Low-molecular-weight heparins and unfractionated heparin in the treatment of patients with acute venous thromboembolism: Results of a meta-analysis

Siragusa, Sergio; Cosmi, Benilde; Piovella, Franco; Hirsh, Jack; Ginsberg, Jeffrey S.

doi:10.1016/s0002-9343(97)89484-3

Cited by 364 publications

(218 citation statements)

References 42 publications

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“…With regard to recommendations for short-term LMWH versus short-term unfractionated heparin followed by VKA, the 2013 CPGs were based on several meta-analyses [27][28][29][30][31][32][33][34][35] of subgroups of patients with cancer comparing short-term LMWH, unfractionated heparin, or fondaparinux in the initial treatment of VTE in the general population. Since our previous recommendations, two metaanalyses 36,37 have compared short-term LMWH with unfractionated heparin in patients with cancer.…”

Section: Guideline Recommendations For the Treatment Of Established Vtementioning

confidence: 99%

International clinical practice guidelines including guidance for direct oral anticoagulants in the treatment and prophylaxis of venous thromboembolism in patients with cancer

Farge

Bounameaux

Brenner

et al. 2016

The Lancet Oncology

390

434

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Venous thromboembolism (VTE) is the second leading cause of death in patients with cancer. These patients are at an increased risk of developing VTE and are more likely to have a recurrence of VTE and bleeding while taking anticoagulants. Management of VTE in patients with cancer is a major therapeutic challenge and remains suboptimal worldwide. In 2013, the International Initiative on Thrombosis and Cancer (ITAC-CME), established to reduce the global burden of VTE in patients with cancer, published international guidelines for the treatment and prophylaxis of VTE and central venous catheter-associated thrombosis. The rapid global adoption of direct oral anticoagulants for management of VTE in patients with cancer is an emerging treatment trend that needs to be addressed based on the current level of evidence. In this Review, we provide an update of the ITAC-CME consensus recommendations based on a systematic review of the literature ranked according to the Grading of Recommendations Assessment, Development, and Evaluation scale. These guidelines aim to address in-hospital and outpatient cancer-associated VTE in specifi c subgroups of patients with cancer.

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Section: Guideline Recommendations For the Treatment Of Established Vtementioning

confidence: 99%

International clinical practice guidelines including guidance for direct oral anticoagulants in the treatment and prophylaxis of venous thromboembolism in patients with cancer

Farge

Bounameaux

Brenner

et al. 2016

The Lancet Oncology

390

434

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“…We also hand searched the conference proceedings of the American Society of Clinical Oncology (ASCO) (starting with its first volume in 1982) and of the American Society of Hematology (ASH) (starting with its 2003 issue). We reviewed the reference lists of included articles, relevant articles, and related systematic reviews [5][6][7][8][9][10] and used the related article feature in PubMed to identify additional articles.…”

Section: Data Sources and Searchesmentioning

confidence: 99%

Anticoagulation for the initial treatment of venous thromboembolism in patients with cancer

Akl

Rohilla

Barba³

et al. 2008

Cancer

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BACKGROUND.The authors compared the relative efficacy and safety of low‐ molecular‐weight heparin (LMWH) and unfractionated heparin (UFH) for the initial treatment of venous thromboembolism (VTE) between patients with and without cancer.METHODS.By using Cochrane methodology for systematic reviews, separate meta‐analyses were conducted for subgroups of patients with and without cancer, and relative risks (RRs) were compared for statistical significance. The methodologic quality for each outcome was assessed by using the Grading of Recommendations Assessment, Development, and Evaluation approach.RESULTS.LMWH reduced mortality significantly compared with UFH in patients with cancer (RR of 0.71; 95% confidence interval [95% CI], 0.52‐0.98 [moderate‐quality evidence]) but not in patients without cancer (RR of 0.97; 95% CI, 0.65‐1.46 [low‐quality evidence]). However, the difference in the RR for the 2 subgroups did not reach statistical significance (P = .113). The difference between LMWH and UFH in the effect on recurrent VTE was not statistically significant in the subgroup with cancer (RR of 0.78; 95% CI, 0.29‐2.08 [low‐quality evidence]), in the subgroup without cancer (RR of 0.94; 95% CI, 0.60‐1.46 [low‐quality evidence]), or between the 2 subgroups (P = .367). No data were available for bleeding outcomes, thrombocytopenia, or postphlebitic syndrome.CONCLUSIONS.The current results indicated that LMWH most likely is superior to UFH in reducing mortality in the initial treatment of VTE for patients with cancer. There is a need for more and better designed trials to confirm these findings. Cancer 2008. © 2008 American Cancer Society.

