Primary prophylaxis for venous thromboembolism in ambulatory cancer patients receiving chemotherapy

BACKGROUND: Venous thromboembolism (VTE) often complicates the clinical course of
cancer disease. The risk is further increased by chemotherapy but the safety and
efficacy of primary thromboprophylaxis in cancer patients treated with
chemotherapy is uncertain.
OBJECTIVES: To assess the efficacy and safety of primary thromboprophylaxis in
ambulatory cancer patients receiving chemotherapy.
SEARCH METHODS: The Cochrane Peripheral Vascular Diseases Group searched their
Specialised Register (last searched 3 May 2011) and CENTRAL (2011, Issue 2). The
authors searched clinical trials registries and reference lists of relevant
studies.
SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing unfractionated
heparin (UFH), low molecular weight heparin (LMWH), vitamin K antagonists (VKA),
direct thrombin inhibitors, direct factor Xa inhibitors or mechanical
intervention to no intervention or placebo; or comparing two different
anticoagulants.
DATA COLLECTION AND ANALYSIS: Data were extracted on methodological quality,
patients, interventions and outcomes including symptomatic VTE and major bleeding
as the primary effectiveness and safety outcomes, respectively.
MAIN RESULTS: Nine RCTs with a total of 3538 patients were considered. None of
the RCTs tested UFH, fondaparinux, direct factor Xa inhibitors or mechanical
interventions. Overall, the risk of bias was low in most of the studies. LMWH,
when compared with inactive control, significantly reduced the incidence of
symptomatic VTE (risk ratio (RR) 0.62, 95% confidence interval (CI) 0.41 to 0.93)
with no evidence of heterogeneity (I(2) = 0%). The number needed to treat to
prevent a symptomatic VTE was 60. LMWH was associated with a 60% increase in
major bleeding when compared with inactive control, although this was not
statistically significant (RR 1.57, 95% CI 0.69 to 3.60; I(2) = 10%). There was a
45% reduction in overall VTE (RR 0.55, 95% CI 0.34 to 0.88; I(2) = 0%) while for
symptomatic pulmonary embolism, asymptomatic VTE, minor bleeding and one-year
mortality the differences between the LMWH and control groups were not
statistically significant. The effect of the vitamin K antagonist warfarin on
preventing symptomatic VTE, measured in only one study, was not statistically
significant (RR 0.15, 95% CI 0.02 to 1.20). In one RCT of patients with myeloma,
LMWH was associated with a 67% reduction in symptomatic VTE (RR 0.33, 95% CI 0.14
to 0.83) compared with warfarin, with no differences in major bleeding.
Antithrombin, evaluated in one study on paediatric patients, had no significant
effect on VTE nor major bleeding when compared with inactive control.
AUTHORS' CONCLUSIONS: Primary thromboprophylaxis with LMWH significantly reduced
the incidence of symptomatic VTE in ambulatory cancer patients treated with
chemotherapy. However, the lack of power hampers definite conclusions on the
effects on major safety outcomes, which mandates additional studies to determine
the risk to benefit ratio of LMWH in this setting