder  • Save to citation manager  • Permissions  Citing Articles  • Citation map  • Citing articles on HighWire  • Citing articles on Web of Science (121)  • Contact me when this article is cited  Related Content  • Related article  • Similar articles in this journal  Topic Collections  • Thrombolysis  • Venous Thromboembolism  • Cardiovascular System  • Surgery  • Orthopedic Surgery  • Randomized Controlled Trial  • Alert me on articles by topic  Social Bookmarking   What's this?

A Double-blind, Randomized Comparison

Russell D. Hull, MBBS, MSc; Graham F. Pineo, MD; Charles Francis, MD; David Bergqvist, MD, PhD; Carin Fellenius, CCRN, RNA; Karin Soderberg, CLT; Anna Holmqvist, BSc; Michael Mant, MB, ChB; Richard Dear, MBBS; Barry Baylis, MD; Andrew Mah, BSc; Rollin Brant, PhD; for the North American Fragmin Trial Investigators

Arch Intern Med. 2000;160:2208-2215.

Background  No randomized trials have directly evaluated the need for extended out-of-hospital thromboprophylaxis for patients who have hip arthroplasty in the United States or Canada. The uncertainty as to the need for extended prophylaxis in North American patients is complicated by early hospital discharge, resulting in a short thromboprophylaxis interval.

Methods  To resolve this uncertainty, we performed a randomized double-blind trial in 569 patients who underwent hip arthroplasty comparing the use of dalteparin sodium started immediately before surgery or early after surgery and extended out-of-hospital to an overall interval of 35 days with the use of warfarin sodium in-hospital and placebo out-of-hospital.

Results  For patients with interpretable venograms in the preoperative, postoperative, and combined dalteparin groups, new proximal vein thrombosis out-of-hospital was observed in 1.3%, 0.7% (P = .04), and 1.0% (P = .02) of patients, respectively, compared with 4.8% in the in-hospital warfarin/out-of-hospital placebo group. The respective overall cumulative frequencies of all deep vein thrombosis were 30 (17.2%) of 174 patients (P<.001), 38 (22.2%) of 171 (P = .003), and 68 (19.7%) of 345 (P<.001) in the dalteparin groups compared with 69 (36.7%) of 188 for the in-hospital warfarin/out-of-hospital placebo group. For proximal deep vein thrombosis, the respective frequencies were 5 (3.1%) of 162 (P = .02), 3 (2.0%) of 151 (P = .007), and 8 (2.6%) of 313 (P = .002) compared with 14 (9.2%) of 153. No major bleeding occurred during the extended prophylaxis interval.

Conclusions  Extended dalteparin prophylaxis resulted in significantly lower frequencies of deep vein thrombosis compared with in-hospital warfarin therapy. Despite in-hospital thromboprophylaxis, patients having hip arthroplasty in the United States and Canada remain at moderate risk out-of-hospital. The number needed to treat provides a public health focus; only 24 to 28 patients require extended prophylaxis to prevent 1 new out-of-hospital proximal vein thrombosis. Recent studies demonstrate that asymptomatic deep vein thrombi cause the postphlebitic syndrome; thus, extended out-of-hospital prophylaxis will lessen the burden to both the patient and society.

From the Thrombosis Research Unit, University of Calgary, Calgary, Alberta (Drs Hull, Pineo, and Brant and Mr Mah); University of Rochester Medical Center, Rochester, NY (Dr Francis); Uppsala University, Uppsala (Dr Bergqvist), Pharmacia & Upjohn, Stockholm (Mss Fellenius, Soderberg, and Holmqvist), Sweden; University of Alberta Hospital, Edmonton (Dr Mant); Peter Lougheed Center and Calgary General Hospital, Calgary (Dr Dear); and Foothills Medical Center, Calgary (Dr Baylis).

CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter     What's this?

