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Published in: Thrombosis Journal 1/2011

Open Access 01-12-2011 | Original clinical investigation

Meta regression analysis to indirectly compare dalteparin to enoxaparin for the prevention of venous thromboembolic events following total hip replacement

Authors: George Dranitsaris, Valentina Jelincic, Yoonhee Choe

Published in: Thrombosis Journal | Issue 1/2011

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Abstract

Background

Patients undergoing elective total hip replacement (THR) surgery are at an increased risk for venous thromboembolic events (VTEs). Dalteparin and enoxaparin are recommended as thromboprophylaxis for at least 10 days in these patients. Even though both agents have proven clinical effectiveness through placebo controlled studies, there have been no head to head trials to assess comparative effectiveness. Indirect statistical techniques were used to compare safety and efficacy between dalteparin and enoxaparin following THR surgery.

Methods

A literature search was conducted from January 1980 to November 2009 for randomized trials evaluating dalteparin or enoxaparin prophylaxis in THR patients. In trials where a common control was used (e.g. placebo), indirect statistical comparisons between dalteparin and enoxaparin were performed using meta regression analysis with active drug as the primary independent variable.

Results

A total of nine placebo controlled enoxaparin (n = 5) and dalteparin (n = 4) trials met the inclusion criteria. THR patients treated with enoxaparin or dalteparin had a 50% VTE risk reduction compared to the placebo control (RR = 0.50, p < 0.001). This benefit was achieved without a significant increase in the risk for major bleeds (RR = 1.19, p = 0.76), heparin induced thrombocytopenia (HIT) (RR = 1.13, p = 0.83) or death (RR = 0.72, p = 0.59). The indirect comparison was not able to find significant differences between enoxaparin and dalteparin in terms of VTEs (p = 0.36), major bleeds (p = 0.45), HIT (p = 0.48) and death (p = 0.86).

