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Meta-Analysis
. 2017 Feb 9;2(2):CD001100.
doi: 10.1002/14651858.CD001100.pub4.

Fixed dose subcutaneous low molecular weight heparins versus adjusted dose unfractionated heparin for the initial treatment of venous thromboembolism

Lindsay Robertson  1 , Lauren E Jones  1
Affiliations
Meta-Analysis

Fixed dose subcutaneous low molecular weight heparins versus adjusted dose unfractionated heparin for the initial treatment of venous thromboembolism

Lindsay Robertson et al. Cochrane Database Syst Rev. .

Abstract

Background: Low molecular weight heparins (LMWHs) have been shown to be effective and safe in preventing venous thromboembolism (VTE). They may also be effective for the initial treatment of VTE. This is the third update of the Cochrane Review first published in 1999.

Objectives: To evaluate the efficacy and safety of fixed dose subcutaneous low molecular weight heparin compared to adjusted dose unfractionated heparin (intravenous or subcutaneous) for the initial treatment of people with venous thromboembolism (acute deep venous thrombosis or pulmonary embolism).

Search methods: For this update the Cochrane Vascular Information Specialist (CIS) searched the Cochrane Vascular Specialised Register (15 September 2016). In addition the CIS searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 8) in the Cochrane Library (searched 15 September 2016) and trials' registries.

Selection criteria: Randomised controlled trials comparing fixed dose subcutaneous LMWH with adjusted dose intravenous or subcutaneous unfractionated heparin (UFH) in people with VTE.

Data collection and analysis: Two review authors independently selected trials for inclusion, assessed for quality and extracted data.

Main results: Six studies were added to this update resulting in a total of 29 included studies (n = 10,390). The quality of the studies was downgraded as there was a risk of bias in some individual studies relating to risk of attrition and reporting bias; in addition several studies did not adequately report on the randomisation methods used nor on how the treatment allocation was concealed.During the initial treatment period, the incidence of recurrent venous thromboembolic events was lower in participants treated with LMWH than in participants treated with UFH (Peto odds ratio (OR) 0.69, 95% confidence intervals (CI) 0.49 to 0.98; 6238 participants; 18 studies; P = 0.04; moderate-quality evidence). After a follow-up of three months, the period in most of the studies for which oral anticoagulant therapy was given, the incidence of recurrent VTE was lower in participants treated with LMWH than in participants with UFH (Peto OR 0.71, 95% CI 0.56 to 0.90; 6661 participants; 16 studies; P = 0.005; moderate-quality evidence). Furthermore, at the end of follow-up, LMWH was associated with a lower rate of recurrent VTE than UFH (Peto OR 0.72, 95% CI 0.59 to 0.88; 9489 participants; 22 studies; P = 0.001; moderate-quality evidence). LMWH was also associated with a reduction in thrombus size compared to UFH (Peto OR 0.71, 95% CI 0.61 to 0.82; 2909 participants; 16 studies; P < 0.00001; low-quality evidence), but there was moderate heterogeneity (I² = 56%). Major haemorrhages occurred less frequently in participants treated with LMWH than in those treated with UFH (Peto OR 0.69, 95% CI 0.50 to 0.95; 8780 participants; 25 studies; P = 0.02; moderate-quality evidence). There was no difference in overall mortality between participants treated with LMWH and those treated with UFH (Peto OR 0.84, 95% CI 0.70 to 1.01; 9663 participants; 24 studies; P = 0.07; moderate-quality evidence).

Authors' conclusions: This review presents moderate-quality evidence that fixed dose LMWH reduced the incidence of recurrent thrombotic complications and occurrence of major haemorrhage during initial treatment; and low-quality evidence that fixed dose LMWH reduced thrombus size when compared to UFH for the initial treatment of VTE. There was no difference in overall mortality between participants treated with LMWH and those treated with UFH (moderate-quality evidence). The quality of the evidence was assessed using GRADE criteria and downgraded due to concerns over risk of bias in individual trials together with a lack of reporting on the randomisation and concealment of treatment allocation methods used. The quality of the evidence for reduction of thrombus size was further downgraded because of heterogeneity between studies.

PubMed Disclaimer

Conflict of interest statement

LR: none known. LJ: none known.

