Zafirlukast

Purpose: To evaluate the effects of zafirlukast on emergency department (ED) discharges and relapses following discharge in patients presenting with acute asthma.

Methods: In this 20-center, placebo-controlled, double-blind, randomized trial, patients with acute asthma received standardized treatment with prednisone and albuterol. 30 minutes after ED entry, patients were randomized to treatment with a single dose of zafirlukast 20 mg (Z20) or 160 mg (Z160), or placebo po. Patients who could be discharged at 240 minutes were eligible to continue in the trial and received prednisone 40 mg daily for 7 days, a [[Beta].sub.2]-agonist prn, and any other medications taken before ED entry. Both zafirlukast-treated groups continued on Z20 bid and placebo-treated patients continued on placebo bid for 28 days after ED discharge. Clinic visits were at days 10 and 28, and phone follow-ups were at days 3, 15, and 21 after ED discharge. Relapse was defined as an unscheduled ED visit/clinician contact for worsening asthma or a significant worsening of [FEV.sub.1] or diary indices at a clinic visit according to predefined criteria. Treatment failures were defined as an inability to be discharged from the ED or a relapse during the next 28 days. Analyses included all randomized patients and relapses occurring up to the day 28 clinic visit or within 3 days after the last dose of zafirlukast or placebo, whichever occurs first.

Results: 641 patients were randomized to treatment in the ED (Z20=158, Z160=162, placebo=321). Mean age was 32.5 years, and [FEV.sub.1] at ED entry was 38% of predicted. There was a trend for decreased admissions for Z160 patients compared with placebo (10% vs 15%, odds ratio 0.551, p=0.064). 545 patients continued after the ED visit (Z20=275, placebo=270). Zafirlukast reduced relapses compared with placebo (22% vs 29%; hazard ratio 0.674, p=0.023). Treatment failures also were significantly reduced compared with placebo (32% vs 39%; hazard ratio 0.701, p=0.009).

Conclusion: Zafirlukast reduces relapses and treatment failures in patients presenting to the ED with acute asthma.

Clinical Implications: Zafirlukast should be added to standard ED and discharge treatment regimens to improve asthma control and reduce healthcare utilization for patients with acute asthma.

Supported by: A research grant from Zeneca Pharmaceuticals.

Robert A Silverman, MD(*); C J Miller, MStat; Y Chen, PhD; C M Bonuccelli, MD; S G Simonson, MD and Zafirlukast Study Group. Long Island Jewish Medical Center, New Hyde Park, NY and Zeneca Pharmaceuticals, Wilmington, DE.

COPYRIGHT 1999 American College of Chest Physicians
COPYRIGHT 2000 Gale Group