Conclusions

The findings suggested comparable safety and efficacy between dalteparin and enoxaparin in TKR patients. Therefore, treatment decisions should be based on other considerations, such as patient or physician preference, ease of administration and cost.
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Literature
1.
go back to reference Weinmann EE, Salzman EW: Deep vein thrombosis. N Engl J Med 1994, 331: 1630-41. 10.1056/NEJM199412153312407CrossRefPubMed Weinmann EE, Salzman EW: Deep vein thrombosis. N Engl J Med 1994, 331: 1630-41. 10.1056/NEJM199412153312407CrossRefPubMed
2.
go back to reference Spyropoulos AC, Lin J: Direct medical costs of venous thromboembolism and subsequent hospital readmission rates: an administrative claims analysis from 30 managed care organizations. J Manag Care Pharm 2007, 13: 475-86.PubMed Spyropoulos AC, Lin J: Direct medical costs of venous thromboembolism and subsequent hospital readmission rates: an administrative claims analysis from 30 managed care organizations. J Manag Care Pharm 2007, 13: 475-86.PubMed
3.
go back to reference Landefeld CS, Ilanus P: Economic burden of venous thromboembolism. In Prevention of Venous Thrombosis. New York, NY: Marcel Dekker; 1993:69-85. Landefeld CS, Ilanus P: Economic burden of venous thromboembolism. In Prevention of Venous Thrombosis. New York, NY: Marcel Dekker; 1993:69-85.
4.
go back to reference Geerts WH, Bergqvist D, Pinei GF, et al.: Prevention of venous thromboembolism: the 8thEdition ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest 2008, 133: 381S-453S. 10.1378/chest.08-0656CrossRefPubMed Geerts WH, Bergqvist D, Pinei GF, et al.: Prevention of venous thromboembolism: the 8thEdition ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest 2008, 133: 381S-453S. 10.1378/chest.08-0656CrossRefPubMed
5.
go back to reference Kher A, Samama MM: Primary and secondary prophylaxis of venous thromboembolism with low-molecular-weight heparins: prolonged thromboprophylaxis, an alternative to vitamin K antagonists. J Thromb Haemost 2005, 3: 473-81. 10.1111/j.1538-7836.2005.01180.xCrossRefPubMed Kher A, Samama MM: Primary and secondary prophylaxis of venous thromboembolism with low-molecular-weight heparins: prolonged thromboprophylaxis, an alternative to vitamin K antagonists. J Thromb Haemost 2005, 3: 473-81. 10.1111/j.1538-7836.2005.01180.xCrossRefPubMed
6.
go back to reference Mills EJ, Rachlis B, O'Regan C, Thabane L, Perri D: Metastatic renal cell cancer treatments: an indirect comparison meta-analysis. BMC Cancer 2009, 27: 9-34. Mills EJ, Rachlis B, O'Regan C, Thabane L, Perri D: Metastatic renal cell cancer treatments: an indirect comparison meta-analysis. BMC Cancer 2009, 27: 9-34.
7.
go back to reference Dranitsaris G, Mehta S: Oral therapies for the treatment of pulmonary arterial hypertension: a population-based cost-minimization analysis. Appl Health Econ Health Policy 2009, 7: 43-59.CrossRefPubMed Dranitsaris G, Mehta S: Oral therapies for the treatment of pulmonary arterial hypertension: a population-based cost-minimization analysis. Appl Health Econ Health Policy 2009, 7: 43-59.CrossRefPubMed
8.
go back to reference DerSimonian R, Laird N: Meta-analysis in clinical trials. Controlled Clin Trials 1986, 7: 177-188. 10.1016/0197-2456(86)90046-2CrossRefPubMed DerSimonian R, Laird N: Meta-analysis in clinical trials. Controlled Clin Trials 1986, 7: 177-188. 10.1016/0197-2456(86)90046-2CrossRefPubMed
10.
go back to reference Begg CB, Mazumdar M: Operating characteristics of a rank correlation test for publication bias. Biometrics 1994, 50: 1088-101. 10.2307/2533446CrossRefPubMed Begg CB, Mazumdar M: Operating characteristics of a rank correlation test for publication bias. Biometrics 1994, 50: 1088-101. 10.2307/2533446CrossRefPubMed
12.
go back to reference Sutton AJ, Abrams , Jones , Sheldon TA, Song F: Systematic reviews of trials and other studies: Meta regression. Health Tech Assess 1998, 2: 81-84. Sutton AJ, Abrams , Jones , Sheldon TA, Song F: Systematic reviews of trials and other studies: Meta regression. Health Tech Assess 1998, 2: 81-84.
