Geno Merli, MD; Theodore E. Spiro, MD; Carl-Gustav Olsson, MD, PhD; Ulrich Abildgaard, MD, PhD; Bruce L. Davidson, MD, MPH; Amiram Eldor, MD; Darlene Elias, MD; Andrew Grigg, MBBS; Dominique Musset, MD; George M. Rodgers, MD, PhD; Arthur A. Trowbridge, MD; Roger D. Yusen, MD; Krystyna Zawilska, MD; Enoxaparin Clinical Trial Group*
Grant Support: By Aventis Pharmaceuticals, Inc., Bridgewater, New Jersey, and Aventis Pharma SA, Antony, France (formerly known as Rhône-Poulenc Rorer Pharmaceuticals, Inc., Collegeville, Pennsylvania, and Rhône-Poulenc Rorer SA, Antony, France).
Requests for Single Reprints: Theodore E. Spiro, MD, Aventis Pharma SA, Cardiovascular Therapeutic Area, 20 Avenue Raymond Aron, 92165 Antony Cedex, France; e-mail, email@example.com.
Current Author Addresses: Dr. Merli: Division of Internal Medicine, Thomas Jefferson University, 3rd Floor, 211 South Ninth Street, Philadelphia, PA 19107.
Dr. Spiro: Cardiovascular Therapeutic Area, Aventis Pharma SA, 20 Avenue Raymond Aron, 92165 Antony Cedex, France.
Dr. Olsson: Medical Department, University Hospital of Lund, S 22185 Lund, Sweden.
Dr. Abildgaard: Medical Department, Aker Hospital, 0514 Oslo, Norway.
Dr. Davidson: Pulmonary and Critical Care, Virginia Mason Medical Center, C7-PUL, 1100 Ninth Avenue, Seattle, WA 98101.
Dr. Eldor: Institute of Hematology, Tel-Aviv Souraski Medical Center, Tel Aviv 63409, Israel.
Dr. Elias: Chest and Critical Care Medicine, Scripps Clinic and Research Foundation, 10666 North Torrey Pines Road, Mailstop 207 W, La Jolla, CA 92037.
Dr. Grigg: Department of Haematology, Royal Melbourne Hospital, Grattan Street, Victoria 3052, Australia.
Dr. Musset: Hôpital Antoine Béclère. 157 rue de la Porte de Trivaux, 92140 Clamart, France.
Dr. Rodgers: Hematology-Oncology Division, University of Utah Medical Center, 50 North Medical Drive, Salt Lake City, UT 84132.
Dr. Trowbridge: Division of Hematology/Oncology, Scott and White Clinic, Texas A&M University, College of Medicine, 2401 South 31st Street, Temple, TX 76508.
Dr. Yusen: Divisions of Pulmonary and Critical Care Medicine and General Medical Sciences, Washington University School of Medicine, Campus Box 8052, Barnes-Jewish Hospital, 660 South Euclid Avenue, Saint Louis, MO 63110-1093.
Dr. Zawilska: Department of Haematology, Academy of Medicine, Ul. Szkolna 8/12, 61-833 Poznan, Poland.
Author Contributions: Conception and design: G. Merli, T.E. Spiro, C.-G. Olsson, U. Abildgaard, B.L. Davidson, A.A. Trowbridge.
Analysis and interpretation of the data: G. Merli, T.E. Spiro, C.-G. Olsson, U. Abildgaard, B.L. Davidson, A. Eldor, D. Elias, A. Grigg, D. Musset, G.M. Rodgers, R.D. Yusen.
Drafting of the article: G. Merli, T.E. Spiro, C.-G. Olsson, U. Abildgaard, B.L. Davidson, A. Eldor, D. Elias, G.M. Rodgers, A.A. Trowbridge, R.D. Yusen.
Critical revision of the article for important intellectual content: G. Merli, T.E. Spiro, C.-G. Olsson, U. Abildgaard, B.L. Davidson, A. Eldor, D. Elias, A. Grigg, D. Musset, G.M. Rodgers, A.A. Trowbridge, R.D. Yusen, K. Zawilska.
Final approval of the article: G. Merli, T.E. Spiro, C.-G. Olsson, B.L. Davidson, A. Eldor, A. Grigg, A.A. Trowbridge, R.D. Yusen, K. Zawilska.
Provision of study materials or patients: T.E. Spiro, C.-G. Olsson, U. Abildgaard, B.L. Davidson, A. Eldor, D. Elias, A. Grigg, D. Musset, G.M. Rodgers, A.A. Trowbridge, R.D. Yusen, K. Zawilska.
Statistical expertise: T.E. Spiro, B.L. Davidson, R.D. Yusen.
Obtaining of funding: T.E. Spiro.
Administrative, technical, or logistic support: T.E. Spiro.
Collection and assembly of data: T.E. Spiro, B.L. Davidson, A.A. Trowbridge, R.D. Yusen.
Merli G, Spiro TE, Olsson C, Abildgaard U, Davidson BL, Eldor A, et al. Subcutaneous Enoxaparin Once or Twice Daily Compared with Intravenous Unfractionated Heparin for Treatment of Venous Thromboembolic Disease. Ann Intern Med. 2001;134:191-202. doi: 10.7326/0003-4819-134-3-200102060-00009
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Published: Ann Intern Med. 2001;134(3):191-202.
Venous thromboembolic disease causes significant morbidity and mortality in both hospitalized and nonhospitalized patients. The mean annual incidence in the United States is 48 per 100 000 for deep venous thrombosis and 23 per 100 000 for pulmonary embolism, according to an epidemiologic study conducted in Massachusetts (1). A similar study in Sweden showed an annual incidence of 160 new cases of deep venous thrombosis per 100 000 inhabitants (2).
Five to 10 days of unfractionated heparin is a common recommended initial treatment for deep venous thrombosis. This treatment maintains the activated partial thromboplastin time above 1.5 times its control value (3, 4), as calibrated by protamine titration or an anti–factor Xa assay. Another recommended initial treatment is 5 to 10 days of weight-adjusted low-molecular-weight heparin followed by at least 3 months of oral anticoagulant therapy (3-7). Low-molecular-weight heparins are now frequently being used in place of unfractionated heparin for both prevention and treatment of venous thromboembolism (3, 8). Randomized trials and meta-analyses have shown subcutaneously administered low-molecular-weight heparins to have antithrombotic efficacy equal to (9-12) or greater than (13-16) that of continuously infused unfractionated heparin in the initial treatment of deep venous thrombosis and equal to that of unfractionated heparin in the treatment of pulmonary embolism (17, 18). However, many of these studies enrolled small numbers of patients (9-13, 15, 16), used primarily venographic plethysmographic or scintigraphic end points (9-11, 13, 16), and sometimes excluded patients with pulmonary embolism (11, 15). Most trials of twice-daily low-molecular-weight heparin adjusted treatment regimens according to patient weight without laboratory monitoring. However, several studies suggest that once-daily weight-adjusted dosage of a low-molecular-weight heparin is as effective in the treatment of proximal deep venous thrombosis as adjusted dosages of intravenous unfractionated heparin (14, 19) or twice-daily low-molecular-weight heparin (20).
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Venous Thromboembolism, Prevention/Screening.
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