Zafirlukast

Kathleen Rickard, MD*; Lisa Edwards, PhD and Christopher Kalberg, PhD.

PURPOSE: Rescue albuterol use is a useful measure of asthma control and disease severity. In this study, we compared the effects of fluticasone propionate (FP) with zafirlukast (ZAF) on exacerbation rates and clinical outcomes in patients with persistent asthma who were using low to high amounts of rescue albuterol prior to study start.

METHODS: A retrospective analysis of 1420 patients was performed on combined data from 4 randomized, double-blind clinical trials (4-12 weeks in duration), FP (88mcg BID) treatment was compared to ZAF (20mg BID) and placebo in the following sub-groups of patients: low (average of 0-4 puffs/day), medium (5-8 puffs/day), and high (9-12 puffs/day) use of rescue albuterol over the 7 days prior to randomization. Evaluations of exacerbation rates, morning [FEV.sub.1], AM PEF, rescue albuterol use, and symptom-free days were performed.

RESULTS: At baseline, the percent predicted [FEV.sub.1] in the subgroups decreased slightly with increasing albuterol use (range 69-63% predicted) and the mean age ranged from 29 to 35 years. Lower exacerbation rates were observed with FP and the rates with FP were similar across subgroups. Exacerbation rates in the ZAF and Placebo groups increased in line with baseline albuterol use. Exacerbation rates (expressed as % of patients) are shown in the following table:

(*) p=0.019 vs Placebo, (**)p [is less than or equal to] 0.044 vs. ZAF and Placebo

FP treatment resulted in significantly greater improvements in pulmonary function ([FEV.sub.1] and AM PEF) and rescue albuterol use in the low, medium, and high users as compared to ZAF (p [is less than or equal to] 0.028). FP significantly improved the percentage of symptom-free days in low and medium users as compared to ZAF (p [is less than or equal to] 0.002).

CONCLUSION: Patients using low, medium, and high amounts of rescue albuterol at baseline demonstrated greater improvements in pulmonary function and symptom control with FP treatment as compared with ZAF. Greater reductions in exacerbations rates were observed with FP treatment.

CLINICAL IMPLICATIONS: Low to high users of rescue albuterol receive greater benefit from a low dose of FP as compared to ZAF for the treatment of persistent asthma.

GRANT SUPPORT: Glaxo Wellcome

COPYRIGHT 2000 American College of Chest Physicians
COPYRIGHT 2001 Gale Group