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 ISI (213)  • Contact me when this article is cited  Related Content  • Related letters  • Similar articles in this journal  Topic Collections  • Thrombolysis  • Venous Thromboembolism  • Cardiovascular System  • Randomized Controlled Trial  • Adverse Effects  • Alert me on articles by topic  Social Bookmarking   What's this?

A Randomized Controlled Study

Guy Meyer, MD; Zora Marjanovic, MD; Judith Valcke, MD; Bernard Lorcerie, MD; Yves Gruel, MD; Philippe Solal-Celigny, MD; Christine Le Maignan, MD; Jean Marc Extra, MD; Paul Cottu, MD; Dominique Farge, MD

Arch Intern Med. 2002;162:1729-1735.

Background  The use of warfarin sodium for treating venous thromboembolism in patients with cancer is associated with a significant risk of recurrence and bleeding. The use of low-molecular-weight heparin sodium for secondary prevention of venous thromboembolism in cancer patients may reduce the complication rate.

Objective  To determine whether a fixed dose of subcutaneous low-molecular-weight heparin is superior to oral warfarin for the secondary prophylaxis of venous thromboembolism in patients with cancer and venous thromboembolism.

Methods  In a randomized, open-label multicenter trial performed between April 1995 and March 1999, we compared subcutaneous enoxaparin sodium (1.5 mg/kg once a day) with warfarin given for 3 months in 146 patients with venous thromboembolism and cancer.

Main Outcome Measure  A combined outcome event defined as major bleeding or recurrent venous thromboembolism within 3 months.

Results  Of the 71 evaluable patients assigned to receive warfarin, 15 (21.1%; 95% confidence interval [CI], 12.3%-32.4%) experienced one major outcome event compared with 7 (10.5%) of the 67 evaluable patients assigned to receive enoxaparin (95% CI, 4.3%-20.3%; P = .09). There were 6 deaths owing to hemorrhage in the warfarin group compared with none in the enoxaparin group. In the warfarin group, 17 patients (22.7%) died (95% CI, 13.8%-33.8%) compared with 8 (11.3%) in the enoxaparin group (95% CI, 5.0%-21.0%; P = .07). No difference was observed regarding the progression of the underlying cancer or cancer-related death.

Conclusions  These results confirm that warfarin is associated with a high bleeding rate in patients with venous thromboembolism and cancer. Prolonged treatment with low-molecular-weight heparin may be as effective as oral anticoagulants and may be safer in these cancer patients.

From the Department of Respiratory and Critical Care Medicine, Hôpital Européen Georges Pompidou, Paris V University, Paris, France (Drs Meyer and Valcke); Department of Internal Medicine, Hôpital Saint Louis, Paris VII University, Paris (Drs Marjanovic and Farge); Department of Internal Medicine, Hôpital du Bocage, and Dijon University, Dijon, France (Dr Lorcerie); Department of Haematology, Hôpital Trousseau, and Tours University, Tours, France (Dr Gruel); Department of Medical Oncology, Clinique Victor Hugo, Le Mans, France (Dr Solal-Celigny); Department of Medical Oncology, Hôpital Européen Georges Pompidou, Paris (Dr Le Maignan); and Department of Medical Oncology, Hôpital Saint-Louis, Paris (Drs Extra and Cottu).

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

RELATED LETTERS

International Normalized Ratio and Anticoagulation
Michael R. Theerman
Arch Intern Med. 2003;163(10):1242-1243.
EXTRACT | FULL TEXT  

Apparent Warfarin Potency Inconsistencies Compromise Effectiveness
Bruce M. Rothschild
Arch Intern Med. 2003;163(10):1243.
EXTRACT | FULL TEXT  

Is Low-Molecular-Weight Heparin Safer Than Warfarin for Secondary Prevention of Venous Thromboembolism in Cancer Patients?
Graham J. Caine and Gregory Y. H. Lip
Arch Intern Med. 2003;163(10):1243-1244.
EXTRACT | FULL TEXT  

Is Low-Molecular-Weight Heparin Safer Than Warfarin for Secondary Prevention of Venous Thromboembolism in Cancer Patients?—Reply
Guy Meyer and Dominique Farge
Arch Intern Med. 2003;163(10):1244.
EXTRACT | FULL TEXT  

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES

Cancer and thrombosis: implications of published guidelines for clinical practice
Khorana
Ann Oncol 2009;0:mdp068v1-mdp068.
ABSTRACT | FULL TEXT  

Management of venous thromboembolism in cancer patients: ESMO Clinical Recommendations
Mandala et al.
Ann Oncol 2009;20:iv182-iv184.
FULL TEXT  

Venous Thromboembolism: Risk Factors for Recurrence
Zhu et al.
Arterioscler. Thromb. Vasc. Bio. 2009;29:298-310.
ABSTRACT | FULL TEXT  

Cancer and clots: All cases of venous thromboembolism are not treated the same
BABU and CARMAN
Cleveland Clinic Journal of Medicine 2009;76:129-135.
ABSTRACT | FULL TEXT  