Figures

1
1
Study flow diagram.
2
2
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
3
3
Funnel plot of comparison: 1 LMWH versus UFH in people with venous thromboembolism, outcome: 1.1 Incidence of recurrent venous thromboembolism during initial treatment.
4
4
Funnel plot of comparison: 1 LMWH versus UFH in people with venous thromboembolism, outcome: 1.4 Incidence of recurrent venous thromboembolism at 3 months' follow‐up.
5
5
Funnel plot of comparison: 1 LMWH versus UFH in people with venous thromboembolism, outcome: 1.6 Reduction in thrombus size (pre‐ and post‐treatment venograms).
1.1
1.1. Analysis
Comparison 1 LMWH versus UFH in patients with venous thromboembolism, Outcome 1 Incidence of recurrent venous thromboembolism during initial treatment.
1.2
1.2. Analysis
Comparison 1 LMWH versus UFH in patients with venous thromboembolism, Outcome 2 Incidence of recurrent venous thromboembolism at the end of follow‐up.
1.3
1.3. Analysis
Comparison 1 LMWH versus UFH in patients with venous thromboembolism, Outcome 3 Incidence of recurrent venous thromboembolism at 1 month follow‐up.
1.4
1.4. Analysis
Comparison 1 LMWH versus UFH in patients with venous thromboembolism, Outcome 4 Incidence of recurrent venous thromboembolism at 3 months' follow‐up.
1.5
1.5. Analysis
Comparison 1 LMWH versus UFH in patients with venous thromboembolism, Outcome 5 Incidence of recurrent venous thromboembolism at 6 months' follow‐up.
1.6
1.6. Analysis
Comparison 1 LMWH versus UFH in patients with venous thromboembolism, Outcome 6 Reduction in thrombus size (pre‐ and post‐treatment venograms).
1.7
1.7. Analysis
Comparison 1 LMWH versus UFH in patients with venous thromboembolism, Outcome 7 Incidence of major haemorrhagic episodes (during initial treatment).
1.8
1.8. Analysis
Comparison 1 LMWH versus UFH in patients with venous thromboembolism, Outcome 8 Overall mortality at the end of follow‐up.
2.1
2.1. Analysis
Comparison 2 LMWH versus UFH in patients with proximal deep venous thrombosis, Outcome 1 Incidence of recurrent venous thromboembolism at the end of follow‐up.
2.2
2.2. Analysis
Comparison 2 LMWH versus UFH in patients with proximal deep venous thrombosis, Outcome 2 Incidence of recurrent deep venous thrombosis at the end of follow‐up.
2.3
2.3. Analysis
Comparison 2 LMWH versus UFH in patients with proximal deep venous thrombosis, Outcome 3 Incidence of pulmonary embolism at the end of follow‐up.
2.4
2.4. Analysis
Comparison 2 LMWH versus UFH in patients with proximal deep venous thrombosis, Outcome 4 Reduction in thrombus size (pre‐ and post‐treatment venograms).
2.5
2.5. Analysis
Comparison 2 LMWH versus UFH in patients with proximal deep venous thrombosis, Outcome 5 Incidence of major haemorrhagic episodes (during initial treatment).
2.6
2.6. Analysis
Comparison 2 LMWH versus UFH in patients with proximal deep venous thrombosis, Outcome 6 Overall mortality at the end of follow‐up.
3.1
3.1. Analysis
Comparison 3 LMWH versus UFH in patients with pulmonary embolism, Outcome 1 Incidence of recurrent venous thromboembolism at the end of follow‐up.
3.2
3.2. Analysis
Comparison 3 LMWH versus UFH in patients with pulmonary embolism, Outcome 2 Reduction in thrombus size (pre‐ and post‐treatment venograms).
3.3
3.3. Analysis
Comparison 3 LMWH versus UFH in patients with pulmonary embolism, Outcome 3 Mean change in pulmonary vascular obstruction severity score.
3.4
3.4. Analysis
Comparison 3 LMWH versus UFH in patients with pulmonary embolism, Outcome 4 Incidence of major haemorrhagic episodes (during initial treatment).
3.5
3.5. Analysis
Comparison 3 LMWH versus UFH in patients with pulmonary embolism, Outcome 5 Overall mortality at end of follow‐up.
4.1
4.1. Analysis
Comparison 4 LMWH versus UFH in patients with venous thromboembolism and malignant disease, Outcome 1 Mortality at the end of follow‐up.
5.1
5.1. Analysis
Comparison 5 LMWH versus UFH in patients with venous thromboembolism without malignant disease, Outcome 1 Mortality at the end of follow‐up.
6.1
6.1. Analysis
Comparison 6 LMWH versus subcutaneous UFH in patients with venous thromboembolism, Outcome 1 Incidence of recurrent venous thromboembolism at the end of follow‐up.
6.2
6.2. Analysis
Comparison 6 LMWH versus subcutaneous UFH in patients with venous thromboembolism, Outcome 2 Incidence of major haemorrhagic episodes (during initial treatment).
6.3
6.3. Analysis
Comparison 6 LMWH versus subcutaneous UFH in patients with venous thromboembolism, Outcome 3 Overall mortality at the end of follow‐up.
7.1
7.1. Analysis
Comparison 7 LMWH versus intravenous UFH in patients with venous thromboembolism, Outcome 1 Incidence of recurrent venous thromboembolism at the end of follow‐up.
7.2
7.2. Analysis
Comparison 7 LMWH versus intravenous UFH in patients with venous thromboembolism, Outcome 2 Incidence of major haemorrhagic episodes (during initial treatment).
7.3
7.3. Analysis
Comparison 7 LMWH versus intravenous UFH in patients with venous thromboembolism, Outcome 3 Overall mortality at the end of follow‐up.
8.1
8.1. Analysis
Comparison 8 LMWH versus UFH: all randomised controlled trials with adequate concealment of allocation, Outcome 1 Incidence of recurrent venous thromboembolism during initial treatment.
8.2
8.2. Analysis
Comparison 8 LMWH versus UFH: all randomised controlled trials with adequate concealment of allocation, Outcome 2 Incidence of recurrent venous thromboembolism at the end of follow‐up.
8.3
8.3. Analysis
Comparison 8 LMWH versus UFH: all randomised controlled trials with adequate concealment of allocation, Outcome 3 Incidence of recurrent venous thromboembolism at 3 months' follow‐up.
8.4
8.4. Analysis
Comparison 8 LMWH versus UFH: all randomised controlled trials with adequate concealment of allocation, Outcome 4 Reduction in thrombus size (pre‐ and post‐treatment venograms).
8.5
8.5. Analysis
Comparison 8 LMWH versus UFH: all randomised controlled trials with adequate concealment of allocation, Outcome 5 Incidence of major haemorrhagic episodes (during initial treatment).
8.6
8.6. Analysis
Comparison 8 LMWH versus UFH: all randomised controlled trials with adequate concealment of allocation, Outcome 6 Overall mortality at the end of follow‐up.
9.1
9.1. Analysis
Comparison 9 LMWH versus UFH: all randomised controlled trials that used ISTH definition of major bleeding, Outcome 1 Incidence of major haemorrhagic episodes (during initial treatment).
10.1
10.1. Analysis
Comparison 10 LMWH versus UFH by year of publication, Outcome 1 Incidence of recurrent venous thromboembolism during initial treatment.
10.2
10.2. Analysis
Comparison 10 LMWH versus UFH by year of publication, Outcome 2 Incidence of recurrent venous thromboembolism at the end of follow‐up.
10.3
10.3. Analysis
Comparison 10 LMWH versus UFH by year of publication, Outcome 3 Incidence of major haemorrhagic episodes (during initial treatment).
10.4
10.4. Analysis
Comparison 10 LMWH versus UFH by year of publication, Outcome 4 Overall mortality at the end of follow‐up.
See this image and copyright information in PMC

