BACKGROUND. In most countries, heparin is used in the initial treatment of patients with deep-vein thrombosis. Well-designed studies establishing the efficacy of heparin therapy are lacking, however. Treatment with acenocoumarol alone, according to the hypothesis that high dosages of oral anticoagulants obviate the need for heparin, is considered an effective alternative in some countries. METHODS. In a randomized, double-blind study we compared the efficacy and safety of continuous intravenous heparin plus acenocoumarol with the efficacy and safety of acenocoumarol alone in the initial treatment of outpatients with proximal-vein thrombosis. The principal study end point was a confirmed symptomatic extension or recurrence of venous thromboembolism during six months of follow-up. In addition, we assessed asymptomatic extension or pulmonary embolism by repeating venography and lung scanning after the first week of treatment. The incidence of major bleeding was determined during three months of follow-up. RESULTS. The study was terminated early by the Data Safety and Monitoring Committee because of an excess of symptomatic events in the group that received acenocoumarol alone (in 12 of 60 patients [20 percent], as compared with 4 of 60 patients [6.7 percent] in the combined-therapy group by intention-to-treat analysis; P = 0.058). Asymptomatic extension of venous thrombosis was observed in 39.6 percent of the patients in the acenocoumarol group and in 8.2 percent of patients treated with heparin plus acenocoumarol (P < 0.001). Major bleeding complications were infrequent and comparable in the two groups. CONCLUSIONS. Patients with proximal-vein thrombosis require initial treatment with full-dose heparin, which can safely be combined with acenocoumarol therapy.
Source Information
Center for Haemostasis, Thrombosis, Atherosclerosis and Inflammation Research, Academic Medical Center, Amsterdam, The Netherlands.
This article has been cited by other articles:
Stein, P. D., Hull, R. D., Matta, F., Yaekoub, A. Y.
(2009). Anticoagulant Therapy for Acute Venous Thromboembolism: What We Think We Know and What the Data Show for the Timing of Recurrent Events. CLIN APPL THROMB HEMOST
15: 609-612
[Abstract]
Authors/Task Force Members, , Torbicki, A., Perrier, A., Konstantinides, S., Agnelli, G., Galie, N., Pruszczyk, P., Bengel, F., Brady, A. J.B., Ferreira, D., Janssens, U., Klepetko, W., Mayer, E., Remy-Jardin, M., Bassand, J.-P., ESC Committee for Practice Guidelines (CPG), , Vahanian, A., Camm, J., De Caterina, R., Dean, V., Dickstein, K., Filippatos, G., Funck-Brentano, C., Hellemans, I., Kristensen, S. D., McGregor, K., Sechtem, U., Silber, S., Tendera, M., Widimsky, P., Zamorano, J. L., Document Reviewers, , Zamorano, J.-L., Andreotti, F., Ascherman, M., Athanassopoulos, G., De Sutter, J., Fitzmaurice, D., Forster, T., Heras, M., Jondeau, G., Kjeldsen, K., Knuuti, J., Lang, I., Lenzen, M., Lopez-Sendon, J., Nihoyannopoulos, P., Perez Isla, L., Schwehr, U., Torraca, L., Vachiery, J.-L.
(2008). Guidelines on the diagnosis and management of acute pulmonary embolism: The Task Force for the Diagnosis and Management of Acute Pulmonary Embolism of the European Society of Cardiology (ESC). Eur Heart J
29: 2276-2315
[Full Text]
Schulman, S., Beyth, R. J., Kearon, C., Levine, M. N.
(2008). Hemorrhagic Complications of Anticoagulant and Thrombolytic Treatment: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest
133: 257S-298S
[Abstract][Full Text]
Kearon, C., Kahn, S. R., Agnelli, G., Goldhaber, S., Raskob, G. E., Comerota, A. J.
(2008). Antithrombotic Therapy for Venous Thromboembolic Disease: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest
133: 454S-545S
[Abstract][Full Text]
The van Gogh Investigators,
(2007). Idraparinux versus Standard Therapy for Venous Thromboembolic Disease. NEJM
357: 1094-1104
[Abstract][Full Text]
Scarvelis, D., Wells, P. S.