13.
go back to reference Bucher HC, Guyatt GH, Griffith LE, Walter SD: The results of direct and indirect treatment comparisons in meta-analysis of randomized controlled trials. J Clin Epidemiol 1997, 50: 683-691. 10.1016/S0895-4356(97)00049-8CrossRefPubMed Bucher HC, Guyatt GH, Griffith LE, Walter SD: The results of direct and indirect treatment comparisons in meta-analysis of randomized controlled trials. J Clin Epidemiol 1997, 50: 683-691. 10.1016/S0895-4356(97)00049-8CrossRefPubMed
14.
go back to reference Wells G, Sultan SA, Chen L, et al.: Indirect Evidence: Indirect Treatment Comparisons in Meta-Analysis. The Canadian Agency for Drugs and Technologies in Health (CADTH) Report; 2009. Wells G, Sultan SA, Chen L, et al.: Indirect Evidence: Indirect Treatment Comparisons in Meta-Analysis. The Canadian Agency for Drugs and Technologies in Health (CADTH) Report; 2009.
15.
go back to reference Song F, Altman DG, Glenny AM, Deeks JJ: Validity of indirect comparison for estimating efficacy of competing interventions: empirical evidence from published meta-analyses. BMJ 2003, 326: 472. 10.1136/bmj.326.7387.472PubMedCentralCrossRefPubMed Song F, Altman DG, Glenny AM, Deeks JJ: Validity of indirect comparison for estimating efficacy of competing interventions: empirical evidence from published meta-analyses. BMJ 2003, 326: 472. 10.1136/bmj.326.7387.472PubMedCentralCrossRefPubMed
16.
go back to reference Tørholm C, Broeng L, Jørgensen PS, et al.: Thromboprophylaxis by low-molecular-weight heparin in elective hip surgery. A placebo controlled study. J Bone Joint Surg Br 1991, 73: 434-438.PubMed Tørholm C, Broeng L, Jørgensen PS, et al.: Thromboprophylaxis by low-molecular-weight heparin in elective hip surgery. A placebo controlled study. J Bone Joint Surg Br 1991, 73: 434-438.PubMed
17.
go back to reference Dechavanne M, Ville D, Berruyer M, et al.: Randomized trial of a low-molecular-weight heparin (Kabi 2165) versus adjusted-dose subcutaneous standard heparin in the prophylaxis of deep-vein thrombosis after elective hip surgery. Haemostasis 1989, 19: 5-12.PubMed Dechavanne M, Ville D, Berruyer M, et al.: Randomized trial of a low-molecular-weight heparin (Kabi 2165) versus adjusted-dose subcutaneous standard heparin in the prophylaxis of deep-vein thrombosis after elective hip surgery. Haemostasis 1989, 19: 5-12.PubMed
18.
go back to reference McCart GM, Kayser SR: Therapeutic equivalency of low-molecular-weight heparins. Ann Pharmacother 2002, 36: 1042-1057. 10.1345/aph.10264CrossRefPubMed McCart GM, Kayser SR: Therapeutic equivalency of low-molecular-weight heparins. Ann Pharmacother 2002, 36: 1042-1057. 10.1345/aph.10264CrossRefPubMed
19.
go back to reference Dahl OE, Andreassen G, Aspelin T, et al.: Prolonged thromboprophylaxis following hip replacement surgery-results of a double-blind, prospective, randomised, placebo-controlled study with dalteparin (Fragmin). Thromb Haemost 1997, 77: 26-31.PubMed Dahl OE, Andreassen G, Aspelin T, et al.: Prolonged thromboprophylaxis following hip replacement surgery-results of a double-blind, prospective, randomised, placebo-controlled study with dalteparin (Fragmin). Thromb Haemost 1997, 77: 26-31.PubMed
20.
go back to reference Lassen MR, Borris LC, Anderson BS, et al.: Efficacy and safety of prolonged thromboprophylaxis with a low molecular weight heparin (dalteparin) after total hip arthroplasty. Thromb Res 1998, 89: 281-7. 10.1016/S0049-3848(98)00018-8CrossRefPubMed Lassen MR, Borris LC, Anderson BS, et al.: Efficacy and safety of prolonged thromboprophylaxis with a low molecular weight heparin (dalteparin) after total hip arthroplasty. Thromb Res 1998, 89: 281-7. 10.1016/S0049-3848(98)00018-8CrossRefPubMed
21.