Update of

References

References to studies included in this review

Belcaro 1999 {published data only}
    1. Belcaro G, Nicolaides AN, Cesarone MR, Laurora G, Sanctis MT, Incandela L, et al. 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 1999;50(10):781‐7. - PubMed
Breddin 2001 {published data only}
    1. Breddin HK, Hach‐Wunderle V, Nakov R, Kakkar VV. Effects of a low‐molecular‐weight heparin on thrombus regression and recurrent thromboembolism in patients with deep‐vein thrombosis. New England Journal of Medicine 2001;344(9):626‐31. - PubMed
Columbus 1997 {published data only}
    1. Douketis JD, Foster GA, Crowther MA, Prins MH, Ginsberg JS. Clinical risk factors and timing of recurrent venous thromboembolism during the initial 3 months of anticoagulant therapy. Archives of Internal Medicine 2000;160(22):3431‐6. - PubMed
    1. The Columbus Investigators. Low molecular weight heparin is an effective and safe treatment for deep‐vein thrombosis and pulmonary embolism. Blood 1996; Vol. 88:626a.
    1. The Columbus Investigators. Low‐molecular‐weight heparin in the treatment of patients with venous thromboembolism. New England Journal of Medicine 1997;337(10):657‐62. - PubMed
    1. Cate JW, Büller HR, Gent M, Gallus AS, Ginsberg J, Prins MH, et al. Low‐molecular‐weight heparin in the treatment of patients with venous thromboembolism. Journal of Vascular and Interventional Radiology 1998;9:178.
Decousus 1998 {published data only}
    1. Decousus H, Leizorovicz A, Parent F, Page Y, Tardy B, Girard PH, et al. A clinical trial of vena cava filters in the prevention of pulmonary embolism in patients with proximal deep‐vein thrombosis. New England Journal of Medicine 1998;338(7):409‐15. - PubMed
Faivre 1988 {published data only}
    1. Faivre R, Neuhart E, Kieffer Y, Toulemonde F, Bassand JP, Maurat JP. Subcutaneous administration of a low molecular weight heparin (CY 222) compared with subcutaneous administration of standard heparin in patients with acute deep vein thrombosis. Thrombosis and Haemostasis 1987;58(1):Abstract 430.
    1. Faivre R, Neuhart Y, Kieffer Y, Apfel F, Magnin D, Didier D, et al. A new treatment of deep vein thrombosis: low molecular weight heparin fractions. Randomised study [Un nouveau traitement des thromboses veineuses profondes: les fractions d'heparine de bas poids moleculaire. Etude randomisee]. Presse Medicale 1988;17(5):197‐200. - PubMed
Fiessinger 1996 {published data only}
    1. Fiessinger JN, Fernandez ML, Gatterer E, Ohlsson CG. Fragmin once daily versus continuous infusion heparin in the treatment of DVT: a European multicentre trial. Haemostasis 1994;24(Suppl 1):Abstract 44.
    1. Fiessinger JN, Lopez‐Fernandez M, Gatterer E, Granqvist S, Kher A, Olsson CG, et al. Once‐daily subcutaneous dalteparin, a low molecular weight heparin, for the initial treatment of acute deep vein thrombosis. Thrombosis and Haemostasis 1996;76(2):195‐9. - PubMed
Findik 2002 {published data only}
    1. Findik S, Erkan ML, Selçuk MB, Albayrak S, Atici AG, Doru F. Low‐molecular‐weight heparin versus unfractionated heparin in the treatment of patients with acute pulmonary thromboembolism. Respiration 2002;69(5):440‐4. - PubMed
Goldhaber 1998 {published data only}
    1. Goldhaber SZ, Morrison RB, Diran LL, Creager MA, Lee TH Jr. Abbreviated hospitalization for deep venous thrombosis with the use of ardeparin. Archives of Internal Medicine 1998;158(21):2325‐8. - PubMed
Harenberg 2000a {published data only}
    1. Harenberg J, Schmidt JA, Koppenhagen K, Tolle A, Huisman MV, Buller HR. Fixed‐dose, body weight‐independent subcutaneous LMW heparin versus adjusted dose unfractionated intravenous heparin in the initial treatment of proximal venous thrombosis. EASTERN Investigators. Thrombosis and Haemostasis 2000;83(5):652‐6. - PubMed
Hull 1992 {published data only}
    1. Hull RD, Raskob GE, Brant RF, Pineo GF, Elliott G, Stein PD, et al. Low‐molecular‐weight heparin vs heparin in the treatment of patients with pulmonary embolism. American‐Canadian Thrombosis Study Group. Archives of Internal Medicine 2000;160(2):229‐36. - PubMed