(2006). Diagnosis and treatment of deep-vein thrombosis.. CMAJ
175: 1087-1092
[Abstract][Full Text]
Cirujeda, J. L., Granado, P. C.
(2006). A Study on the Safety, Efficacy, and Efficiency of Sulodexide Compared with Acenocoumarol in Secondary Prophylaxis in Patients with Deep Venous Thrombosis. ANGIOLOGY
57: 53-64
[Abstract]
Prandoni, P.
(2005). How I treat venous thromboembolism in patients with cancer. Blood
106: 4027-4033
[Abstract][Full Text]
Elliott, C. G., Goldhaber, S. Z., Jensen, R. L.
(2005). Delays in Diagnosis of Deep Vein Thrombosis and Pulmonary Embolism. Chest
128: 3372-3376
[Abstract][Full Text]
Mismetti, P., Quenet, S., Levine, M., Merli, G., Decousus, H., Derobert, E., Laporte, S.
(2005). Enoxaparin in the Treatment of Deep Vein Thrombosis With or Without Pulmonary Embolism: An Individual Patient Data Meta-analysis. Chest
128: 2203-2210
[Abstract][Full Text]
McBride, B. F.
(2005). A Preliminary Assessment of the Critical Differences Between Novel Oral Anticoagulants Currently in Development. J Clin Pharmacol
45: 1004-1017
[Abstract][Full Text]
The PREPIC Study Group,
(2005). Eight-Year Follow-Up of Patients With Permanent Vena Cava Filters in the Prevention of Pulmonary Embolism: The PREPIC (Prevention du Risque d'Embolie Pulmonaire par Interruption Cave) Randomized Study. Circulation
112: 416-422
[Abstract][Full Text]
Rathbun, S. W., Whitsett, T. L., Raskob, G. E.
(2004). Negative D-dimer Result To Exclude Recurrent Deep Venous Thrombosis: A Management Trial. ANN INTERN MED
141: 839-845
[Abstract][Full Text]
McGuire, M., Dobesh, P. P.
(2004). Therapeutic Update on the Prevention and Treatment of Venous Thromboembolism. Journal of Pharmacy Practice
17: 289-307
[Abstract]
Levine, M. N., Raskob, G., Beyth, R. J., Kearon, C., Schulman, S.
(2004). Hemorrhagic Complications of Anticoagulant Treatment: The Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest
126: 287S-310S
[Abstract][Full Text]
Buller, H. R., Agnelli, G., Hull, R. D., Hyers, T. M., Prins, M. H., Raskob, G. E.
(2004). Antithrombotic Therapy for Venous Thromboembolic Disease: The Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest
126: 401S-428S
[Abstract][Full Text]
Weitz, J. I.
(2004). New Anticoagulants for Treatment of Venous Thromboembolism. Circulation
110: I-19-I-26
[Abstract][Full Text]
Bates, S. M., Ginsberg, J. S.
(2004). Treatment of Deep-Vein Thrombosis. NEJM
351: 268-277
[Full Text]
Stevens, S. M., Elliott, C. G., Chan, K. J., Egger, M. J., Ahmed, K. M.
(2004). Withholding Anticoagulation after a Negative Result on Duplex Ultrasonography for Suspected Symptomatic Deep Venous Thrombosis. ANN INTERN MED
140: 985-991
[Abstract][Full Text]
Buller, H. R., Davidson, B. L., Decousus, H., Gallus, A., Gent, M., Piovella, F., Prins, M. H., Raskob, G., Segers, A. E.M., Cariou, R., Leeuwenkamp, O., Lensing, A. W.A., The Matisse Investigators*,
(2004). Fondaparinux or Enoxaparin for the Initial Treatment of Symptomatic Deep Venous Thrombosis: A Randomized Trial. ANN INTERN MED
140: 867-873
[Abstract][Full Text]
Prandoni, P.
