Anticoagulation for the long term treatment of venous thromboembolism in patients with cancer

Elie Akl, M. Barba, S. Rohilla, I. Terrenato, F. Sperati, P. Muti, H. J. Schünemann

Research output: Contribution to journalArticle

88 Citations (Scopus)

Abstract

Background: Cancer increases the risk of thromboembolic events and the risk of recurrent thromboembolic events while on anticoagulation. Objectives: To compare the efficacy and safety of low molecular weight heparin (LMWH) and oral anticoagulants (vitamin K antagonist (VKA) and ximelagatran) for the long term treatment of venous thromboembolism (VTE) in patients with cancer. Search strategy: A comprehensive search was undertaken including a January 2007 search of electronic databases; Cochrane Central Register of Controlled Trials (CENTRAL), (The Cochrane Library 2007, Issue 1). MEDLINE (1966 onwards; accessed via OVID), EMBASE (1980 onwards; accessed via OVID) and ISI the Web of Science. Hand search of the proceedings of the American Society of Clinical Oncology and of the American Society of Hematology. Checking of references of included studies, relevant papers and related systematic reviews. Use of "related article" feature in PubMed; and (5) search of ISI the Web of Science for papers citing landmark studies. Selection criteria: Randomized controlled trials (RCTs) comparing long term treatment with LMWH versus oral anticoagulants (VKA or ximelagatran) in patients with cancer and symptomatic objectively confirmed VTE. Data collection and analysis: Using a standardized data form we extracted data on methodological quality, participants, interventions and outcomes of interest: survival, recurrent VTE, major bleeding, minor bleeding, thrombocytopenia and postphlebitic syndrome. Main results: Of 3986 identified citations, eight RCTs were eligible and reported data for patients with cancer. Their overall methodological quality was moderate. Meta-analysis of six RCTs showed that 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 VTE (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). One RCT compared tinzaparin and dalteparin and showed no differences in the outcomes of interest. One RCT compared a six months extension of anticoagulation with 18 months Ximelagatran 24mg twice daily versus placebo. It showed a reduction in VTE (HR = 0.16; 95% CI 0.09 to 0.30) with no apparent effect on survival or bleeding. Authors' conclusions: For the long term treatment of VTE in patients with cancer, LMWH compared to VKA reduces venous thromboembolic events but not death. The decision for a patient with cancer and VTE to start long term LMWH versus oral anticoagulation should balance the benefits and downsides and integrate the patient's values and preferences for the important outcomes and alternative management strategies.

Original languageEnglish
Article numberCD006650
JournalThe Cochrane database of systematic reviews
Issue number2
DOIs
Publication statusPublished - 2008

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Venous Thromboembolism
Low Molecular Weight Heparin
Vitamin K
Randomized Controlled Trials
Confidence Intervals
Neoplasms
Hemorrhage
Thrombocytopenia
Anticoagulants
Therapeutics
Survival
Postphlebitic Syndrome
Dalteparin
Patient Preference
PubMed
MEDLINE
Patient Selection
Libraries
Meta-Analysis
Placebos

ASJC Scopus subject areas

  • Medicine(all)
  • Pharmacology (medical)

Cite this

Anticoagulation for the long term treatment of venous thromboembolism in patients with cancer. / Akl, Elie; Barba, M.; Rohilla, S.; Terrenato, I.; Sperati, F.; Muti, P.; Schünemann, H. J.

In: The Cochrane database of systematic reviews, No. 2, CD006650, 2008.

Research output: Contribution to journalArticle

Akl, Elie ; Barba, M. ; Rohilla, S. ; Terrenato, I. ; Sperati, F. ; Muti, P. ; Schünemann, H. J. / Anticoagulation for the long term treatment of venous thromboembolism in patients with cancer. In: The Cochrane database of systematic reviews. 2008 ; No. 2.
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abstract = "Background: Cancer increases the risk of thromboembolic events and the risk of recurrent thromboembolic events while on anticoagulation. Objectives: To compare the efficacy and safety of low molecular weight heparin (LMWH) and oral anticoagulants (vitamin K antagonist (VKA) and ximelagatran) for the long term treatment of venous thromboembolism (VTE) in patients with cancer. Search strategy: A comprehensive search was undertaken including a January 2007 search of electronic databases; Cochrane Central Register of Controlled Trials (CENTRAL), (The Cochrane Library 2007, Issue 1). MEDLINE (1966 onwards; accessed via OVID), EMBASE (1980 onwards; accessed via OVID) and ISI the Web of Science. Hand search of the proceedings of the American Society of Clinical Oncology and of the American Society of Hematology. Checking of references of included studies, relevant papers and related systematic reviews. Use of {"}related article{"} feature in PubMed; and (5) search of ISI the Web of Science for papers citing landmark studies. Selection criteria: Randomized controlled trials (RCTs) comparing long term treatment with LMWH versus oral anticoagulants (VKA or ximelagatran) in patients with cancer and symptomatic objectively confirmed VTE. Data collection and analysis: Using a standardized data form we extracted data on methodological quality, participants, interventions and outcomes of interest: survival, recurrent VTE, major bleeding, minor bleeding, thrombocytopenia and postphlebitic syndrome. Main results: Of 3986 identified citations, eight RCTs were eligible and reported data for patients with cancer. Their overall methodological quality was moderate. Meta-analysis of six RCTs showed that 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 VTE (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). One RCT compared tinzaparin and dalteparin and showed no differences in the outcomes of interest. One RCT compared a six months extension of anticoagulation with 18 months Ximelagatran 24mg twice daily versus placebo. It showed a reduction in VTE (HR = 0.16; 95{\%} CI 0.09 to 0.30) with no apparent effect on survival or bleeding. Authors' conclusions: For the long term treatment of VTE in patients with cancer, LMWH compared to VKA reduces venous thromboembolic events but not death. The decision for a patient with cancer and VTE to start long term LMWH versus oral anticoagulation should balance the benefits and downsides and integrate the patient's values and preferences for the important outcomes and alternative management strategies.",
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AU - Muti, P.