    1. Hull RD, Raskob GE, Pineo GF, Green D, Trowbridge AA, Elliott CG, et al. Subcutaneous low‐molecular‐weight heparin compared with continuous intravenous heparin in the treatment of proximal‐vein thrombosis. New England Journal of Medicine 1992;326(15):975‐82. - PubMed
Kakkar 2003 {published data only}
    1. Kakkar VV, Gebska M, Kadziola Z, Saba N, Carrasco P, Bemiparin Investigators. Low‐molecular‐weight heparin in the acute and long‐term treatment of deep vein thrombosis. Thrombosis and Haemostasis 2003;89(4):674‐80. - PubMed
Kirchmaier 1998 {published data only}
    1. Kirchmaier CM, Wolf H, Schafer H, Ehlers B, Breddin HK. Efficacy of a low molecular weight heparin administered intravenously or subcutaneously in comparison with intravenous unfractionated heparin in the treatment of deep venous thrombosis. Certoparin‐Study Group. International Angiology 1998;17(3):135‐45. - PubMed
Koopman 1996 {published data only}
    1. Koopman MMW, Prandoni P, Piovella F, Ockelford PA, Brandjes DPM, Meer J, et al. Treatment of venous thrombosis with intravenous unfractionated heparin administered in the hospital as compared with subcutaneous low‐molecular‐weight heparin administered at home. New England Journal of Medicine 1996;334(11):682‐7. - PubMed
Leizorovicz 2011 {published data only}
    1. Leizorovicz A. Tinzaparin compared to unfractionated heparin for initial treatment of deep vein thrombosis in very elderly patients with renal insufficiency ‐ the IRIS trial. Blood 2008; Vol. 112, issue 11:434.
    1. Leizorovicz A, Siguret V, Mottier D. Safety profile of tinzaparin versus subcutaneous unfractionated heparin in elderly patients with impaired renal function treated for acute deep vein thrombosis: The Innohep((R)) in Renal Insufficiency Study (IRIS). Thrombosis Research 2011;128(1):27‐34. - PubMed
    1. NCT00277394. Innohep© in elderly patients with impaired renal function treated for acute deep vein thrombosis. clinicaltrials.gov/ct/show/NCT00277394 2007.
    1. Siguret V, Deudon C, Golmard J, Leizorovicz A, Pautas E, Gouin‐Thibault I. Pharmacodynamic response to unfractionated heparin used for initial treatment of acute deep vein thrombosis in elderly patients with renal impairment. A substudy of the IRIS clinical trial. Journal of Thrombosis and Haemostasis 2013;11 (Suppl 2):805.
Levine 1996 {published data only}
    1. Levine M, Gent M, Hirsh J, Leclerc J, Anderson D, Weitz J, et al. A comparison of low‐molecular‐weight heparin administered primarily at home with unfractionated heparin administered in the hospital for proximal deep‐vein thrombosis. New England Journal of Medicine 1996;334(11):677‐81. - PubMed
Lindmarker 1994 {published data only}
    1. Holmstrom M, Lindmarker P, Granqvist S, Johnsson H, Lockner D. A 6‐month venographic follow‐up in 164 patients with acute deep vein thrombosis. Thrombosis and Haemostasis 1997;78(2):803‐7. - PubMed
    1. Lindmarker P, Holmstrom M, Granqvist S, Johnsson H, Lockner D. Comparison of once‐daily subcutaneous Fragmin (TM) with continuous intravenous unfractionated heparin in the treatment of deep venous thrombosis. Thrombosis and Haemostasis 1994;72(2):186‐90. - PubMed
Lopaciuk 1992 {published data only}
    1. Lopaciuk S, Meissner AJ, Filipecki S, Zawilska K, Sowier J, Ciesielski L, et al. Subcutaneous low molecular weight heparin versus subcutaneous unfractionated heparin in the treatment of deep vein thrombosis: a Polish multicenter trial. Thrombosis and Haemostasis 1992;68(1):14‐8. - PubMed
Luomanmaki 1996 {published data only}
    1. Luomanmaki K and the Finnish Multicentre Group, et al. Low molecular weight heparin (Fragmin) once daily vs continuous infusion of standard heparin in the treatment of DVT. Haemostasis 1994;24(Suppl 1):Abstract 248.
    1. Luomanmaki K, Grankvist S, Hallert C, Jauro I, Ketola K, Kim HC, et al. A multicentre comparison of once‐daily subcutaneous dalteparin (low molecular weight heparin) and continuous intravenous heparin in the treatment of deep vein thrombosis. Journal of Internal Medicine 1996;240(2):85‐92. - PubMed
Merli 2001 {published data only}
