Anticoagulation for the long term treatment of venous thromboembolism in patients with cancer.
BACKGROUND
Cancer increases the risk of thromboembolic events and the risk of recurrent thromboembolic events while on anticoagulation.


OBJECTIVE
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.


METHODS
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.


METHODS
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.


METHODS
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.


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.


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.
Akl
E A
EA
State University of New York at Buffalo, Department of Medicine, ECMC, CC-142, 462 Girder Street, Buffalo, New York 14215, USA. elieakl@buffalo.edu
Barba
M
M
Rohilla
S
S
Terrenato
I
I
Sperati
F
F
Muti
P
P
Schünemann
H J
HJ
D000925:Anticoagulants / Q000627:therapeutic use*; D001384:Azetidines / Q000627:therapeutic use; D001596:Benzylamines / Q000627:therapeutic use; D006495:Heparin, Low-Molecular-Weight / Q000627:therapeutic use; D006801:Humans; D009369:Neoplasms / Q000150:complications*; D016032:Randomized Controlled Trials as Topic; D054556:Venous Thromboembolism / Q000188:drug therapy*; D014812:Vitamin K / Q000037:antagonists & inhibitors
D000925:Anticoagulants; D001384:Azetidines; D001596:Benzylamines; D006495:Heparin, Low-Molecular-Weight; D014812:Vitamin K; C426686:ximelagatran