Meta-analysis on anticoagulation and prevention of thrombosis and mortality among patients with lung cancer

Thromb Res. 2017 Jun:154:28-34. doi: 10.1016/j.thromres.2017.03.024. Epub 2017 Apr 1.

Abstract

Background: Venous thromboembolism (Wickham et al., 2012 [1]) is a leading cause of morbidity and mortality among patients with cancer; however, primary thromboprophylaxis is not routinely recommended. We performed a systematic review and meta-analysis of randomized control trials (RCTs) to measure the impact of primary VTE prevention and its effect on mortality among patients with lung cancer.

Methods: With assistance from a master librarian, we searched Ovid, Scopus, DARE, CINAHL, MEDLINE, EMBASE, EBM reviews-Cochrane database of systematic reviews, EBM reviews-ACP journal, and EBM Reviews-Databases for relevant studies following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We included articles addressing the role of anticoagulation in patients with lung cancer for primary VTE prevention for outpatients. The clinical outcomes were VTE occurrence, all-cause mortality, major and clinically relevant non-major bleeding. The results are presented as odds ratio (OR) and data were analyzed using R and R META package (Version 0.8-2, Author: Guido Schwarzer).

Results: Eleven studies with 5107 patients were included for the final analysis. We found 50% lower VTE occurrence in the prophylaxis group with low molecular weight heparin (LMWH) (OR: 0.50; 95% Confidence Interval (CI): 0.38-0.66; I2: 0%) without an increased bleeding risk (OR: 2.03; 95% CI: 0.78-5.25; I2: 71.1%). We found a mortality benefit when we grouped all VTE prevention modalities [LMWH, Warfarin, unfractionated heparin (UFH)] (OR: 0.75; 95% CI: 0.58-0.96; I2: 18.4%), but no significant difference when LMWH (OR: 0.74; 95% CI: 0.49-1.11; I2: 56.9%) and warfarin were analyzed individually (OR: 0.75; 95% CI: 0.47-1.21; I2: 0%). We found higher odds of bleeding combining all treatment modalities (OR: 3.06; 95% CI: 1.64-5.72; I2: 64.4%) with the greatest occurrence in the warfarin group (OR: 5.42; 95% CI: 3.48-8.45; I2: 45.7%).

Conclusion: Primary VTE prophylaxis with LMWH reduces the occurrence of VTE among ambulatory patients with lung cancer, without apparent increase in bleeding risk. There is a measurable mortality benefit of anticoagulation strategies that remains elusive when the analysis is restricted to a single agent.

Keywords: Anticoagulation; Lung cancer; Prevention; Systematic review; Thromboembolism.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Anticoagulants / adverse effects
  • Anticoagulants / therapeutic use*
  • Hemorrhage / chemically induced
  • Heparin / adverse effects
  • Heparin / therapeutic use*
  • Heparin, Low-Molecular-Weight / adverse effects
  • Heparin, Low-Molecular-Weight / therapeutic use
  • Humans
  • Lung Neoplasms / complications*
  • Lung Neoplasms / mortality
  • Odds Ratio
  • Treatment Outcome
  • Venous Thromboembolism / etiology*
  • Venous Thromboembolism / mortality
  • Venous Thromboembolism / prevention & control*
  • Warfarin / adverse effects
  • Warfarin / therapeutic use*

Substances

  • Anticoagulants
  • Heparin, Low-Molecular-Weight
  • Warfarin
  • Heparin