title: Meta-analysis on anticoagulation and prevention of thrombosis and mortality among patients with lung cancer.
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%).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Internal Medicine, John Stroger Jr. Hospital, Chicago, IL, United States.
authors.forename: H E
authors.initials: HE
authors.lastname: Fuentes
authors.affiliation: Department of Pathology, University of Illinois at Chicago, Chicago, IL, United States.
authors.forename: D M
authors.initials: DM
authors.lastname: Oramas
authors.affiliation: Department of Internal Medicine, John Stroger Jr. Hospital, Chicago, IL, United States.
authors.forename: L H
authors.initials: LH
authors.lastname: Paz
authors.affiliation: Department of Cardiology - Vascular Medicine, Mayo Clinic, Rochester, MN, United States.
authors.forename: A I
authors.initials: AI
authors.lastname: Casanegra
authors.affiliation: Division of Medical Oncology, Mayo Clinic, Rochester, MN, United States.
authors.forename: A S
authors.initials: AS
authors.lastname: Mansfield
authors.affiliation: Cardiology - Vascular Medicine, Northshore University Healthsystem, Evanston, IL, United States. Electronic address: atafur@northshore.org.
authors.forename: A J
authors.initials: AJ
authors.lastname: Tafur
mesh_terms: D000925:Anticoagulants / Q000009:adverse effects / Q000627:therapeutic use*; D006470:Hemorrhage / Q000139:chemically induced; D006493:Heparin / Q000009:adverse effects / Q000627:therapeutic use*; D006495:Heparin, Low-Molecular-Weight / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D008175:Lung Neoplasms / Q000150:complications* / Q000401:mortality; D016017:Odds Ratio; D016896:Treatment Outcome; D054556:Venous Thromboembolism / Q000209:etiology* / Q000401:mortality / Q000517:prevention & control*; D014859:Warfarin / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D000925:Anticoagulants; D006495:Heparin, Low-Molecular-Weight; D014859:Warfarin; D006493:Heparin
keywords: Anticoagulation; Lung cancer; Prevention; Systematic review; Thromboembolism