RELATED ARTICLE

Low-Molecular-Weight Heparin Prophylaxis Using Dalteparin in Close Proximity to Surgery vs Warfarin in Hip Arthroplasty Patients: A Double-blind, Randomized Comparison
Russell D. Hull, Graham F. Pineo, Charles Francis, David Bergqvist, Carin Fellenius, Karin Soderberg, Anna Holmqvist, Michael Mant, Richard Dear, Barry Baylis, Andrew Mah, Rollin Brant, and for the North American Fragmin Trial Investigators
Arch Intern Med. 2000;160(14):2199-2207.
ABSTRACT | FULL TEXT  

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES

Venous Thromboembolic Disease After Total Hip and Knee Arthroplasty
Haas et al.
JBJS 2008;90:2764-2780.
FULL TEXT  

Prevention of Venous Thromboembolism: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition)
Geerts et al.
Chest 2008;133:381S-453S.
ABSTRACT | FULL TEXT  

Outpatient-Based Primary and Secondary Thromboprophylaxis With Low-Molecular-Weight Heparin
Spyropoulos
CLIN APPL THROMB HEMOST 2008;14:63-74.
ABSTRACT  

The Cost-Effectiveness of Extended-Duration Antithrombotic Prophylaxis After Total Hip Arthroplasty
Skedgel et al.
JBJS 2007;89:819-828.
ABSTRACT | FULL TEXT  

Optimal Duration of Prophylaxis for Venous Thromboembolism Following Total Hip Arthroplasty and Total Knee Arthroplasty
Friedman
J Am Acad Orthop Surg 2007;15:148-155.
ABSTRACT | FULL TEXT  

Assessment of a self-administration protocol for extended subcutaneous thromboprophylaxis in lower limb arthroplasty
Watts et al.
J Bone Joint Surg Br 2006;88-B:107-110.
ABSTRACT | FULL TEXT  

Prevention of Venous Thromboembolic Disease After Total Hip and Knee Arthroplasty
Lieberman and Hsu
JBJS 2005;87:2097-2112.
ABSTRACT | FULL TEXT  

Relationship between intraoperative transoesophageal echocardiography findings and perfusion lung scintigraphy results on first postoperative day
Moriyama et al.
Br J Anaesth 2005;94:607-612.
ABSTRACT | FULL TEXT  

Neuraxial Anesthesia and Low-Molecular-Weight Heparin Prophylaxis in Major Orthopedic Surgery in the Wake of the Latest American Society of Regional Anesthesia Guidelines
Rowlingson and Hanson
Anesth. Analg. 2005;100:1482-1488.
ABSTRACT | FULL TEXT  

Efficacy and Safety of Fixed Low-Dose Dalteparin in Preventing Venous Thromboembolism Among Obese or Elderly Hospitalized Patients: A Subgroup Analysis of the PREVENT Trial
Kucher et al.
Arch Intern Med 2005;165:341-345.
ABSTRACT | FULL TEXT  

Ximelagatran: An Oral Direct Thrombin Inhibitor
Dager et al.
The Annals of Pharmacotherapy 2004;38:1881-1897.
ABSTRACT | FULL TEXT  

Therapeutic Update on the Prevention and Treatment of Venous Thromboembolism
McGuire and Dobesh
Journal of Pharmacy Practice 2004;17:289-307.
ABSTRACT  

New Anticoagulant Drugs: The Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy
Weitz et al.
Chest 2004;126:265S-286S.
ABSTRACT | FULL TEXT  

Prevention of Venous Thromboembolism: The Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy
Geerts et al.
Chest 2004;126:338S-400S.
ABSTRACT | FULL TEXT  

Natural History of Venous Thromboembolism
Kearon
Circulation 2003;107:I-22-30.
ABSTRACT | FULL TEXT  

Duration of Prophylaxis Against Venous Thromboembolism With Fondaparinux After Hip Fracture Surgery: A Multicenter, Randomized, Placebo-Controlled, Double-blind Study
Eriksson and Lassen
Arch Intern Med 2003;163:1337-1342.
ABSTRACT | FULL TEXT  

Reduction of Out-of-Hospital Symptomatic Venous Thromboembolism by Extended Thromboprophylaxis With Low-Molecular-Weight Heparin Following Elective Hip Arthroplasty: A Systematic Review
O'Donnell et al.
Arch Intern Med 2003;163:1362-1366.
ABSTRACT | FULL TEXT  

