montelukast and Cardiovascular-Diseases

Leukotrienes are important lipid mediators of inflammation arising from arachidonic acid cascade. They are implicated in vascular inflammation and produced in different pathologic conditions as atherosclerosis, stroke and myocardial infarction. Different studies have investigated the role of leukotriene receptor antagonist (LTRA) in reducing some cardiovascular events, especially in animals. We conducted a systematic review of both in vivo animal and human studies to determine the potential role of leukotriene receptor antagonist in reducing cardiovascular and cerebrovascular events.. Data sources: Pubmed, Embase and Cochrane database.. Two reviewers independently screened potentially eligible articles and extracted relevant data.. A total of 28 studies were included, of which 26 were conducted in animals, and 2 in humans.. All animal studies reported that using a leukotriene receptor antagonist brings to a reduction of either myocardial infarction, ischemic stroke, or atherosclerosis risk. Similar results were obtained from two clinical trials on humans, suggesting a potential role of montelukast in reducing some cardiovascular diseases.

Topics: Acetates; Animals; Cardiovascular Diseases; Cardiovascular System; Cerebrovascular Disorders; Clinical Trials as Topic; Cyclopropanes; Humans; Leukotriene Antagonists; Quinolines; Risk Factors; Sulfides

Cysteinyl leukotrienes (LTC4, LTD4, and LTE4) are pro-inflammatory mediators of the 5-lipooxygenase (5-LO) pathway, that play an important role in bronchoconstriction, but can also enhance endothelial cell permeability and myocardial contractility, and are involved in many other inflammatory conditions. In the late 1990s, leukotriene receptor antagonists (LTRAs) were introduced in therapy for asthma and later on, approved for the relief of the symptoms of allergic rhinitis, chronic obstructive pulmonary disease, and urticaria. In addition, it has been shown that LTRAs may have a potential role in preventing atherosclerosis progression.. The aims of this short review are to delineate the potential cardiovascular protective role of a LTRA, montelukast, beyond its traditional use, and to foster the design of appropriate clinical trials to test this hypothesis.. What it is known about leukotriene receptor antagonists? •Leukotriene receptor antagonist, such as montelukast and zafirlukast, is used in asthma, COPD, and allergic rhinitis. • Montelukast is the most prescribed CysLT

Topics: Acetates; Animals; Arachidonate 5-Lipoxygenase; Arachidonic Acid; Cardiovascular Diseases; Cyclopropanes; Humans; Leukotriene Antagonists; Quinolines; Signal Transduction; Sulfides

Recent studies have implicated the 5-lipoxygenase/leukotriene (LT) pathway in cardiovascular disease (CVD), which may have important implications for asthmatics because several drugs that target this pathway are currently used to treat asthma. We sought to determine whether montelukast, a cysteinyl LT antagonist, and low-dose theophylline affected serum inflammatory and lipid CVD risk factors in a recently completed clinical trial in asthmatic patients.. Patients were randomized to receive either montelukast (10 mg/d), theophylline (300 mg/d), or placebo. A baseline run-in period of 7 to 14 days was followed by treatment for 6 months. Serum levels of C-reactive protein (CRP), interleukin-6, total cholesterol, triglycerides, low-density lipoprotein cholesterol, and high-density cholesterol (HDL-C) were measured 1 month and 6 months after treatment.. Patients with moderate-to-severe asthma receiving montelukast (n = 60) had significantly lower serum CRP compared to placebo (n = 73) after 1 month (1.7 mg/L vs 3.2 mg/L, respectively; p < 0.006) and 6 months of treatment (2.3 mg/L vs 3.5 mg/L, respectively; p < 0.04). At both time points, serum levels of all lipids were also significantly lower in the montelukast and theophylline groups compared to placebo, but these effects were primarily observed in individuals who were also receiving inhaled corticosteroids as monotherapy for asthma.. Asthmatic patients receiving montelukast and, to some extent, low-dose theophylline have lower levels of CVD-associated inflammatory biomarkers and lipid levels. These observations suggest these asthma medications may have some beneficial value in asthmatics with respect to CVD risk, although the effects on HDL-C levels should also be taken into consideration.

Topics: Acetates; Adult; Anti-Asthmatic Agents; Asthma; Biomarkers; C-Reactive Protein; Cardiovascular Diseases; Cyclopropanes; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Interleukin-6; Lipids; Male; Middle Aged; Quinolines; Risk Factors; Sulfides; Theophylline

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

Topics: Acetates; Aged; Asthma; Cardiovascular Diseases; Cohort Studies; Comorbidity; Cyclopropanes; Drug Utilization; Female; Follow-Up Studies; Humans; Leukotriene Antagonists; Male; Middle Aged; Quinolines; Risk; Sex Factors; Socioeconomic Factors; Sulfides; Survival Analysis; Sweden