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Effectiveness of the Leukotriene Receptor Antagonist Zafirlukast for Mild-to-Moderate Asthma: A Randomized, Double-Blind, Placebo-Controlled Trial

Samy Suissa, PhD; Rodolfo Dennis, MD, MSc; Pierre Ernst, MD, MSc; Odile Sheehy, MSc; and Sharon Wood-Dauphinee, PhD
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From the Royal Victoria Hospital, Montreal General Hospital, and McGill University, Montreal, Quebec, Canada; and the Universidad Javeriana, Bogota, Colombia. Acknowledgments: The authors thank Dr. Vincent Ciuryla and Mr. Kaylor Kowash of Zeneca Pharmaceuticals (Wilmington, Delaware) for their participation in the study design; Dr. Santiago Echeverri of Universidad Javeriana (Bogota, Colombia) for his assistance in data analysis; and Drs. Jean-Francois Boivin, Steven Grover, and Pierre Tousignant of McGill University (Montreal, Quebec, Canada) for their advice. Grant Support: In part by a grant from Zeneca Pharmaceuticals, Canada, Ltd., and by a doctoral fellowship from Boehringer-Ingelheim Pharmaceuticals, Canada (Dr. Dennis). Dr. Suissa is a research scholar of the Fonds de la Recherche en Sante du Quebec, and the McGill Pharmacoepidemiology Research Unit is funded by the Fonds de la Recherche en Sante du Quebec. Requests for Reprints: Samy Suissa, PhD, Division of Clinical Epidemiology, Royal Victoria Hospital, 687 Pine Avenue West, Ross 4.29, Montreal, Quebec H3A 1A1, Canada. Current Author Addresses: Dr. Suissa and Ms. Sheehy: Division of Clinical Epidemiology, Royal Victoria Hospital, 687 Pine Avenue West, Ross 4.29, Montreal, Quebec H3A 1A1, Canada.

Copyright ©2004 by the American College of Physicians

Ann Intern Med. 1997;126(3):177-183. doi:10.7326/0003-4819-126-3-199702010-00001
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Background: The increasing costs of managing asthma are due in part to the introduction of new medications, such as leukotriene receptor antagonists. These antagonists interfere with the action of leukotrienes, which are implicated in bronchoconstriction and the formation of airway edema in patients with asthma. Leukotriene receptor antagonists must be shown to be clinically and economically effective for their clinical use to be justified.

Objective: To assess the clinical and economic effectiveness of zafirlukast, a leukotriene receptor antagonist, in patients with mild-to-moderate asthma who might benefit from regular anti-inflammatory therapy.

Design: Randomized, double-blind, multicenter, placebo-controlled trial.

Setting: 28 outpatient clinics.

Patients: 146 patients with mild-to-moderate asthma who were 12 years of age or older, had not smoked cigarettes in the previous 6 months, had a smoking history of less than 10 pack-years, had an FEV1 at least 55% of the predicted value with no upper limit, had demonstrated bronchial hyperresponsiveness, and were symptomatic during the 7-day run-in period. All patients were seen every 2 to 3 weeks for 13 weeks.

Intervention: 103 patients received zafirlukast (20 mg twice daily), and 43 patients received placebo (twice daily). All patients received inhaled β-agonists as needed.

Measurements: Data were obtained from medical examinations, patient questionnaires, and daily diaries. The clinical effectiveness outcomes were days per month without asthma symptoms, limitation of activity, use of β-agonists, sleep disturbance, and episodes of asthma (the latter was a composite measure made up of the first four outcomes plus the occurrence of adverse events). The economic effectiveness outcomes were frequency and type of unscheduled health care contacts, use of β-agonist inhalers, consumption of nonasthma medications, and days of absence from work or school.

Results: The zafirlukast group had 89% more days without symptoms (adjusted rates, 7.0 compared with 3.7 days per month; P = 0.03), 89% more days without use of β-agonists (adjusted rates, 11.3 compared with 6.0 days per month; P = 0.001), and 98% more days without episodes of asthma (adjusted rates, 10.1 compared with 5.1 days per month; P = 0.003). They also had 55% (95% CI, 19% to 74%) fewer health care contacts (18.5 compared with 40.7 per 100 per month; P = 0.007) and 55% (CI, 3% to 79%) fewer days of absence from work or school (15.6 compared with 35.0 per 100 per month; P = 0.04). They used 17% fewer canisters of inhaled β-agonists (P = 0.17) and 19% less nonasthma medication (P > 0.2).

Conclusions: A daily regimen of zafirlukast added to as-needed inhaled β-agonists is more effective than β-agonists alone in treating mild-to-moderate asthma. The clinical and economic effectiveness of zafirlukast, a potential alternative to inhaled corticosteroids, provides further impetus to use regular “preventive” therapy in patients with mild-to-moderate asthma.


Grahic Jump Location
Figure 1.
Days without symptoms per month during the 13-week follow-up period, by treatment group.

No placebo recipients lacked symptoms on days 15 to 20 and day 25+.

Grahic Jump Location




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