Treatment of Venous Thromboembolism in Patients with Cancer
Lee
Am Soc Clin Oncol Ed Book 2009;2009:331-336.
ABSTRACT | FULL TEXT  

Recurrent thromboembolism and major bleeding during oral anticoagulant therapy in patients with solid cancer: findings from the RIETE registry
Prandoni et al.
haematol 2008;93:1432-1434.
FULL TEXT  

Hemorrhagic Complications of Anticoagulant and Thrombolytic Treatment: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition)
Schulman et al.
Chest 2008;133:257S-298S.
ABSTRACT | FULL TEXT  

Antithrombotic Therapy for Venous Thromboembolic Disease: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition)
Kearon et al.
Chest 2008;133:454S-545S.
ABSTRACT | FULL TEXT  

Improving the effectiveness of interventions in palliative care: the potential role of qualitative research in enhancing evidence from randomized controlled trials
Flemming et al.
Palliat Med 2008;22:123-131.
ABSTRACT  

New Anticoagulants for Treatment of Venous Thromboembolism
Gross and Weitz
Arterioscler. Thromb. Vasc. Bio. 2008;28:380-386.
ABSTRACT | FULL TEXT  

Clinical characteristics and management of cancer-associated acute venous thromboembolism: findings from the MASTER Registry
Imberti et al.
haematol 2008;93:273-278.
ABSTRACT | FULL TEXT  

Anticoagulation in the Treatment of Venous Thromboembolism in Patients with Cancer
Falanga et al.
Am Soc Clin Oncol Ed Book 2008;2008:258-268.
ABSTRACT | FULL TEXT  

American Society of Clinical Oncology Guideline: Recommendations for Venous Thromboembolism Prophylaxis and Treatment in Patients With Cancer
Lyman et al.
JCO 2007;25:5490-5505.
ABSTRACT | FULL TEXT  

The challenges of managing cancer related venous thromboembolism in the palliative care setting
Noble
Postgrad. Med. J. 2007;83:671-674.
ABSTRACT | FULL TEXT  

Trousseau's syndrome: multiple definitions and multiple mechanisms
Varki
Blood 2007;110:1723-1729.
ABSTRACT | FULL TEXT  

The use of long-term low-molecular weight heparin for the treatment of venous thromboembolism in palliative care patients with advanced cancer: a case series of sixty two patients
Noble et al.
Palliat Med 2007;21:473-476.
ABSTRACT  

Low-molecular-weight heparin in cancer-associated thrombosis: treatment, secondary prevention, and survival
Nishioka and Goodin
J Oncol Pharm Pract 2007;13:85-97.
ABSTRACT  

Assessing, preventing, and treating venous thromboembolism: Evidence-based approaches
Nutescu
Am J Health Syst Pharm 2007;64:S5-S13.
ABSTRACT | FULL TEXT  

Anticoagulants in heart disease: current status and perspectives
De Caterina et al.
Eur Heart J 2007;0:ehl492v1-34.
FULL TEXT  

Treatment of Deep Vein Thrombosis With Enoxaparin in Pediatric Cancer Patients Receiving Chemotherapy
Stine et al.
CLIN APPL THROMB HEMOST 2007;13:161-165.
ABSTRACT  

Does low-molecular-weight heparin influence cancer-related mortality?
Meyer
Ann Oncol 2007;18:609-610.
FULL TEXT  

Management of Venous Thromboembolism: A Clinical Practice Guideline from the American College of Physicians and the American Academy of Family Physicians
Snow et al.
ANN INTERN MED 2007;146:204-210.
ABSTRACT | FULL TEXT  

Management of Venous Thromboembolism: A Systematic Review for a Practice Guideline
Segal et al.
ANN INTERN MED 2007;146:211-222.
ABSTRACT | FULL TEXT  

Management of Venous Thromboembolism: A Clinical Practice Guideline from the American College of Physicians and the American Academy of Family Physicians
Snow et al.
Ann Fam Med 2007;5:74-80.
ABSTRACT | FULL TEXT  

Is Recurrent Venous Thromboembolism After Therapy Reduced by Low-Molecular-Weight Heparin Compared With Oral Anticoagulants?
Ferretti et al.
Chest 2006;130:1808-1816.
ABSTRACT | FULL TEXT  

Secondary Prevention of Venous Thromboembolic Events in Patients With Active Cancer: Enoxaparin Alone Versus Initial Enoxaparin Followed by Warfarin for a 180-Day Period
Deitcher et al.
CLIN APPL THROMB HEMOST 2006;12:389-396.
ABSTRACT  

Does low-molecular-weight heparin influence cancer-related mortality?
Ferretti et al.
Ann Oncol 2006;17:1604-1606.
FULL TEXT  

Risk factors for venous thromboembolic events in cancer patients
Kroger et al.
Ann Oncol 2006;17:297-303.
ABSTRACT | FULL TEXT  

