Blood thinners for the long-term treatment of blood clots in patients with cancer

Akl EA, Labedi N, Barba M, Terrenato I, Sperati F, Muti P, Schünemann H

Published Online:

June 15, 2011

Patients with cancer are at an increased risk of developing blood clots and might respond differently to blood thinners compared with patients without cancer. This systematic review compares the effects of long-term treatment with different blood thinners on blood clot recurrence in patients with cancer. Low molecular weight heparins (injectable blood thinners) are superior to vitamin K antagonists (oral blood thinners) in reducing the recurrence of blood clots. The available data suggest that both drugs have equal effects on death and the adverse event of bleeding. We were not able to include a number of possibly relevant studies because the required data were not available.

Abstract (click to read)

Background:

Cancer increases the risk of thromboembolic events even while on anticoagulation.

Objectives:

To compare the efficacy and safety of low molecular weight heparin (LMWH) and oral anticoagulants for the long-term treatment of venous thromboembolism (VTE) in patients with cancer.

Search strategy:

A comprehensive search for studies of anticoagulation in cancer patients including a February 2010 electronic search of: the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and ISI Web of Science.

Selection criteria:

Randomized controlled trials (RCTs) comparing long-term treatment with LMWH versus oral anticoagulants (vitamin K antagonist (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. We assessed the quality of evidence at the outcome level following the GRADE approach.

Main results:

Of 8187 identified citations, nine RCTs were eligible and reported data for 1908 patients with cancer. Meta-analysis of seven RCTs showed that LMWH, compared to VKA provided no statistically significant survival benefit (hazard ratio (HR) 0.96; 95% confidence interval (CI) 0.81 to 1.14) but a statistically significant reduction in VTE (HR 0.47; 95% CI 0.32 to 0.71). Other results did not exclude a beneficial or harmful effect of LMWH compared to VKA for the outcomes of major bleeding (RR 1.05; 95% CI 0.53 to 2.10) or thrombocytopenia (RR 1.02; 95% CI 0.60 to 1.74). The quality of evidence was low for mortality, major bleeding and minor bleeding and moderate for recurrent VTE. One RCT comparing six months extension of anticoagulation with 18 months ximelagatran 24 mg twice daily versus placebo found a reduction in VTE (HR 0.16; 95% CI 0.09 to 0.30) but did not exclude beneficial or harmful effects for the outcomes of mortality and bleeding. One RCT, comparing dabigatran to VKA, did not exclude beneficial or harmful effect of one agent over the other.

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.

This record should be cited as:

Akl EA, Labedi N, Barba M, Terrenato I, Sperati F, Muti P, Schünemann H. Anticoagulation for the long-term treatment of venous thromboembolism in patients with cancer. Cochrane Database of Systematic Reviews 2011, Issue 6. Art. No.: CD006650. DOI: 10.1002/14651858.CD006650.pub3

Assessed as up to date:

May 9, 2011

Find the research

Get full text at The Cochrane Library

Primary Review Group:

Gynaecological Cancer Group

PEARLS - Practical Evidence About Real Life Situations (click to read)

Clinical question:

How effective and safe are low molecular weight heparin (LMWH) and anticoagulants such as vitamin K antagonists (VKA) for the long term treatment of venous thromboembolism (VTE) in patients with cancer?

Bottom line:

For the long term treatment (up to 6 months) of VTE in patients with cancer, LMWH compared to VKA reduces venous thromboembolic events but not death. Both drugs have equal effects on death and the adverse risk of bleeding and thrombocytopenia.The decision to start long term LMWH versus oral anticoagulation for a patient with cancer and VTE should balance the benefits and downsides and integrate the patient’s values and preferences for the important outcomes and alternative management strategies.

Caveat:

The authors were unable to include a number of possibly relevant studies because the required data were not available.While LMWH decreases the incidence of VTE, it might be more costly and less acceptable because of the subcutaneous route of administration.

Context:

The presence of cancer increases the risk of VTE four to six-fold.¹ Patients with cancer might also respond differently to anticoagulants compared with patients without cancer. LMWH is given by injection, whereas VKA is given orally. 1. Heit J A et al. Arch Intern Med 2000;160:809–815.

Cochrane Systematic Review:

Akl EA et al. Anticoagulation for the long term treatment of thromboembolism in patients with cancer. Cochrane Reviews 2008, Issue 1. Article No. CD006650. DOI: 10.1002/14651858.CD006650.pub2. This review contains 8 studies involving 3986 participants.

Authored by:

Brian R McAvoy

Cochrane Primary Health Care Field

Health topics:

Cancer > Generic cancer care > Thrombo-embolism prevention & treatment

Cochrane Summaries^beta

Independent high-quality evidence for health care decision making

Blood thinners for the long-term treatment of blood clots in patients with cancer

More like this

Copyright © 2011 - The Cochrane Collaboration