Non-vitamin K antagonist oral anticoagulants and the treatment of venous thromboembolism in cancer patients: a semi systematic review and meta-analysis of safety and efficacy outcomes

PLoS One. 2014 Dec 5;9(12):e114445. doi: 10.1371/journal.pone.0114445. eCollection 2014.

Abstract

Background: This study sought to investigate the relative efficacy and safety of non-vitamin K oral anticoagulants (NOACs) for the treatment of venous thromboembolism (VTE) in cancer patients.

Methods: A systematic search of the PubMed, EMBASE, and ClinicalTrials.gov databases identified all multicentre, randomised phase III trials investigating the initial use of NOAC against a vitamin K antagonist (VKA) together with subcutaneous heparin or low molecular weight heparin (upstart) for treatment of VTE. Outcomes of interest were recurrent VTE (deep venous thrombosis or pulmonary embolism), and clinically relevant bleeding.

Results: Four randomised controlled phase III trials were included, comprising a total of 19,060 patients randomised to either NOAC or VKA. For patients with active cancer (N = 759), the analysis on the efficacy outcomes demonstrated a trend in favour of NOAC (OR 0.56, 95% CI 0.28-1.13). Similar, analyses on the safety outcomes comparing NOAC to VKA and enoxaparin demonstrated a trend in favour of NOAC (OR 0.88, 95% CI 0.57-1.35).

Conclusion: Point estimates of the effect size suggest an important estimated beneficial effect of NOAC in the treatment of VTE in cancer, in terms of efficacy and safety, but given the small numbers of patients with cancer in the randomised trials, statistical significance was not achieved.

Publication types

  • Comparative Study
  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Administration, Oral
  • Anticoagulants / adverse effects
  • Anticoagulants / therapeutic use*
  • Clinical Trials, Phase III as Topic
  • Enoxaparin / adverse effects
  • Enoxaparin / therapeutic use*
  • Humans
  • Neoplasms / drug therapy*
  • Randomized Controlled Trials as Topic
  • Venous Thromboembolism / drug therapy*
  • Vitamin K

Substances

  • Anticoagulants
  • Enoxaparin
  • Vitamin K

Grants and funding

The Obel Family Foundation supported this study. The sponsor had no role in the study design; in the collection, analysis, and interpretation of the data; in the writing of this report; or in the decision to submit the paper for publication. The corresponding authors had full access to all the data in the study and had final responsibility for the decision to submit for publication.