    1. Merli G, Spiro TE, Olsson CG, 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. Annals of Internal Medicine 2001;134(3):191‐202. - PubMed
    1. Spiro TE, The Enoxaparin Clinical Trial Group. A multicenter clinical trial comparing once and twice‐daily subcutaneous enoxaparin and intravenous heparin in the treatment of acute deep vein thrombosis. Thrombosis and Haemostasis 1997;374(Suppl):Abstract SC 1527.
    1. Lissovoy G, Yusen RD, Spiro TE, Krupski WC, Champion AH, Sorensen SV. Cost for inpatient care of venous thrombosis: a trial of enoxaparin vs standard heparin. Archives of Internal Medicine 2000;160(20):3160‐5. - PubMed
Meyer 1995 {published data only}
    1. Meyer G, Brenot F, Pacouret G, Simonneau G, Gillet Juvin K, Charbonnier B, et al. Subcutaneous low‐molecular weight heparin Fragmin versus intravenous unfractionated heparin in the treatment of acute non massive pulmonary embolism: an open randomised pilot study. Thrombosis and Haemostasis 1995;74(6):1432‐5. - PubMed
Moreno‐Palomares 2001 {published data only}
    1. Moreno‐Palomares JJ, Fisac‐Herrero RM, Herrero Domingo A, Ferreira‐Pasos EM, Grasa J, Reverte Cejudo D. [Low molecular weight heparin versus unfractionated heparin in the treatment of deep vein thrombosis]. Anales de Medicina Interna 2001;18(7):364‐8. - PubMed
Ninet 1991 {published data only}
    1. Ninet J, Bachet P, Prandoni P, Ruol A, Vigo M, Barret A, et al. A randomized trial of subcutaneous low molecular weight heparin (CY216) compared with intravenous unfractionated heparin in the treatment of deep vein thrombosis. Thrombosis and Haemostasis 1991;65(3):251‐6. - PubMed
Pérez de Llano 2003 {published data only}
    1. Pérez de Llano LA, Baloira Villar A, Veres Racamonde A, Veiga F, Golpe, Gomez R, et al. Multicenter, prospective study comparing enoxaparin with unfractionated heparin in the treatment of submassive pulmonary thromboembolism. Archivos de Bronconeumologia 2003;39(8):341‐5. - PubMed
Prandoni 1992 {published data only}
    1. Prandoni P, Lensing AWA, Büller HR, Carta M, Cogo A, Vigo M, et al. Comparison of subcutaneous low‐molecular‐weight heparin with intravenous standard heparin in proximal deep‐vein thrombosis. Lancet 1992;339(8791):441‐5. - PubMed
Prandoni 2004 {published data only}
    1. Prandoni P, Carnovali M, Marchiori A. Subcutaneous adjusted‐dose unfractionated heparin vs fixed‐dose low‐molecular‐weight heparin in the initial treatment of venous thromboembolism. Archives of Internal Medicine 2004;164:1077‐83. - PubMed
Riess 2003 {published data only}
    1. Riess H, Koppenhagen K, Tolle A, Kemkes‐Matthes B, Grave M, Patek F, et al. Fixed‐dose, body weight‐independent subcutaneous low molecular weight heparin Certoparin compared with adjusted‐dose intravenous unfractionated heparin in patients with proximal deep venous thrombosis. Thrombosis and Haemostasis 2003;90(2):252‐9. - PubMed
    1. Riess H, Koppenhagen K, Tolle AR, Kemkes‐Matthes B, Grave M, Harenberg J, et al. Fixed‐dose body weight‐independent subcutaneous LMW‐heparin (LMWH) certoparin is equally effective to adjusted‐dose intravenous uf‐heparin (UFH) for the initial treatment of proximal deep venous thrombosis (DVT). Annals of Hematology 2001;80 Suppl 1:A56.
Simonneau 1993 {published data only}
    1. Simonneau G, Charbonnier B, Decousus H, Planchon B, Ninet J, Sie P, et al. Subcutaneous low molecular weight heparin compared with continuous intravenous unfractionated heparin in the initial treatment proximal vein thrombosis. Archives of Internal Medicine 1993;153(13):1541‐6. - PubMed
Simonneau 1997 {published data only}
    1. Simonneau G, Sors H, Charbonnier B, Page Y, Laaban J‐P, Azarian R, et al. for the THESEE Study Group. A comparison of low‐molecular‐weight heparin with unfractionated heparin for acute pulmonary embolism. New England Journal of Medicine 1997;337(10):663‐9. - PubMed
Thery 1992 {published data only}
    1. Thery C, Simonneau G, Meyer G, Helenon O, Bridey F, Armagnac C, et al. Randomized trial of subcutaneous low‐molecular‐weight heparin CY216 (fraxiparine) compared with intravenous unfractionated heparin in the curative treatment of submassive pulmonary embolism. Circulation 1992;85(4):1380‐9. - PubMed

