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      Low-molecular-weight heparins are superior to vitamin K antagonists for the long term treatment of venous thromboembolism in patients with cancer: a cochrane systematic review

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          Abstract

          Background

          Cancer and its therapies increase the risk of venous thromboembolism. Compared to patients without cancer, patients with cancer anticoagulated for venous thromboembolism are more likely to develop recurrent thrombotic events and major bleeding. Addressing all important outcomes including harm is of great importance to make evidence based health care decisions. The objective of this study was to compare low molecular weight heparin (LMWH) and oral anticoagulants (vitamin K antagonist (VKA) and ximelagatran) for the long term treatment of venous thromboembolism in patients with cancer.

          Methods

          A systematic review of the medical literature. We followed the Cochrane Collaboration methodology for conducting systematic reviews. We assessed methodological quality for each outcome by grading the quality of evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology.

          Results

          Eight randomized controlled trials (RCTs) were eligible and reported data for patients with cancer. The quality of evidence was low for death and moderate for recurrent venous thromboembolism. LMWH, compared to VKA provided no statistically significant survival benefit (Hazard ratio (HR) = 0.96; 95% CI 0.81 to 1.14) but a statistically significant reduction in venous thromboembolism (HR = 0.47; 95% (Confidence Interval (CI) = 0.32 to 0.71). There was no statistically significant difference between LMWH and VKA in bleeding outcomes (RR = 0.91; 95% CI = 0.64 to 1.31) or thrombocytopenia (RR = 1.02; 95% CI = 0.60 to 1.74).

          Conclusion

          For the long term treatment of venous thromboembolism in patients with cancer, LMWH compared to VKA reduces venous thromboembolism but not death.

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          Most cited references36

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          Extracting summary statistics to perform meta-analyses of the published literature for survival endpoints.

          Meta-analyses aim to provide a full and comprehensive summary of related studies which have addressed a similar question. When the studies involve time to event (survival-type) data the most appropriate statistics to use are the log hazard ratio and its variance. However, these are not always explicitly presented for each study. In this paper a number of methods of extracting estimates of these statistics in a variety of situations are presented. Use of these methods should improve the efficiency and reliability of meta-analyses of the published literature with survival-type endpoints.
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            Low-molecular-weight heparin versus a coumarin for the prevention of recurrent venous thromboembolism in patients with cancer.

            Patients with cancer have a substantial risk of recurrent thrombosis despite the use of oral anticoagulant therapy. We compared the efficacy of a low-molecular-weight heparin with that of an oral anticoagulant agent in preventing recurrent thrombosis in patients with cancer. Patients with cancer who had acute, symptomatic proximal deep-vein thrombosis, pulmonary embolism, or both were randomly assigned to receive low-molecular-weight heparin (dalteparin) at a dose of 200 IU per kilogram of body weight subcutaneously once daily for five to seven days and a coumarin derivative for six months (target international normalized ratio, 2.5) or dalteparin alone for six months (200 IU per kilogram once daily for one month, followed by a daily dose of approximately 150 IU per kilogram for five months). During the six-month study period, 27 of 336 patients in the dalteparin group had recurrent venous thromboembolism, as compared with 53 of 336 patients in the oral-anticoagulant group (hazard ratio, 0.48; P=0.002). The probability of recurrent thromboembolism at six months was 17 percent in the oral-anticoagulant group and 9 percent in the dalteparin group. No significant difference between the dalteparin group and the oral-anticoagulant group was detected in the rate of major bleeding (6 percent and 4 percent, respectively) or any bleeding (14 percent and 19 percent, respectively). The mortality rate at six months was 39 percent in the dalteparin group and 41 percent in the oral-anticoagulant group. In patients with cancer and acute venous thromboembolism, dalteparin was more effective than an oral anticoagulant in reducing the risk of recurrent thromboembolism without increasing the risk of bleeding. Copyright 2003 Massachusetts Medical Society
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              Prognosis of cancers associated with venous thromboembolism.

              Little is known about the prognosis of cancer discovered during or after an episode of venous thromboembolism. We linked the Danish National Registry of Patients, the Danish Cancer Registry, and the Danish Mortality Files to obtain data on the survival of patients who received a diagnosis of cancer at the same time as or after an episode of venous thromboembolism. Their survival was compared with that of patients with cancer who did not have venous thromboembolism (control patients), who were matched in terms of type of cancer, age, sex, and year of diagnosis. Of 668 patients who had cancer at the time of an episode of deep venous thromboembolism, 44.0 percent of those with data on the spread of disease (563 patients) had distant metastasis, as compared with 35.1 percent of 5371 control patients with data on spread (prevalence ratio, 1.26; 95 percent confidence interval, 1.13 to 1.40). In the group with cancer at the time of venous thromboembolism, the one-year survival rate was 12 percent, as compared with 36 percent in the control group (P<0.001), and the mortality ratio for the entire follow-up period was 2.20 (95 percent confidence interval, 2.05 to 2.40). Patients in whom cancer was diagnosed within one year after an episode of venous thromboembolism had a slightly increased risk of distant metastasis at the time of the diagnosis (prevalence ratio, 1.23 [95 percent confidence interval, 1.08 to 1.40]) and a relatively low rate of survival at one year (38 percent, vs. 47 percent in the control group; P<0.001). Cancer diagnosed at the same time as or within one year after an episode of venous thromboembolism is associated with an advanced stage of cancer and a poor prognosis.
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                Author and article information

                Journal
                J Exp Clin Cancer Res
                Journal of Experimental & Clinical Cancer Research : CR
                BioMed Central
                0392-9078
                1756-9966
                2008
                18 July 2008
                : 27
                : 1
                : 21
                Affiliations
                [1 ]Department of Medicine, State University of New York at Buffalo, Buffalo, NY, USA
                [2 ]Department of Epidemiology, Italian National Cancer Institute Regina Elena, Rome, Italy
                [3 ]Department of Medicine, Maulana Azad Medical College, University Of Delhi, New Delhi, India
                Article
                1756-9966-27-21
                10.1186/1756-9966-27-21
                2507703
                18634550
                14db2ef6-61c2-43eb-a5b4-af663e13c38d
                Copyright © 2008 Akl et al; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 29 May 2008
                : 18 July 2008
                Categories
                Research

                Oncology & Radiotherapy
                Oncology & Radiotherapy

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