go back to reference Hull RD, Pineo GF, Francis C, et al.: Low-molecular-weight heparin prophylaxis using dalteparin in close proximity to surgery vs. warfarin in hip arthroplasty patients: a double-blind, randomized comparison. The North American Fragmin Trial Investigators. Arch Intern Med 2000, 160: 2199-2207. 10.1001/archinte.160.14.2199CrossRefPubMed Hull RD, Pineo GF, Francis C, et al.: Low-molecular-weight heparin prophylaxis using dalteparin in close proximity to surgery vs. warfarin in hip arthroplasty patients: a double-blind, randomized comparison. The North American Fragmin Trial Investigators. Arch Intern Med 2000, 160: 2199-2207. 10.1001/archinte.160.14.2199CrossRefPubMed
22.
go back to reference Hull RD, Pineo GF, Francis C, et al.: Low-molecular-weight heparin prophylaxis using dalteparin extended out-of-hospital vs in-hospital warfarin/out-of-hospital placebo in hip arthroplasty patients: a double-blind, randomized comparison. North American Fragmin Trial Investigators. Arch Intern Med 2000, 160: 2208-2215. 10.1001/archinte.160.14.2208CrossRefPubMed Hull RD, Pineo GF, Francis C, et al.: Low-molecular-weight heparin prophylaxis using dalteparin extended out-of-hospital vs in-hospital warfarin/out-of-hospital placebo in hip arthroplasty patients: a double-blind, randomized comparison. North American Fragmin Trial Investigators. Arch Intern Med 2000, 160: 2208-2215. 10.1001/archinte.160.14.2208CrossRefPubMed
23.
go back to reference Turpie AG, Levine MN, Hirsh J, et al.: A randomized controlled trial of a low-molecular-weight heparin (enoxaparin) to prevent deep-vein thrombosis in patients undergoing elective hip surgery. N Engl J Med 1986, 315: 925-929. 10.1056/NEJM198610093151503CrossRefPubMed Turpie AG, Levine MN, Hirsh J, et al.: A randomized controlled trial of a low-molecular-weight heparin (enoxaparin) to prevent deep-vein thrombosis in patients undergoing elective hip surgery. N Engl J Med 1986, 315: 925-929. 10.1056/NEJM198610093151503CrossRefPubMed
24.
go back to reference Planes A, Vochelle N, Mazas F, et al.: Prevention of postoperative venous thrombosis: a randomized trial comparing unfractionated heparin with low molecular weight heparin in patients undergoing total hip replacement. Thromb Haemost 1988, 60: 407-410.PubMed Planes A, Vochelle N, Mazas F, et al.: Prevention of postoperative venous thrombosis: a randomized trial comparing unfractionated heparin with low molecular weight heparin in patients undergoing total hip replacement. Thromb Haemost 1988, 60: 407-410.PubMed
25.
go back to reference Levine MN, Hirsh J, Gent M, et al.: Prevention of deep vein thrombosis after elective hip surgery. A randomized trial comparing low molecular weight heparin with standard unfractionated heparin. Ann Intern Med 1991, 114: 545-551.CrossRefPubMed Levine MN, Hirsh J, Gent M, et al.: Prevention of deep vein thrombosis after elective hip surgery. A randomized trial comparing low molecular weight heparin with standard unfractionated heparin. Ann Intern Med 1991, 114: 545-551.CrossRefPubMed
26.
go back to reference Colwell CW Jr, Spiro TE, Trowbridge AA, et al.: Use of enoxaparin, a low-molecular-weight heparin, and unfractionated heparin for the prevention of deep venous thrombosis after elective hip replacement. A clinical trial comparing efficacy and safety. Enoxaparin Clinical Trial Group. J Bone Joint Surg Am 1994, 76: 3-14.PubMed Colwell CW Jr, Spiro TE, Trowbridge AA, et al.: Use of enoxaparin, a low-molecular-weight heparin, and unfractionated heparin for the prevention of deep venous thrombosis after elective hip replacement. A clinical trial comparing efficacy and safety. Enoxaparin Clinical Trial Group. J Bone Joint Surg Am 1994, 76: 3-14.PubMed
27.
go back to reference Avikainen V, von Bonsdorff H, Partio E, et al.: Low molecular weight heparin (enoxaparin) compared with unfractionated heparin in prophylaxis of deep venous thrombosis and pulmonary embolism in patients undergoing hip replacement. Ann Chir Gynaecol 1995, 84: 85-90.PubMed Avikainen V, von Bonsdorff H, Partio E, et al.: Low molecular weight heparin (enoxaparin) compared with unfractionated heparin in prophylaxis of deep venous thrombosis and pulmonary embolism in patients undergoing hip replacement. Ann Chir Gynaecol 1995, 84: 85-90.PubMed