References to studies excluded from this review

Aiach 1989 {published data only}
    1. Aiach M, Fiessinger JN, Vitoux JF, Querrec A, Gouault‐Heilmann M, et al. Deep vein thrombosis treatment. A comparative study: subcutaneous Fragmin versus unfractionated heparin administered by continuous infusion. Multicentre trial. [Traitement des thromboses veineuses profondes constituees. Etude comparative d'un fragment d'heparine de bas poids moleculaire (Fragmine) administree par voie sous‐cutanee et de l'heparine standard administree par voie intraveineuse continue. Etude multicentrique. [French]]. Revue de Medecine Interne 1989;10(4):375‐81. - PubMed
Albada 1989 {published data only}
    1. Albada J, Nieuwenhuis HK, Sixma JJ. Treatment of acute venous thromboembolism with low molecular weight heparin (Fragmin). Circulation 1989;80(4):935‐40. - PubMed
Banga 1993 {published data only}
    1. Banga JD, Valk HW, Wester JWJ, Brouwer CB, Hessen MWJ, Meuwissen OJAT, et al. A dose finding study of subcutaneous heparinoid Oragaran (ORG 10172) twice daily compared to continuous intravenous unfractionated heparin in the treatment of venous thromboembolism. Thrombosis and Haemostasis 1993;69:545 Abstract 20.
Bratt 1985 {published data only}
    1. Bratt G, Tornebohm E, Granqvist S, Aberg W, Lockner D. A comparison between low molecular weight heparin Kabi 2165 and standard heparin in the intravenous treatment of deep vein thrombosis. Thrombosis and Haemostasis 1985;54(4):813‐7. - PubMed
Bratt 1990 {published data only}
    1. Bratt G, Aberg W, Johansson M, Tornebohm E, Granqvist S, Lockner D. Two daily subcutaneous injections of Fragmin as compared with intravenous standard heparin in the treatment of deep venous thrombosis. Thrombosis and Haemostasis 1990;64(4):506‐10. - PubMed
de Valk 1995 {published data only}
    1. Valk HW, Banga JD, Wester JWJ, Brouwer CB, Hessen MWJ, Meuwissen OJAT, et al. Comparing subcutaneous danaparoid with intravenous unfractionated heparin for the treatment of venous thromboembolism. A randomised controlled trial. Annals of Internal Medicine 1995;123(1):1‐9. - PubMed
Handeland 1990 {published data only}
    1. Handeland GF, Abildgaard U, Holm HA, Arnesen KE. Dose adjusted heparin treatment of deep venous thrombosis: a comparison of unfractionated and low molecular weight heparin. European Journal of Clinical Pharmacology 1990;39(2):107‐12. - PubMed
Harenberg 1989 {published data only}
    1. Harenberg J, Huck K, Stehle G, Mall K, Schwarz A, Heene DL. Prospective randomized, controlled study on the treatment of deep venous thrombosis using low molecular weight heparin compared with unfractionated heparin. Thrombosis and Haemostasis 1989;62:356 Abstract No. 1106.
    1. Harenberg J, Huisman MV, Tolle AR, Breddin HK, Kirchmaier CM. Reduction in thrombus extension and clinical end points in patients after initial treatment for deep vein thrombosis with the fixed‐dose body weight‐independent low molecular weight heparin certoparin. Seminars in Thrombosis and Hemostasis 2001;27:513‐8. - PubMed
    1. Harenberg J, Riess H, Fischer H, Brom J, Eidinger GW. Initial treatment of patients with acute deep‐vein thrombosis using 8.000 IU bid low‐molecular‐weight heparin certoparin ‐ A 24 months follow up. Journal of Thrombosis and Haemostasis 2005;3(1):Abstract No. P1021.
Harenberg 1990 {published data only}
    1. Harenberg J, Huck K, Bratsch H, Stehle G, Dempfle CE, Mall K, et al. Therapeutic application of subcutaneous low‐molecular‐weight heparin in acute venous thrombosis. Haemostasis 1990;20 Suppl 1:205‐19. - PubMed
    1. Harenberg J, Stehle G, Blauth M, Huck K, Mall K, Heene DL. Dosage, anticoagulant and antithrombotic effects of heparin and low‐molecular‐weight heparin in the treatment of deep vein thrombosis. Seminars in Thrombosis and Hemostasis 1997;23(1):83‐90. - PubMed
Harenberg 2000b {published data only}
    1. Harenberg J, Breddin HK, Kirchmaier CM, Tolle A. Does fixed dose body weight independent subcutaneous low‐molecular‐weight heparin improve the Marder score compared to adjusted dose unfractionated heparin in the treatment of venous thrombosis. Annals of Hematology 2000;79 Suppl 1:A84.
Holm 1986 {published data only}
    1. Holm HA, Ly B, Handeland GF, Abildegaard U, Arnesen KE, Gottschalk P, et al. Subcutaneous heparin treatment of deep vein thrombosis: a comparison of unfractionated and low molecular weight heparin. Haemostasis 1986;16 Suppl 2:30‐7. - PubMed
Kearon 2006 {published data only}
    1. Kearon C, Ginsberg JJ, Julian J, Douketis J, Solymoss S, Ockelford P, et al. Fixed‐dose, weight‐adjusted, unfractionated heparin (UFH) given subcutaneously (sc) without laboratory monitoring for acute treatment of venous thromboembolism (VTE): Randomized comparison with low‐molecular‐weight‐heparin (LMWH). Blood 2004; Vol. 104, issue 11:Abstract 707.