(2004). Toward the Simplification of Antithrombotic Treatment of Venous Thromboembolism. ANN INTERN MED
140: 925-926
[Full Text]
Writing Committee for the Galilei Investigators,
(2004). Subcutaneous Adjusted-Dose Unfractionated Heparin vs Fixed-Dose Low-Molecular-Weight Heparin in the Initial Treatment of Venous Thromboembolism. Arch Intern Med
164: 1077-1083
[Abstract][Full Text]
Linkins, L.-A., Choi, P. T., Douketis, J. D.
(2003). Clinical Impact of Bleeding in Patients Taking Oral Anticoagulant Therapy for Venous Thromboembolism: A Meta-Analysis. ANN INTERN MED
139: 893-900
[Abstract][Full Text]
The Matisse Investigators,
(2003). Subcutaneous Fondaparinux versus Intravenous Unfractionated Heparin in the Initial Treatment of Pulmonary Embolism. NEJM
349: 1695-1702
[Abstract][Full Text]
Buller, H. R., Prins, M. H.
(2003). Secondary Prophylaxis with Warfarin for Venous Thromboembolism. NEJM
349: 702-704
[Full Text]
van Dongen, C. J. J., Vink, R., Hutten, B. A., Buller, H. R., Prins, M. H.
(2003). The Incidence of Recurrent Venous Thromboembolism After Treatment With Vitamin K Antagonists in Relation to Time Since First Event: A Meta-analysis. Arch Intern Med
163: 1285-1293
[Abstract][Full Text]
Dalen, J. E.
(2002). Pulmonary Embolism: What Have We Learned Since Virchow?: Treatment and Prevention. Chest
122: 1801-1817
[Full Text]
Hirsh, J., Bates, S.
(2002). Questioning the Treatment of Venous Thromboembolism. ANN INTERN MED
137: 145-145
[Full Text]
Cundiff, D. K.
(2002). Significant Omission in Antithrombotic Supplement. Chest
121: 1378-1379
[Full Text]
Tait, R C
(2001). Anticoagulation in patients with thromboembolic disease. Thorax
56: ii30-37
[Full Text]
Hirsh, J., Anand, S. S., Halperin, J. L., Fuster, V.
(2001). Guide to Anticoagulant Therapy: Heparin : A Statement for Healthcare Professionals From the American Heart Association. Arterioscler. Thromb. Vasc. Bio.
21
: e9-e9
[Full Text]
Hirsh, J., Anand, S. S., Halperin, J. L., Fuster, V.
(2001). Guide to Anticoagulant Therapy: Heparin : A Statement for Healthcare Professionals From the American Heart Association. Circulation
103: 2994-3018
[Full Text]
Hirsh, J., Bates, S. M.
(2001). Clinical Trials That Have Influenced the Treatment of Venous Thromboembolism: A Historical Perspective. ANN INTERN MED
134: 409-417
[Abstract][Full Text]
Bates, S. M., Weitz, J. I., Johnston, M., Hirsh, J., Ginsberg, J. S.
(2001). Use of a Fixed Activated Partial Thromboplastin Time Ratio to Establish a Therapeutic Range for Unfractionated Heparin. Arch Intern Med
161: 385-391
[Abstract][Full Text]
Hirsh, J., Warkentin, T. E., Shaughnessy, S. G., Anand, S. S., Halperin, J. L., Raschke, R., Granger, C., Ohman, E. M., Dalen, J. E.
(2001). Heparin and Low-Molecular-Weight Heparin Mechanisms of Action, Pharmacokinetics, Dosing, Monitoring, Efficacy, and Safety. Chest
119
: 64S-94S
[Full Text]
Levine, M. N., Raskob, G., Landefeld, S., Kearon, C.
(2001). Hemorrhagic Complications of Anticoagulant Treatment. Chest
119
: 108S-121S
[Full Text]
Geerts, W. H., Heit, J. A., Clagett, G. P., Pineo, G. F., Colwell, C. W., Anderson, F. A. Jr., Wheeler, H. B.
