Abstract

BackgroundLow-molecular-weight heparin (LMWH) is usually recommended for the treatment of cancer-associated thrombosis (CAT) but this treatment requires burdensome daily injections. We did a systematic review to compare the efficacy and safety of direct oral anticoagulants (DOAC), vitamin K antagonists (VKA) and LMWH in patients with CAT.MethodsWe searched Pubmed, Embase and CENTRAL for randomised controlled trials comparing DOAC, VKA and LMWH in patients with CAT. Pairwise and network meta-analyses were computed for venous thromboembolism (VTE) recurrence and bleeding complications.ResultsWe identified 14 studies, including 4,661 patients. In pairwise comparison, DOAC were superior to LMWH to prevent VTE recurrence (HR 0.63; 95% CI 0.42–0.96) and LMWH was superior to VKA (HR 0.53; 95% CI 0.40–0.70). The rate of major bleeding was higher with DOAC compared to LMWH (HR 1.78; 95% CI 1.11–2.87). In the network meta-analysis, DOAC had a lower, but non-significant, rate of VTE recurrence compared to LMWH (HR 0.74; 95% CI 0.54–1.01). Both DOAC (HR 0.42; 95% CI 0.29–0.61) and LMWH (HR 0.57; 95% CI 0.44–0.75) were associated with lower rates of recurrence compared to VKA. No significant difference in major bleeding rate was observed in the network meta-analysis. Inconsistency was observed between pairwise and network meta-analysis comparisons for major bleeding.ConclusionsDOAC are effective to prevent VTE recurrence in patients with CAT but are associated with an increased risk of bleeding compared to LMWH. The choice of anticoagulant should be personalised, taking into account the patient’s bleeding risk, including cancer site, and patient’s values and preferences.

Highlights

  • The management of cancer-associated thrombosis (CAT) is challenging

  • direct oral anticoagulants (DOAC) were superior to Low-molecular-weight heparin (LMWH) to prevent venous thromboembolic event (VTE) recurrence (HR 0.63; 95% CI 0.42–0.96) and LMWH was superior to vitamin K antagonists (VKA) (HR 0.53; 95% CI 0.40–0.70)

  • The rate of major bleeding was higher with DOAC compared to LMWH (HR 1.78; 95% CI 1.11–2.87)

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Summary

Introduction

The management of cancer-associated thrombosis (CAT) is challenging. The risk of developing a first venous thromboembolic event (VTE) in cancer patients is seven–fold higher than in the general population [1]. The standard of care of VTE in patients with cancer consists of subcutaneous low molecular weight heparin (LMWH), for an initial duration of 6 months, which is extended with either LMWH or VKA for an indefinite duration, as long as the cancer is not considered in remission [3]. This recommendation is based on randomised studies showing a reduced risk of VTE recurrence in cancer patients receiving LMWH compared with antivitamin K therapy [5,6,7,8]. We did a systematic review to compare the efficacy and safety of direct oral anticoagulants (DOAC), vitamin K antagonists (VKA) and LMWH in patients with CAT

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