Dalteparin for prevention of catheter-related complications in cancer patients with central venous catheters: final results of a double-blind, placebo-controlled phase III trial
Karthaus et al.
Ann Oncol 2006;17:289-296.
ABSTRACT | FULL TEXT  

How I treat venous thromboembolism in patients with cancer
Prandoni
Blood 2005;106:4027-4033.
ABSTRACT | FULL TEXT  

Selecting an anticoagulant for recurrent venous thromboembolism in cancer
Goodin
Am J Health Syst Pharm 2005;62:S10-S13.
ABSTRACT | FULL TEXT  

Extended enoxaparin monotherapy for acute symptomatic pulmonary embolism
Kucher et al.
Vasc Med 2005;10:251-256.
ABSTRACT  

Low-Molecular-Weight Heparin Versus Oral Anticoagulant Therapy for the Long-Term Treatment of Symptomatic Venous Thromboembolism: Is There Any Difference in Cancer-Related Mortality?
Ferretti et al.
JCO 2005;23:7248-7250.
FULL TEXT  

Deep vein thrombosis in cancer: the scale of the problem and approaches to management
Falanga and Zacharski
Ann Oncol 2005;16:696-701.
ABSTRACT | FULL TEXT  

Is long-term low-molecular-weight heparin acceptable to palliative care patients in the treatment of cancer related venous thromboembolism? A qualitative study
Noble and Finlay
Palliat Med 2005;19:197-201.
ABSTRACT  

Ximelagatran vs Low-Molecular-Weight Heparin and Warfarin for the Treatment of Deep Vein Thrombosis: A Randomized Trial
Fiessinger et al.
JAMA 2005;293:681-689.
ABSTRACT | FULL TEXT  

Low-Molecular-Weight Heparin for the Treatment of Venous Thromboembolism in the Elderly
Pineo and Hull
CLIN APPL THROMB HEMOST 2005;11:15-23.
ABSTRACT  

Warfarin Versus Low-Molecular-Weight Heparin Therapy in Cancer Patients
Zacharski et al.
The Oncologist 2005;10:72-79.
ABSTRACT | FULL TEXT  

Anticoagulation in Hypercoagulable Conditions: Special Considerations in the Treatment and Prevention of Venous Thromboembolism
Wittkowsky
Journal of Pharmacy Practice 2004;17:308-316.
ABSTRACT  

Hemorrhagic Complications of Anticoagulant Treatment: The Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy
Levine et al.
Chest 2004;126:287S-310S.
ABSTRACT | FULL TEXT  

Long-Term Management of Patients After Venous Thromboembolism
Kearon
Circulation 2004;110:I-10-I-18.
ABSTRACT | FULL TEXT  

Prevention of Recurrent Deep Venous Thrombosis with Sulodexide: The SanVal Registry
Errichi et al.
ANGIOLOGY 2004;55:243-249.
ABSTRACT  

Deep Venous Thrombosis
Lopez et al.
ASH Education Book 2004;2004:439-456.
ABSTRACT | FULL TEXT  

Anticoagulation or Inferior Vena Cava Filter Placement for Patients With Primary Intracerebral Hemorrhage Developing Venous Thromboembolism?
Kelly et al.
Stroke 2003;34:2999-3005.
ABSTRACT | FULL TEXT  

Venous Thromboembolism Associated With Long-Term Use of Central Venous Catheters in Cancer Patients
Verso and Agnelli
JCO 2003;21:3665-3675.
ABSTRACT | FULL TEXT  

Care of Patients Receiving Long-Term Anticoagulant Therapy
Schulman
NEJM 2003;349:675-683.
FULL TEXT  

Low-Molecular-Weight Heparin versus a Coumarin for the Prevention of Recurrent Venous Thromboembolism in Patients with Cancer
Lee et al.
NEJM 2003;349:146-153.
ABSTRACT | FULL TEXT  

Apparent Warfarin Potency Inconsistencies Compromise Effectiveness
Rothschild
Arch Intern Med 2003;163:1243-1243.
FULL TEXT  

Is Low-Molecular-Weight Heparin Safer Than Warfarin for Secondary Prevention of Venous Thromboembolism in Cancer Patients?--Reply
Meyer and Farge
Arch Intern Med 2003;163:1244-1244.
FULL TEXT  

International Normalized Ratio and Anticoagulation
Theerman
Arch Intern Med 2003;163:1242-1243.
FULL TEXT  

Is Low-Molecular-Weight Heparin Safer Than Warfarin for Secondary Prevention of Venous Thromboembolism in Cancer Patients?
Caine and Lip
Arch Intern Med 2003;163:1243-1244.
FULL TEXT  

In patients with cancer and venous thromboembolism (VTE), enoxaparin was as effective as warfarin for VTE prophylaxis and reduced fatal haemorrhage
Scott
Evid. Based Med. 2003;8:85-85.
FULL TEXT  

Thrombotic Disorders: Diagnosis and Treatment
Schafer et al.
ASH Education Book 2003;2003:520-539.
ABSTRACT | FULL TEXT