    1. Kearon C, Ginsberg JS, Julian J, Douketis J, Solymoss S, Ockelford P, et al. Acute treatment of venous thromboembolism (VTE) with fixed‐dose, weight‐adjusted, unfractionated heparin (UFH) given subcutaneously (sc) without laboratory monitoring: randomized comparison with low‐molecular‐weight‐heparin (LMWH). Journal of Thrombosis and Haemostasis 2005; Vol. 3, issue 1:Abstract number: OR147.
    1. Kearon C, Ginsberg JS, Julian JA, Douketis J, Solymoss S, Ockelford P, et al. Comparison of fixed‐dose weight‐adjusted‐unfractionated heparin and low‐molecular weight heparin for acute treatment of venous thromboembolism. JAMA 2006;296:935‐42. - PubMed
Lockner 1985 {published data only}
    1. Lockner D, Bratt G, Tornebohm E, Aberg W, Granqvist S. A comparison between low molecular weight heparin (LMWH, KABI 2165) and standard heparin in the intravenous treatment of deep vein thrombosis (DVT). Thrombosis and Haemostasis 1985;54(4):813‐7. - PubMed
Lockner 1986 {published data only}
    1. Lockner D, Bratt G, Tornebohm E, Aberg W, Granqvist S. Intravenous and subcutaneous administration of Fragmin in deep venous thrombosis. Haemostasis 1986;16 Suppl 2:25‐9. - PubMed
Ly 1985 {published data only}
    1. Ly B, Arnesen KE, Holm HA, Handeland GF, Abilgaard U. Subcutaneous LMW or unfractionated heparin in DVT: A randomized, double blind study with dose adjustments according to heparin concentration in plasma. Thrombosis and Haemostasis 1985;54(1):Abstract No. 91.
Monreal 1993 {published data only}
    1. Monreal M, Lafoz E, Vedia C, Roncales J. Comparison of subcutaneous unfractioned heparin with a low molecular weight heparin (Fragmin) in patients with venous thromboembolism and contraindications to coumarin. Thrombosis and Haemostasis 1993;69(649):Abstract No. 383. - PubMed
Monreal 1994 {published data only}
    1. Monreal M, Lafoz E, Olive A, Rio L. Comparison of subcutaneous unfractioned heparin with a low molecular weight heparin (Fragmin) in patients with venous thromboembolism and contraindications to coumarin. Thrombosis and Haemostasis 1994;71(1):7‐11. - PubMed
Notarbartolo 1988 {published data only}
    1. Notarbartolo A, Salanitri G, Davi G, Averna M, Barbagallo C, Catalano I. Low molecular weight heparin in the short and long‐term treatment of deep vein thrombosis in diabetic subjects. Praxis Med 1988;9:393‐405.
Quiros 2001 {published data only}
    1. Quiros M. Use of heparin of low molecular weight in the ambulatory handling of patients with deep venous thrombosis. Comparative study: heparin nondivided versus low molecular weight heparin. Revista costarricense de cardiologia 2001;3(2):8‐13.
Riess 2014 {published data only}
    1. Riess H, Becker LK, Melzer N, Harenberg J. Treatment of deep vein thrombosis in patients with pulmonary embolism: Subgroup analysis on the efficacy and safety of certoparin vs. unfractionated heparin. Blood Coagulation & Fibrinolysis 2014;25(8):838‐44. - PubMed
Siguret 2011 {published data only}
    1. Siguret V, Gouin‐Thibault I, Pautas E, Leizorovicz A. No accumulation of the peak anti‐Xa activity of tinzaparin in elderly patients with moderate‐to‐severe renal impairment: the IRIS substudy. Journal of Thrombosis and Haemostasis 2011;9(10):1966‐72. - PubMed
Stricker 1999 {published data only}
    1. Stricker H, Marchetti O, Haeberli A, Mombelli G. Hemostatic activation under anticoagulant treatment: a comparison of unfractionated heparin vs. nadroparin in the treatment of proximal deep vein thrombosis. Thrombosis and Haemostasis 1999;82(4):1227‐31. - PubMed
Tedoldi 1993 {published data only}
    1. Tedoldi A, Botticella F, Maloberti MR. Antithrombophilic effect of low molecular weight heparins in patients with deep vein thrombosis. Clinical Trials and Meta‐analysis 1993;28(4‐5):215‐25.
Ucar 2015 {published data only}
    1. Ucar EY, Akgun M, Araz O, Tas H, Kerget B, Meral M, et al. Comparison of LMWH versus UFH for hemorrhage and hospital mortality in the treatment of acute massive pulmonary thromboembolism after thrombolytic treatment: randomized controlled parallel group study. Lung. Springer New York LLC, 2015; Vol. 193, issue 1:121‐7. - PubMed
Vogel 1987 {published data only}
    1. Vogel G, Machulik M. Efficacy and safety of a low molecular weight heparin (LMW‐heparin Sandoz) in patients with deep vein thrombosis. Thrombosis and Haemostasis 1987;58 Suppl:Abstract No. 427.
Zanghi 1988 {published data only}
    1. Zanghi M, Morici V, Costanzo M, Astuto L, Salanitri G. Deep vein thrombosis of the legs: new therapy by means of low molecular weight heparins. Journal of International Medical Research 1988;16(6):474‐84. - PubMed

