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

Background

Patients with cancer are at an increased risk of developing blood clots and might respond differently to blood thinners (anticoagulants) compared with patients without cancer.

Study characteristics

We searched scientific databases for clinical trials looking at the effects of long-term treatment with different blood thinners on blood clot recurrence in people with cancer with a confirmed diagnosis of deep venous thrombosis (a blood clot in the legs) or pulmonary thrombosis (a blood clot in the lungs). We included trials of adults and children with either solid tumors or blood cancer irrespective of the type of cancer treatment. The trials looked at survival, recurrent blood clot, bleeding, blood platelet levels (which are involved in blood clotting), and postphlebitic syndrome (a complication of long-term blood clots). The evidence is current to February 2013.

Key results

We found 10 studies with 1981 patients with cancer. The studies found that low molecular weight heparins (injectable blood thinners) were superior to vitamin K antagonists (oral blood thinners) in reducing the recurrence of blood clots. The available data suggested that both drugs have equal effects on death and the side effect of bleeding.

Quality of the evidence

We were unable to include several possibly relevant studies because the required data were not available. We judged the quality of the evidence for recurrence of blood clots as moderate and the quality of the evidence as low for death and bleeding.

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.

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Background: 

Cancer increases the risk of thromboembolic events in patients including those receiving anticoagulation treatments.

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: 

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: 

We included 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 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).

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