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; for the 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, firstname.lastname@example.org.
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.
Low-molecular-weight heparins administered subcutaneously once or twice daily have been reported to be as safe and efficacious as intravenous unfractionated heparin in the treatment of acute venous thromboembolic disease.
To determine whether subcutaneous enoxaparin administered once or twice daily is as effective as continuously infused unfractionated heparin in acute symptomatic venous thromboembolic disease.
Randomized, controlled, partially blinded equivalence trial.
74 hospitals in 16 countries.
900 patients with symptomatic lower-extremity deep venous thrombosis, including 287 (32%) with confirmed pulmonary embolism.
Initial therapy with dose-adjusted intravenous unfractionated heparin compared with subcutaneous enoxaparin at fixed dosages of 1.0 mg/kg of body weight twice daily or 1.5 mg/kg once daily. Long-term oral anticoagulation was started in all patients within 72 hours of randomization.
Clinical end points assessed during a 3-month follow-up period.
Equivalent efficacy was seen in the heparin group and both enoxaparin groups. Symptomatic venous thromboembolism recurred in 12 of 290 patients receiving unfractionated heparin (4.1%), 13 of 298 patients receiving once-daily enoxaparin (4.4%), and 9 of 312 patients receiving twice-daily enoxaparin (2.9%). Compared with unfractionated heparin, the treatment difference was 0.2% (95% CI, −3.04% to 3.49%) for once-daily enoxaparin and −1.2% (CI, −4.2% to 1.7%) for twice-daily enoxaparin. Incidence of major hemorrhage did not differ among the three treatment groups. Major hemorrhage occurred in 6 of 290 patients (2.1%) in the unfractionated heparin group, 5 of 298 patients (1.7%) in the once-daily enoxaparin group, and 4 of 312 patients (1.3%) in the twice-daily enoxaparin group.
Subcutaneous enoxaparin once or twice daily is as effective and safe as dose-adjusted, continuously infused unfractionated heparin in the prevention of recurrent symptomatic venous thromboembolic disease.
*For members of the Enoxaparin Clinical Trial Group and other study participants, see Appendix.
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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.
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