Leukotriene receptor antagonism with montelukast as a possible therapeutic for venous thromboembolism prophylaxis: An observational study

Prostaglandins Other Lipid Mediat. 2022 Aug:161:106649. doi: 10.1016/j.prostaglandins.2022.106649. Epub 2022 May 18.

Abstract

Background: Arachidonic acid (AA), which is metabolized via the cyclooxygenase (COX) and the lipoxygenase (LOX) pathways, was found to be associated with venous thromboembolism (VTE). Metabolites of the LOX pathway include cysteinyl (Cys) Leukotrienes (LT), potent proinflammatory mediators, which have also been implicated in cardiovascular disease.

Objective: The purpose of this study was to examine if cysteinyl leukotriene receptor blockade by montelukast, lowers the risk of VTE.

Methods: We conducted a retrospective cohort study examining VTE risk among COPD patients from the United States Department of Veterans Affairs. We use propensity score matching and Cox survival models to estimate the hazard ratio comparing montelukast exposure to non-exposure. Montelukast exposure was associated with a 15.9% reduction in risk of VTE compared to those unexposed (HR= 0.841; 95% CI= (0.758-0.934)).

Conclusion: The results of this study demonstrate that targeting LTs might be beneficial for VTE prophylaxis using the clinically available LT inhibitor, montelukast. Importantly, further research on LTs is warranted to fully understand and validate this relationship.

Keywords: Leukotrienes receptor antagonism; Montelukast; Venous thromboembolism.

Publication types

  • Observational Study
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetates / pharmacology
  • Acetates / therapeutic use
  • Cyclopropanes
  • Humans
  • Leukotriene Antagonists / pharmacology
  • Leukotriene Antagonists / therapeutic use
  • Leukotrienes
  • Quinolines* / pharmacology
  • Quinolines* / therapeutic use
  • Receptors, Leukotriene / metabolism
  • Retrospective Studies
  • Sulfides
  • Venous Thromboembolism* / drug therapy
  • Venous Thromboembolism* / prevention & control

Substances

  • Acetates
  • Cyclopropanes
  • Leukotriene Antagonists
  • Leukotrienes
  • Quinolines
  • Receptors, Leukotriene
  • Sulfides
  • montelukast