(2001). Prevention of Venous Thromboembolism. Chest
119
: 132S-175S
[Full Text]
Hyers, T. M., Agnelli, G., Hull, R. D., Morris, T. A., Samama, M., Tapson, V., Weg, J. G.
(2001). Antithrombotic Therapy for Venous Thromboembolic Disease. Chest
119
: 176S-193S
[Full Text]
(2000). Treatment of Proximal Deep Vein Thrombosis With a Novel Synthetic Compound (SR90107A/ORG31540) With Pure Anti-Factor Xa Activity : A Phase II Evaluation. Circulation
102: 2726-2731
[Abstract][Full Text]
Zidane, M., Schram, M. T., Planken, E. W., Molendijk, W. H., Rosendaal, F. R., van der Meer, F. J. M., Huisman, M. V.
(2000). Frequency of Major Hemorrhage in Patients Treated With Unfractionated Intravenous Heparin for Deep Venous Thrombosis or Pulmonary Embolism: A Study in Routine Clinical Practice. Arch Intern Med
160: 2369-2373
[Abstract][Full Text]
(2000). Guidelines on diagnosis and management of acute pulmonary embolism. Eur Heart J
21: 1301-1336
White, R. H., Zhou, H., Kim, J., Romano, P. S.
(2000). A Population-Based Study of the Effectiveness of Inferior Vena Cava Filter Use Among Patients With Venous Thromboembolism. Arch Intern Med
160: 2033-2041
[Abstract][Full Text]
Heit, J. A., Mohr, D. N., Silverstein, M. D., Petterson, T. M., O'Fallon, W. M., Melton III, L. J.
(2000). Predictors of Recurrence After Deep Vein Thrombosis and Pulmonary Embolism: A Population-Based Cohort Study. Arch Intern Med
160: 761-768
[Abstract][Full Text]
DELLA VALLE, C. J., JAZRAWI, L. M., IDJADI, J., HIEBERT, R. N., STUCHIN, S. A., STEIGER, D. J., DI CESARE, P. E.
(2000). Anticoagulant Treatment of Thromboembolism with Intravenous Heparin Therapy in the Early Postoperative Period Following Total Joint Arthroplasty. JBJS
82: 207-12
[Abstract][Full Text]
Hull, R. D., Raskob, G. E., Brant, R. F., Pineo, G. F., Elliott, G., Stein, P. D., Gottschalk, A., Valentine, K. A., Mah, A. F., for the American-Canadian Thrombosis Study Group,
(2000). Low-Molecular-Weight Heparin vs Heparin in the Treatment of Patients With Pulmonary Embolism. Arch Intern Med
160: 229-236
[Abstract][Full Text]
Nicolaides, A.N., Cesarone, M.R., Laurora, G., De Sanctis, M.T., Incandela, L., Barsotti, A., Corsi, M., Vasdekis, S., Christopoulos, D., Lennox, A., Malouf, M., Belcaro, G.
(1999). Comparison of Low-Molecular-Weight Heparin, Administered Primarily at Home, with Unfractionated Heparin, Administered in Hospital, and Subcutaneous Heparin, Administered at Home for Deep-Vein Thrombosis. ANGIOLOGY
50: 781-787
[Abstract]
Verstraete, M.
(1999). Prevention and treatment of venous thromboembolism after major trauma. Trauma
1: 39-51
[Abstract]
Goldhaber, S. Z.
(1998). Pulmonary Embolism. NEJM
339: 93-104
[Full Text]
White, R. H., Zhou, H., Romano, P. S.
(1998). Length of Hospital Stay for Treatment of Deep Venous Thrombosis and the Incidence of Recurrent Thromboembolism. Arch Intern Med
158: 1005-1010
[Abstract][Full Text]
Decousus, H., Leizorovicz, A., Parent, F., Page, Y., Tardy, B., Girard, P., Laporte, S., Faivre, R., Charbonnier, B., Barral, F.-G., Huet, Y., Simonneau, G., The Prevention du Risque d'Embolie Pulmonaire par,
(1998). A Clinical Trial of Vena Caval Filters in the Prevention of Pulmonary Embolism in Patients with Proximal Deep-Vein Thrombosis. NEJM
338: 409-416
[Abstract][Full Text]
Douketis, J. D., Kearon, C., Bates, S., Duku, E. K., Ginsberg, J. S.
