Anticoagulant therapy for acute venous thrombo-embolism in cancer patients: A systematic review and network meta-analysis

PLoS One. 2019 Mar 21;14(3):e0213940. doi: 10.1371/journal.pone.0213940. eCollection 2019.

Abstract

Background: Low-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.

Methods: We 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.

Results: We 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.

Conclusions: DOAC 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.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Acute Disease
  • Administration, Oral
  • Anticoagulants / administration & dosage
  • Anticoagulants / adverse effects
  • Anticoagulants / therapeutic use*
  • Factor Xa Inhibitors / administration & dosage
  • Factor Xa Inhibitors / adverse effects
  • Factor Xa Inhibitors / therapeutic use
  • Female
  • Hemorrhage / etiology
  • Heparin, Low-Molecular-Weight / administration & dosage
  • Heparin, Low-Molecular-Weight / adverse effects
  • Heparin, Low-Molecular-Weight / therapeutic use
  • Humans
  • Male
  • Neoplasms / complications*
  • Network Meta-Analysis
  • Recurrence
  • Risk Factors
  • Safety
  • Secondary Prevention
  • Venous Thromboembolism / drug therapy*
  • Venous Thromboembolism / etiology*
  • Venous Thromboembolism / prevention & control
  • Vitamin K / antagonists & inhibitors

Substances

  • Anticoagulants
  • Factor Xa Inhibitors
  • Heparin, Low-Molecular-Weight
  • Vitamin K

Grants and funding

The author(s) received no specific funding for this work.