Nationwide cohort study of the leukotriene receptor antagonist montelukast and incident or recurrent cardiovascular disease

J Allergy Clin Immunol. 2012 Mar;129(3):702-707.e2. doi: 10.1016/j.jaci.2011.11.052. Epub 2012 Jan 12.

Abstract

Background: The leukotriene pathway has been associated with an increased cardiovascular risk. However, the effects of the antileukotriene treatment used in asthmatic patients on cardiovascular outcomes have remained largely unexplored.

Objective: We sought to examine a potential protective role of the leukotriene receptor antagonist montelukast on future risk of incident and recurrent myocardial infarction and ischemic stroke.

Methods: A nationwide population-based cohort of approximately 7 million persons integrating data from the Prescribed Drug, Patient, Cause of Death, Income, Educational, and Emigration Registers was followed from July 1, 2005, to December 31, 2008. Analyses were performed in the whole population after exclusion of subjects with a prior cardiovascular diagnosis (incident events; sample size, n = 6,910,923 for myocardial infarction and n = 6,932,578 for stroke) and in subjects with a prior diagnosis (recurrent events; n = 153,937 and n = 132,291 for stroke and myocardial infarction, respectively).

Results: Cox proportional hazard ratios (HRs) did not reveal an association of montelukast use with incident events. In contrast to these findings, montelukast use was associated with a lower risk for recurrent stroke (HR, 0.62; 95% CI, 0.38-0.99) accounting for age, sex, education level, and yearly income. Adjusting the latter finding also for respiratory and cardiovascular medications and diagnoses revealed similar point estimates (HR, 0.62; 95% CI, 0.39-1.0). Post hoc analyses revealed a significant association of montelukast use with a lower risk for recurrent myocardial infarction in male subjects (HR, 0.65; 95% CI, 0.43-0.99).

Conclusion: These data provide a first indication for a potential role of the antiasthma drug montelukast for secondary prevention of cardiovascular disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetates / administration & dosage*
  • Acetates / adverse effects
  • Aged
  • Asthma / drug therapy*
  • Asthma / epidemiology*
  • Asthma / mortality
  • Asthma / physiopathology
  • Cardiovascular Diseases / drug therapy*
  • Cardiovascular Diseases / epidemiology*
  • Cardiovascular Diseases / mortality
  • Cardiovascular Diseases / physiopathology
  • Cohort Studies
  • Comorbidity
  • Cyclopropanes
  • Drug Utilization
  • Female
  • Follow-Up Studies
  • Humans
  • Leukotriene Antagonists / administration & dosage*
  • Leukotriene Antagonists / adverse effects
  • Male
  • Middle Aged
  • Quinolines / administration & dosage*
  • Quinolines / adverse effects
  • Risk
  • Sex Factors
  • Socioeconomic Factors
  • Sulfides
  • Survival Analysis
  • Sweden

Substances

  • Acetates
  • Cyclopropanes
  • Leukotriene Antagonists
  • Quinolines
  • Sulfides
  • montelukast