Direct Oral Anticoagulants Versus Low-Molecular-Weight Heparin in Patients With Cancer-Associated Thrombosis: A Meta-Analysis of Randomized Controlled Trials

Am J Cardiol. 2025 Nov 1:254:32-41. doi: 10.1016/j.amjcard.2025.06.022. Epub 2025 Jun 25.

Abstract

Cancer-associated thrombosis (CAT) is a significant cause of morbidity and mortality in patients with cancer. Determining the optimal anticoagulant remains a clinical challenge. This meta-analysis aimed to compare the efficacy and safety of direct oral anticoagulants (DOACs) and low-molecular-weight heparin (LMWH) for CAT treatment. We systematically searched databases for randomized controlled trials (RCTs) comparing DOACs and LMWH in patients diagnosed with CAT. Efficacy outcomes were recurrent venous thromboembolism (VTE), deep vein thrombosis (DVT), and pulmonary embolism (PE). Safety outcomes comprised total bleeding, major bleeding, clinically relevant nonmajor bleeding (CRNMB), and all-cause mortality. We calculated incidence risk ratios (IRRs) with 95% confidence intervals (CIs) using a random-effects model. Subgroup analyses were conducted based on administered DOAC type. We identified 10 RCTs with 4713 participants (mean age 64.63 years, 50.58% male), including 2390 receiving DOACs and 2323 receiving LMWH. Compared to LMWH, the DOACs group demonstrated a statistically significant reduction in the incidence of VTE (IRR = 0.66, 95% CI 0.56 to 0.79). Total bleeding (IRR = 1.10, 95% CI 0.80;1.50) and mortality (IRR = 1.00, 95% CI, 0.89-1.12) did not differ significantly. Sensitivity analyses of studies with >100 participants and 6-month follow-up were consistent with overall results. In conclusion, DOACs were more effective than LMWH in reducing the risk of recurrent VTE and DVT in patients with CAT, with comparable safety profiles. The improved efficacy of DOACs positions them as a potentially advantageous therapeutic option for this patient population. Further research is warranted to optimize DOAC use in different cancer types and patient subgroups.

Keywords: cancer-associated thrombosis; direct oral anticoagulants; low-molecular-weight heparin; meta-analysis.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Administration, Oral
  • Anticoagulants* / administration & dosage
  • Anticoagulants* / therapeutic use
  • Heparin, Low-Molecular-Weight* / therapeutic use
  • Humans
  • Neoplasms* / complications
  • Pulmonary Embolism / etiology
  • Randomized Controlled Trials as Topic
  • Thrombosis* / drug therapy
  • Thrombosis* / etiology
  • Venous Thromboembolism / etiology
  • Venous Thromboembolism / prevention & control
  • Venous Thrombosis* / drug therapy
  • Venous Thrombosis* / etiology

Substances

  • Anticoagulants
  • Heparin, Low-Molecular-Weight