AU - Schünemann, H. J.

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N2 - Background: Cancer increases the risk of thromboembolic events and the risk of recurrent thromboembolic events while on anticoagulation. Objectives: To compare the efficacy and safety of low molecular weight heparin (LMWH) and oral anticoagulants (vitamin K antagonist (VKA) and ximelagatran) for the long term treatment of venous thromboembolism (VTE) in patients with cancer. Search strategy: A comprehensive search was undertaken including a January 2007 search of electronic databases; Cochrane Central Register of Controlled Trials (CENTRAL), (The Cochrane Library 2007, Issue 1). MEDLINE (1966 onwards; accessed via OVID), EMBASE (1980 onwards; accessed via OVID) and ISI the Web of Science. Hand search of the proceedings of the American Society of Clinical Oncology and of the American Society of Hematology. Checking of references of included studies, relevant papers and related systematic reviews. Use of "related article" feature in PubMed; and (5) search of ISI the Web of Science for papers citing landmark studies. Selection criteria: Randomized controlled trials (RCTs) comparing long term treatment with LMWH versus oral anticoagulants (VKA or ximelagatran) in patients with cancer and symptomatic objectively confirmed VTE. Data collection and analysis: Using a standardized data form we extracted data on methodological quality, participants, interventions and outcomes of interest: survival, recurrent VTE, major bleeding, minor bleeding, thrombocytopenia and postphlebitic syndrome. Main results: Of 3986 identified citations, eight RCTs were eligible and reported data for patients with cancer. Their overall methodological quality was moderate. Meta-analysis of six RCTs showed that 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 VTE (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). One RCT compared tinzaparin and dalteparin and showed no differences in the outcomes of interest. One RCT compared a six months extension of anticoagulation with 18 months Ximelagatran 24mg twice daily versus placebo. It showed a reduction in VTE (HR = 0.16; 95% CI 0.09 to 0.30) with no apparent effect on survival or bleeding. Authors' conclusions: For the long term treatment of VTE in patients with cancer, LMWH compared to VKA reduces venous thromboembolic events but not death. The decision for a patient with cancer and VTE to start long term LMWH versus oral anticoagulation should balance the benefits and downsides and integrate the patient's values and preferences for the important outcomes and alternative management strategies.

AB - Background: Cancer increases the risk of thromboembolic events and the risk of recurrent thromboembolic events while on anticoagulation. Objectives: To compare the efficacy and safety of low molecular weight heparin (LMWH) and oral anticoagulants (vitamin K antagonist (VKA) and ximelagatran) for the long term treatment of venous thromboembolism (VTE) in patients with cancer. Search strategy: A comprehensive search was undertaken including a January 2007 search of electronic databases; Cochrane Central Register of Controlled Trials (CENTRAL), (The Cochrane Library 2007, Issue 1). MEDLINE (1966 onwards; accessed via OVID), EMBASE (1980 onwards; accessed via OVID) and ISI the Web of Science. Hand search of the proceedings of the American Society of Clinical Oncology and of the American Society of Hematology. Checking of references of included studies, relevant papers and related systematic reviews. Use of "related article" feature in PubMed; and (5) search of ISI the Web of Science for papers citing landmark studies. Selection criteria: Randomized controlled trials (RCTs) comparing long term treatment with LMWH versus oral anticoagulants (VKA or ximelagatran) in patients with cancer and symptomatic objectively confirmed VTE. Data collection and analysis: Using a standardized data form we extracted data on methodological quality, participants, interventions and outcomes of interest: survival, recurrent VTE, major bleeding, minor bleeding, thrombocytopenia and postphlebitic syndrome. Main results: Of 3986 identified citations, eight RCTs were eligible and reported data for patients with cancer. Their overall methodological quality was moderate. Meta-analysis of six RCTs showed that 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 VTE (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). One RCT compared tinzaparin and dalteparin and showed no differences in the outcomes of interest. One RCT compared a six months extension of anticoagulation with 18 months Ximelagatran 24mg twice daily versus placebo. It showed a reduction in VTE (HR = 0.16; 95% CI 0.09 to 0.30) with no apparent effect on survival or bleeding. Authors' conclusions: For the long term treatment of VTE in patients with cancer, LMWH compared to VKA reduces venous thromboembolic events but not death. The decision for a patient with cancer and VTE to start long term LMWH versus oral anticoagulation should balance the benefits and downsides and integrate the patient's values and preferences for the important outcomes and alternative management strategies.

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