(1998). Risk of Fatal Pulmonary Embolism in Patients With Treated Venous Thromboembolism. JAMA
279: 458-462
[Abstract][Full Text]
Buller, H. R, Kraaijenhagen, R. A, Koopman, M. M.
(1998). Early discharge strategies following venous thrombosis. Vasc Med
3: 47-50
[Abstract]
Prandoni, P., Lensing, A. W., Prins, M. R
(1998). Long-term outcomes after deep venous thrombosis of the lower extremities. Vasc Med
3: 57-60
[Abstract]
Hull, R. D., Raskob, G. E., Brant, R. F., Pineo, G. F., Valentine, K. A.
(1997). Relation Between the Time to Achieve the Lower Limit of the APTT Therapeutic Range and Recurrent Venous Thromboembolism During Heparin Treatment for Deep Vein Thrombosis. Arch Intern Med
157: 2562-2568
[Abstract]
Hull, R. D., Raskob, G. E., Brant, R. F., Pineo, G. F., Valentine, K. A.
(1997). The Importance of Initial Heparin Treatment on Long-term Clinical Outcomes of Antithrombotic Therapy: The Emerging Theme of Delayed Recurrence. Arch Intern Med
157: 2317-2321
[Abstract]
Hirsh, J., Kearon, C., Ginsberg, J.
(1997). Duration of Anticoagulant Therapy After First Episode of Venous Thrombosis in Patients With Inherited Thrombophilia. Arch Intern Med
157: 2174-2177
[Abstract]
van den Belt, A. G. M., Sanson, B.-J., Simioni, P., Prandoni, P., Buller, H. R., Girolami, A., Prins, M. H.
(1997). Recurrence of Venous Thromboembolism in Patients With Familial Thrombophilia. Arch Intern Med
157: 2227-2232
[Abstract]
Becker, R. C., Ansell, J.
(1997). The Need for Long-Term Anticoagulants in Venous Thromboembolism: How Long?. CLIN APPL THROMB HEMOST
3: S8-S15
Anand, S., Ginsberg, J. S., Hirsh, J.
(1997). Is There a Relationship Between the Intensity of Heparin Treatment and Recurrent Thomboembolism?. CLIN APPL THROMB HEMOST
3: S64-S67
[Abstract]
Hull, R. D., Pineo, G. F.
(1997). Overview of Treatment of Venous Thromboembolism Based on Levels of Evidence. CLIN APPL THROMB HEMOST
3: S68-S71
The Columbus Investigators,
(1997). Low-Molecular-Weight Heparin in the Treatment of Patients with Venous Thromboembolism. NEJM
337: 657-662
[Abstract][Full Text]
Eby, C.
(1997). Standardization of APTT Reagents for Heparin Therapy Monitoring: Urgent or Fading Priority?. Clin. Chem.
43: 1105-1107
[Full Text]
Hull, R. D., Raskob, G. E., Rosenbloom, D., Pineo, G. F., Lerner, R. G., Gafni, A., Trowbridge, A. A., Elliott, C. G., Green, D., Feinglass, J., Feldstein, W., Brant, R.
(1997). Treatment of Proximal Vein Thrombosis With Subcutaneous Low-Molecular-Weight Heparin vs Intravenous Heparin: An Economic Perspective. Arch Intern Med
157: 289-294
[Abstract]
Ginsberg, J. S.
(1996). Management of Venous Thromboembolism. NEJM
335: 1816-1829
[Full Text]
Anand, S., Ginsberg, J. S., Kearon, C., Gent, M., Hirsh, J.
(1996). The Relation Between the Activated Partial Thromboplastin Time Response and Recurrence in Patients With Venous Thrombosis Treated With Continuous Intravenous Heparin. Arch Intern Med
156: 1677-1681
[Abstract]
Hirsh, J., Hoak, J.