Venous Thromboembolism Prevention with LMWHs in Medical and Orthopedic Surgery Patients
Deitelzweig et al.
The Annals of Pharmacotherapy 2003;37:402-411.
ABSTRACT | FULL TEXT  

Rationale and design of a clinical trial of a low-molecular-weight heparin in preventing clinically important venous thromboembolism in medical patients: the Prospective Evaluation of Dalteparin efficacy for Prevention of Venous Thromboembolism in Immobilized Patients Trial (the PREVENT study)
The PREVENT Investigator Group
Vasc Med 2002;7:269-273.
ABSTRACT  

Extended Venous Thromboembolism Prophylaxis After Total Hip Replacement: A Comparison of Low-Molecular-Weight Heparin With Oral Anticoagulant
Samama et al.
Arch Intern Med 2002;162:2191-2196.
ABSTRACT | FULL TEXT  

Extended Out-of-Hospital Low-Molecular-Weight Heparin for Prophylaxis against Deep Venous Thrombosis
Hull et al.
ANN INTERN MED 2002;137:621-621.
FULL TEXT  

Prolonged Thromboprophylaxis With Oral Anticoagulants After Total Hip Arthroplasty: A Prospective Controlled Randomized Study
Prandoni et al.
Arch Intern Med 2002;162:1966-1971.
ABSTRACT | FULL TEXT  

Preoperative or Postoperative Start of Prophylaxis for Venous Thromboembolism With Low-Molecular-Weight Heparin in Elective Hip Surgery?
Strebel et al.
Arch Intern Med 2002;162:1451-1456.
ABSTRACT | FULL TEXT  

Short-Duration Prophylaxis Against Venous Thromboembolism After Total Hip or Knee Replacement: A Meta-analysis of Prospective Studies Investigating Symptomatic Outcomes
Douketis et al.
Arch Intern Med 2002;162:1465-1471.
ABSTRACT | FULL TEXT  

Plasma D-Dimers in the Diagnosis of Venous Thromboembolism
Kelly et al.
Arch Intern Med 2002;162:747-756.
ABSTRACT | FULL TEXT  

Difference in Mortality After Hip Fracture is Associated with Postdischarge Prescription of Antithrombotic Prophylaxis: A Case-Control Study
Grion et al.
CLIN APPL THROMB HEMOST 2002;8:143-146.
ABSTRACT  

Duration of Prophylaxis against Venous Thromboembolism with Enoxaparin after Surgery for Cancer
Bergqvist et al.
NEJM 2002;346:975-980.
ABSTRACT | FULL TEXT  

Prevention of Venous Thromboembolism with Fondaparinux
Murashige et al.
NEJM 2002;346:940-942.
FULL TEXT  

Prophylaxis Against Venous Thromboembolic Disease in Patients Having a Total Hip or Knee Arthroplasty
Sculco et al.
JBJS 2002;84:466-477.
FULL TEXT  

Extended Out-of-Hospital Low-Molecular-Weight Heparin Prophylaxis against Deep Venous Thrombosis in Patients after Elective Hip Arthroplasty: A Systematic Review
Hull et al.
ANN INTERN MED 2001;135:858-869.
ABSTRACT | FULL TEXT  

Low-Molecular-Weight Heparins: Weeks or Months Instead of Days of Treatment
Kher and Samama
CLIN APPL THROMB HEMOST 2001;7:314-320.
ABSTRACT  

Prevention of post-discharge venous thromboembolism in patients with rheumatoid arthritis undergoing knee or hip arthroplasty: a continuing matter of debate
NURMOHAMED and DIJKMANS
Ann Rheum Dis 2001;60:905-907.
FULL TEXT  

Timing of Initial Administration of Low-Molecular-Weight Heparin Prophylaxis Against Deep Vein Thrombosis in Patients Following Elective Hip Arthroplasty: A Systematic Review
Hull et al.
Arch Intern Med 2001;161:1952-1960.
ABSTRACT | FULL TEXT  

Dalteparin vs Warfarin in Hip Arthroplasty Patients
Bajjoka et al.
Arch Intern Med 2001;161:776-777.
FULL TEXT  

Prevention of Venous Thromboembolism
Geerts et al.
Chest 2001;119 :132S-175S.
FULL TEXT