References to ongoing studies

NCT00796692 {published data only}
    1. NCT00796692. Nadroparin for the initial treatment of pulmonary thromboembolism (NATSPUTE). ClinicalTrials.gov (first received 20 November 2008).

Additional references

Buller 1991
    1. Buller HR, Lensing AWA, Hirsh J, Cate JW. Deep venous thrombosis: new noninvasive tests. Thrombosis and Haemostasis 1991;66(1):133‐9. - PubMed
Collins 1987
    1. Collins R, Gray R, Godwin J, Peto R. Avoidance of large biases and large random errors in the assessment of moderate treatment effects: the need for systematic overviews. Statistics in Medicine 1987;6(3):245‐50. - PubMed
Deeks 2011
    1. Deeks JJ, Higgins JPT, Altman DG. Chapter 9: Analysing data and undertaking meta‐analyses. In: Higgins JPT, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 [updated March 2011]. The Cochrane Collaboration, 2011. Available from handbook.cochrane.org.
Diaz 2015
    1. Diaz JP, Soto Molina H, Marquez M, Escobar Juarez Y. Low‐molecular‐weight heparin in treatment of deep‐vein thrombosis: A network meta‐analysis. Value in Health 2015;18(3):A31.
GRADE Working Group 2008
    1. Guyatt GH, Oxman AD, Vist GE, et al. GRADE: an emerging consensus on rating quality of evidence and strength of recommendations. British Medical Journal 2008;336(7650):924‐6. - PMC - PubMed
Higgins 2011a
    1. Higgins JP, Green S, editor(s). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 (updated March 2011). The Cochrane Collaboration, 2011. Available from handbook.cochrane.org.
Higgins 2011b
    1. Higgins JPT, Altman DG, Sterne JAC, editor(s). Chapter 8: Assessing risk of bias in included studies. In: Higgins JPT, Green S, editor(s). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 (updated March 2011). The Cochrane Collaboration, 2011. Available from handbook.cochrane.org.
Hirsh 1990
    1. Hirsh J. From unfractionated heparins to low molecular weight heparins. Acta Chirurgica Scandinavica 1990;156 Suppl 556:42‐50. - PubMed
Hirsh 1992
    1. Hirsh J, Levine MN. Low molecular weight heparin. Blood 1992;79(1):1‐17. - PubMed
Huisman 1989
    1. Huisman MV, Buller HR, Cate JW, Royen EA, Vreeken J, Kersten MJ, et al. Unexpected high prevalence of silent pulmonary embolism in patients with deep vein thrombosis. Chest 1989;95(3):498‐502. - PubMed
Hull 1983
    1. Hull RD, Hirsh J, Carter CJ, Jay RM, Dodd PE, Ockelford PA, et al. Pulmonary angiography, ventilation lung scanning, and venography for suspected pulmonary embolism with abnormal perfusion lung scan. Annals of Internal Medicine 1983;98(6):891‐9. - PubMed
Kearon 2012
    1. Kearon C, Akl EA, Comerota AJ, Prandoni P, Bounameaux H, Goldhaber SZ, et al. Antithrombotic therapy for VTE disease: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians Evidence‐Based Clinical Practice Guidelines. Chest 2012;141(2 Suppl):e419S‐94S. - PMC - PubMed
Mantel 1959
    1. Mantel N, Haenszel W. Statistical aspects of the analysis of data from retrospective studies of disease. Journal of the National Cancer Institute 1959;22(4):719‐48. - PubMed
NICE 2012
    1. NICE. Venous thromboembolic diseases: diagnosis, management and thrombophilia testing. www.nice.org.uk/guidance/cg144 (accessed 15 November 2016).
Nurmohamed 1992
    1. Nurmohamed MT, Rosendaal FR, Buller HR, Dekker E, Hommes DW, Vandenbroucke JP, et al. Low‐molecular‐weight heparin versus standard heparin in general and orthopaedic surgery: a meta‐analysis. Lancet 1992;340(8812):152‐6. - PubMed
RevMan 2014 [Computer program]
    1. The Nordic Cochrane Centre, The Cochrane Collaboration. Review Manager (RevMan). Version 5.3. Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2014.
Schulman 2005
    1. Schulman S, Kearon C, and the Subcommittee on Control of Anticoagulation of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis. Definition of major bleeding in clinical investigations of antihemostatic medicinal products in non‐surgical patients. Journal of Thrombosis and Haemostasis 2005;3(4):692‐4. - PubMed
Sterne 2011
    1. Sterne JAC, Egger M, Moher D. Chapter 10: Addressing reporting biases. In: Higgins JPT, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions. Version 5.1.0 [updated March 2011]. The Cochrane Collaboration, 2011. Available from handbook.cochrane.org.
Turpie 2002
    1. Turpie AGG, Chin BSP, Lip GYH. Venous thromboembolism: treatment strategies. British Medical Journal 2002;325(7370):948‐50. - PMC - PubMed
van den Belt 1998
    1. Belt AGM, Bossuyt PMM, Prins MH, Gallus AS, Buller HR, Koopman MMW, et al. Replacing inpatient care by outpatient care in the treatment of deep venous thrombosis. An economic evaluation. Thrombosis and Haemostasis 1998;79(2):259‐63. - PubMed

References to other published versions of this review

Erkens 2010
    1. Erkens PMG, Prins MH. Fixed dose subcutaneous low molecular weight heparins versus adjusted dose unfractionated heparin for venous thromboembolism. Cochrane Database of Systematic Reviews 2010, Issue 9. [DOI: 10.1002/14651858.CD001100.pub3] - DOI - PubMed
van den Belt 1999
    1. Belt AGM, Prins MH, Lensing AWA, Castro AA, Clark OAC, Atallah AN, Burihan E. Fixed dose subcutaneous low molecular weight heparins versus adjusted dose unfractionated heparin for venous thromboembolism. Cochrane Database of Systematic Reviews 1999, Issue 4. [DOI: 10.1002/14651858.CD001100] - DOI - PubMed
van Dongen 2004
    1. Dongen CJ, Belt AGM, Prins MH, Lensing AWA. Fixed dose subcutaneous low molecular weight heparins versus adjusted dose unfractionated heparin for venous thromboembolism. Cochrane Database of Systematic Reviews 2004, Issue 4. [DOI: 10.1002/14651858.CD001100.pub2] - DOI - PubMed

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