(1996). Management of Deep Vein Thrombosis and Pulmonary Embolism : A Statement for Healthcare Professionals From the Council on Thrombosis (in Consultation With the Council on Cardiovascular Radiology), American Heart Association. Circulation
93: 2212-2245
[Full Text]
Levine, M., Gent, M., Hirsh, J., Leclerc, J., Anderson, D., Weitz, J., Ginsberg, J., Turpie, A. G., Demers, C., Kovacs, M., Geerts, W., Kassis, J., Desjardins, L., Cusson, J., Cruickshank, M., Powers, P., Brien, W., Haley, S., Willan, A.
(1996). A Comparison of Low-Molecular-Weight Heparin Administered Primarily at Home with Unfractionated Heparin Administered in the Hospital for Proximal Deep-Vein Thrombosis. NEJM
334: 677-681
[Abstract][Full Text]
Koopman, M. M.W., Prandoni, P., Piovella, F., Ockelford, P. A., Brandjes, D. P.M., van der Meer, J., Gallus, A. S., Simonneau, G., Chesterman, C. H., Prins, M. H., Bossuyt, P. M.M., de Haes, H., van den Belt, A. G.M., Sagnard, L., d'Azemar, P., Buller, H. R., The Tasman Study Group,
(1996). Treatment of Venous Thrombosis with Intravenous Unfractionated Heparin Administered in the Hospital as Compared with Subcutaneous Low-Molecular-Weight Heparin Administered at Home. NEJM
334: 682-687
[Abstract][Full Text]
Schafer, A. I.
(1996). Low-Molecular-Weight Heparin -- An Opportunity for Home Treatment of Venous Thrombosis. NEJM
334: 724-726
[Full Text]
Biemond, B. J., Friederich, P. W., Levi, M., Vlasuk, G. P., Buller, H. R., ten Cate, J. W.
(1996). Comparison of Sustained Antithrombotic Effects of Inhibitors of Thrombin and Factor Xa in Experimental Thrombosis. Circulation
93: 153-160
[Abstract][Full Text]
Hull, R. D., Raskob, G. E., Pineo, G. F., Brant, R. F.
(1995). The Low-Probability Lung Scan: A Need for Change in Nomenclature. Arch Intern Med
155: 1845-1851
[Abstract]
Hirsh, J.
(1995). The Optimal Duration of Anticoagulant Therapy for Venous Thrombosis. NEJM
332: 1710-1712
[Full Text]
Lensing, A. W. A., Prins, M. H., Davidson, B. L., Hirsh, J.
(1995). Treatment of Deep Venous Thrombosis With Low-Molecular-Weight Heparins: A Meta-analysis. Arch Intern Med
155: 601-607
[Abstract]
Weinmann, E. E., Salzman, E. W.
(1994). Deep-Vein Thrombosis. NEJM
331: 1630-1641
[Full Text]
Leizorovicz, A, Simonneau, G, Decousus, H, Boissel, J P
(1994). Comparison of efficacy and safety of low molecular weight heparins and unfractionated heparin in initial treatment of deep venous thrombosis: a meta-analysis. BMJ
309: 299-304
[Abstract][Full Text]
Elliott, C. G., Hiltunen, S. J., Suchyta, M., Hull, R. D., Raskob, G. E., Pineo, G. F., Jensen, R. L., Yeates, S., Kitterman, N.
(1994). Physician-Guided Treatment Compared With a Heparin Protocol for Deep Vein Thrombosis. Arch Intern Med
154: 999-1004
[Abstract]
Hull, R. D., Raskob, G. E., Ginsberg, J. S., Panju, A. A., Brill-Edwards, P., Coates, G., Pineo, G. F.
(1994). A Noninvasive Strategy for the Treatment of Patients With Suspected Pulmonary Embolism. Arch Intern Med
154: 289-297
[Abstract]
(1992). HEPARIN IS NEEDED FOR INITIAL TREATMENT OF DVT. JWatch General
1992: 7-7
[Full Text]
Previous