28.
go back to reference Bergqvist D, Benoni G, Björgell O, et al.: Low-molecular-weight heparin (enoxaparin) as prophylaxis against venous thromboembolism after total hip replacement. N Engl J Med 1996, 335: 696-700. 10.1056/NEJM199609053351002CrossRefPubMed Bergqvist D, Benoni G, Björgell O, et al.: Low-molecular-weight heparin (enoxaparin) as prophylaxis against venous thromboembolism after total hip replacement. N Engl J Med 1996, 335: 696-700. 10.1056/NEJM199609053351002CrossRefPubMed
29.
go back to reference Planes A, Vochelle N, Darmon JY, et al.: Risk of deep-venous thrombosis after hospital discharge in patients having undergone total hip replacement: double-blind randomised comparison of enoxaparin versus placebo. Lancet 1996, 348: 224-228. 10.1016/S0140-6736(96)01453-5CrossRefPubMed Planes A, Vochelle N, Darmon JY, et al.: Risk of deep-venous thrombosis after hospital discharge in patients having undergone total hip replacement: double-blind randomised comparison of enoxaparin versus placebo. Lancet 1996, 348: 224-228. 10.1016/S0140-6736(96)01453-5CrossRefPubMed
30.
go back to reference Rader CP, Kramer C, König A, et al.: Low-molecular-weight heparin and partial thromboplastin time-adjusted unfractionated heparin in thromboprophylaxis after total knee and total hip arthroplasty. J Arthroplasty 1998, 13: 180-185. 10.1016/S0883-5403(98)90096-1CrossRefPubMed Rader CP, Kramer C, König A, et al.: Low-molecular-weight heparin and partial thromboplastin time-adjusted unfractionated heparin in thromboprophylaxis after total knee and total hip arthroplasty. J Arthroplasty 1998, 13: 180-185. 10.1016/S0883-5403(98)90096-1CrossRefPubMed
31.
go back to reference Comp PC, Spiro TE, Friedman RJ, et al.: Prolonged enoxaparin therapy to prevent venous thromboembolism after primary hip or knee replacement. Enoxaparin Clinical Trial Group. J Bone Joint Surg Am 2001, 83: 336-345.PubMed Comp PC, Spiro TE, Friedman RJ, et al.: Prolonged enoxaparin therapy to prevent venous thromboembolism after primary hip or knee replacement. Enoxaparin Clinical Trial Group. J Bone Joint Surg Am 2001, 83: 336-345.PubMed
32.
go back to reference Senaran H, Acaroğlu E, Ozdemir HM, et al.: Enoxaparin and heparin comparison of deep vein thrombosis prophylaxis in total hip replacement patients. Arch Orthop Trauma Surg 2006, 126: 1-5. 10.1007/s00402-005-0079-0CrossRefPubMed Senaran H, Acaroğlu E, Ozdemir HM, et al.: Enoxaparin and heparin comparison of deep vein thrombosis prophylaxis in total hip replacement patients. Arch Orthop Trauma Surg 2006, 126: 1-5. 10.1007/s00402-005-0079-0CrossRefPubMed
33.
go back to reference Fuji T, Ochi T, Niwa S, et al.: Prevention of postoperative venous thromboembolism in Japanese patients undergoing total hip or knee arthroplasty: two randomized double-blind placebo-controlled studies with three dosage regimens of enoxaparin. J Orthop Sci 2008, 13: 442-451. 10.1007/s00776-008-1264-0CrossRefPubMed Fuji T, Ochi T, Niwa S, et al.: Prevention of postoperative venous thromboembolism in Japanese patients undergoing total hip or knee arthroplasty: two randomized double-blind placebo-controlled studies with three dosage regimens of enoxaparin. J Orthop Sci 2008, 13: 442-451. 10.1007/s00776-008-1264-0CrossRefPubMed
Metadata
Title
Meta regression analysis to indirectly compare dalteparin to enoxaparin for the prevention of venous thromboembolic events following total hip replacement
Authors
George Dranitsaris
Valentina Jelincic
Yoonhee Choe
Publication date
01-12-2011
Publisher
BioMed Central
Published in
Thrombosis Journal / Issue 1/2011
Electronic ISSN: 1477-9560
DOI
https://doi.org/10.1186/1477-9560-9-3

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