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The Effect of Montelukast and Low-Dose Theophylline on Cardiovascular Disease Risk Factors in Asthmatics^*

^* From the Department of Preventive Medicine (Drs. Allayee and Conti, Ms. Hartiala, and Mr. Lee), Keck School of Medicine, University of Southern California, Los Angeles, CA; Department of Medicine, (Dr. Mehrabian), David Geffen School of Medicine at UCLA, Los Angeles, CA; Department of Medicine, (Dr. Irvin), College of Medicine, University of Vermont, Burlington, VT; and Centers for Clinical Pediatric Pharmacology and Pharmacogenetics, Nemours Children’s Clinic (Dr. Lima), Jacksonville, FL.

Correspondence to: Hooman Allayee, PhD, Institute for Genetic Medicine, USC Keck School of Medicine, 2250 Alcazar St, IGM 206, Los Angeles, CA 90033; e-mail: hallayee{at}usc.edu

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Key Words: cardiovascular disease • 5-lipoxygenase • inflammation • leukotriene inhibitors • lipids