We conducted a comprehensive search for studies of anticoagulation in
cancer patients including 1. a February 2013 electronic search of: the Cochrane Central Register of Controlled Trials (CENTRAL Issue 12, 2012), MEDLINE, and EMBASE; 2. a handsearch of conference proceedings; 3. checking of references of included studies; 4. use of the 'related citation' feature in PubMed; and 5. a search of clinicaltrials.gov for ongoing studies.
SELECTION CRITERIA: 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 9559 identified citations, 10 RCTs (11 reports) were eligible and reported data for 1981 patients with
cancer. We excluded 14 studies in which patients with
cancer constituted study subgroups, but did not report outcome data for them. Meta-analysis of seven RCTs comparing
LMWH with VKA found 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). The remaining findings did not exclude a beneficial or harmful effect of
LMWH compared with VKA for the outcomes of major
bleeding (RR 1.07; 95% CI 0.52 to 2.19), minor
bleeding (RR 0.89; 95% CI 0.51 to 1.55), or
thrombocytopenia (RR 0.98; 95% CI 0.57 to 1.66). We judged the quality of evidence as low for mortality, major
bleeding, and minor
bleeding, and as moderate for recurrent VTE.One RCT comparing
dabigatran with VKA did not exclude beneficial or harmful effects of one agent over the other. One RCT comparing six months' extension of anticoagulation with 18 months of
ximelagatran 24 mg twice daily versus no extended
ximelagatran did not exclude beneficial or harmful effects for the outcomes of reduction in VTE, mortality, and minor
bleeding. One RCT comparing once-weekly
subcutaneous injection of
idraparinux for three or six months versus standard treatment (parenteral anticoagulation followed by
warfarin or
acenocoumarol) suggested a reduction in recurrent VTE (HR 0.39; 95% CI 0.14 to 1.11) at six months, but did not exclude beneficial or harmful effects for the outcomes of mortality (HR 0.99; 95% CI 0.66 to 1.48) and major
bleeding (RR 1.04; 95% CI 0.39 to 2.83).
AUTHORS' CONCLUSIONS: For the long-term treatment of VTE in patients with
cancer,
LMWH compared with VKA reduces venous thromboembolic events but not mortality. The decision for a patient with
cancer and VTE to start long-term
LMWH versus oral anticoagulation should balance the benefits and harms and integrate the patient's values and preferences for the important outcomes and alternative management strategies.