Anticoagulation for the initial treatment of venous thromboembolism in patients with cancer

  • Review
  • Intervention

Authors


Abstract

Background

Compared to patients without cancer, patients with cancer receiving anticoagulant treatment for venous thromboembolism are more likely to develop recurrent venous thromboembolism (VTE).

Objectives

To compare the efficacy and safety of three types of anticoagulants (i.e. low molecular weight heparin (LMWH), unfractionated heparin (UFH), and fondaparinux) for the initial treatment of VTE in patients with cancer.

Search strategy

A comprehensive search for studies of anticoagulation in cancer patients including a January 2007 electronic search of : Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and ISI the Web of Science.

Selection criteria

Randomized clinical trials (RCTs) comparing LMWH, UFH, and fondaparinux in patients with cancer and objectively confirmed VTE.

Data collection and analysis

Using a standardized data form data was extracted in duplicate on methodological quality, participants, interventions and outcomes of interest that included all cause mortality, recurrent VTE, major bleeding, minor bleeding, thrombocytopenia and postphlebitic syndrome.

Main results

Of 3986 identified citations, 26 RCTs including cancer patients as subgroups fulfilled the inclusion criteria. Cancer subgroup data was obtained for 15 of the 26 RCTs. Thirteen studies compared a LMWH to UFH while one study compared fondaparinux to UFH and one study compared dalteparin to tinzaparin. Meta-analysis of 11 studies showed a statistically significant mortality reduction in patients treated with LMWH compared with those treated with UFH (Relative risk (RR) = 0.71; 95% confidence interval (CI) 0.52 to 0.98). There was little change in the results after excluding studies of lower methodological quality (RR = 0.72; 95% CI 0.52 to 1.00). A meta-analysis of three studies comparing LMWH with UFH in reducing recurrent VTE was inconclusive (RR = 0.78; 95% CI 0.29 to 2.08). No data was available for bleeding outcomes, thrombocytopenia or postphlebitic syndrome. Compared to UFH, fondaparinux showed a non-statistically significant benefit for the outcome of death (RR = 0.52; 95% CI 0.26 to 1.05). The one study comparing dalteparin to tinzaparin showed a non-statistically significant mortality reduction with dalteparin (RR = 0.86; 95% CI 0.43 to 1.73).

Authors' conclusions

Based on the included trials, LMWH is likely to be superior to UFH in the initial treatment of VTE in patients with cancer. However, there is a need for more trials to better address this research question in cancer patients. Moreover, researchers should consider making the raw data of RCTs available for individual patient data meta-analyses.

Plain language summary

Blood thinners for the initial treatment of blood clots in patients with cancer

Patients with cancer are at an increased risk of blood clots. The initial blood thinner (for the first few days) can consist of unfractionated heparin (infused intravenously) or low-molecular weight heparin (injected subcutaneously once or twice per day). These two blood thinners may have different efficacy and safety profiles. In this systematic review, data from 13 studies suggest that low molecular weight heparin is superior to unfractionated heparin in reducing mortality. However, there is not enough evidence to prove superiority in reducing recurrence of blood clots. The authors did not find data to compare the safety profile of these two medications.