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“…Two recent meta-analyses evaluating randomized controlled trials of LMWHs versus unfractionated heparin have found a significant risk reduction in mortality rates in the LMWH arm. 6,7 Because the cytotoxic effects of LMWHs have not been reported, the effects on endothelial cells and vascularity may explain slower tumor growth. Prospective randomized trials are currently under way to evaluate effects on survival.…”

Section: Khorana Et Al Heparin Molecular Weight and Endothelial Cellsmentioning

confidence: 99%

Heparin Inhibition of Endothelial Cell Proliferation and Organization Is Dependent on Molecular Weight

Khorana

Sahni

Altland

et al. 2003

ATVB

133

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Objective-Studies have shown improved survival in cancer patients treated with low molecular weight heparins (LMWHs). Tumors depend on an expanding vasculature, and heparins may affect vessel growth and function. We investigated the effect of heparins differing in M r on selected endothelial cell properties. Methods and Results-Human umbilical vein endothelial cells were cultured with fibroblast growth factor-2 and heparins differing in M r . Cell proliferation was assessed by [ 3 H]thymidine incorporation, and vascular organization was assessed by in vitro assays. Maximum inhibition of 94Ϯ2% was observed with 6-kDa LMWH, greater than the inhibition seen with unfractionated heparin (58Ϯ8%) or 3-kDa LMWH (60Ϯ9%, Pϭ0.02 for both). No inhibition of proliferation was observed with heparin tetrasaccharide, octasaccharide, or pentasaccharide (fondaparinux). Three-and 6-kDa fractions decreased endothelial tube formation in Matrigel to 58Ϯ15% and 67Ϯ9% (PϽ0.05), respectively, of that with fibroblast growth factor-2, whereas no inhibition was observed with unfractionated heparin, tetrasaccharide, pentasaccharide, or octasaccharide. LMWH (6 kDa) also inhibited vessel formation in a placental explant. Conclusions-Heparin inhibition of endothelial cell proliferation and organization requires a chain length of Ͼ8 saccharide units, with maximal inhibition at M r of 6 kDa. This M r dependence differs from that required for anticoagulant activity. Key Words: low molecular weight heparins Ⅲ cancer Ⅲ angiogenesis Ⅲ endothelium Ⅲ thrombosis U nfractionated heparin is a heterogeneous mixture of polysaccharide molecules with a mean M r between 12 and 15 kDa containing glycosaminoglycan chains from 200 to 300 saccharide units. 1 Low molecular weight heparins (LMWHs) are fragments of unfractionated heparin produced by controlled enzymatic or chemical depolymerization with lower mean M r between 3 and 6 kDa and chain lengths of 12 to 18 saccharide units. 2 These structural differences result in important functional and pharmacokinetic differences, inasmuch as LMWHs have an increased anti-Xa/anti-IIa activity ratio, reduced plasma protein binding, decreased interaction with platelets and platelet factor 4, a prolonged half-life, and increased bioavailability after subcutaneous administration. 2,3 These changes give LMWHs an improved therapeutic profile compared with unfractionated heparin and have led to their increasing use in the treatment of venous and arterial thrombosis. See page 1954Individual studies 4,5 and meta-analyses 6,7 have found significant improvements in 3-and 6-month mortality in patients with cancer who were treated with LMWHs compared with unfractionated heparin. This survival advantage was found in subgroups differing in age, sex, and primary site of malignancy and could not be attributed to differences in thrombosis or bleeding complications. 8 The mechanism of this effect remains unknown but appears to be independent of the anticoagulant action of LMWH and may be related to effects on the vasculature. Prior studie...

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Low-molecular-weight heparins and unfractionated heparin in the treatment of patients with acute venous thromboembolism: Results of a meta-analysis

Cited by 364 publications

References 42 publications

International clinical practice guidelines including guidance for direct oral anticoagulants in the treatment and prophylaxis of venous thromboembolism in patients with cancer

International clinical practice guidelines including guidance for direct oral anticoagulants in the treatment and prophylaxis of venous thromboembolism in patients with cancer

Anticoagulation for the initial treatment of venous thromboembolism in patients with cancer

Heparin Inhibition of Endothelial Cell Proliferation and Organization Is Dependent on Molecular Weight

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