Zafirlukast

There are 2 million emergency department visits and almost 500,000 hospital admissions annually in the United States because of acute asthma. Most patients who are evaluated and treated in the emergency department improve enough to be discharged, but their asthma symptoms may persist for days or weeks. Relapse rates have been reported ranging from 10 percent within seven days of discharge to 31 percent within 10 to 21 days of discharge. Cysteinyl leukotrienes, shown to be mediators of inflammation and bronchoconstriction in patients with asthma, may be markedly elevated during acute asthma episodes. Leukotriene-modifying medications have been shown to be effective in the treatment of chronic asthma, but no studies have evaluated this class of medications in acute asthma episodes. Silverman and colleagues assessed the effectiveness of zafirlukast (Accolate), an oral leukotriene receptor antagonist, when added to standarized treatment of patients with acute asthma who visited emergency departments.

The authors conducted a randomized, double-blind, multicenter study of 641 patients treated for acute asthma at 20 different emergency departments. Patients were enrolled in the study if they had symptoms of acute asthma and had a forced expiratory volume in one second ([FEV.sub.1]) of less than 70 percent predicted at the time of admission and 25 minutes after a single aerosol treatment with 2.5 mg of albuterol. They were excluded from the study if they had a smoking history of more than 10 pack-years, a positive pregnancy test result, recent corticosteroid use, or recent use of a leukotriene-modifying drug. Patients received standard protocol for acute asthma treatment in the emergency department and were randomized to receive zafirlukast in a one-time 160-mg, 20-mg, or placebo in the emergency department. They were then discharged to receive zafirlukast in a dosage of 20 mg twice per day during the study period or placebo. Patients were contacted by telephone at days 3, 15, and 21 to assess asthma symptoms, medication compliance, whether the patients had sought additional asthma treatment, and adverse events. They also were followed in a clinic at 10 and 28 days after discharge from the emergency department, and patients recorded data on a home diary card. Main outcome measures were time to relapse after discharge from the emergency department, rate of extended care in the emergency department (i.e., more than four hours or hospitalization), change in [FEV.sub.1], and symptoms.

At the end of the study, patients who received zafirlukast were significantly less likely to have a relapse when compared with patients who received placebo. Patients treated with 160 mg of zafirlukast had a 34 percent relative risk reduction in the need for extended care. They also had a greater improvement in [FEV.sub.1] and dyspnea when compared with patients who received placebo. Those who continued to receive zafirlukast in a dosage of 20 mg twice per day had even greater improvement in their [FEV.sub.1] and symptom measures during the outpatient period. Adverse events were similar between the zafirlukast and placebo groups, with headache being the most common.

The authors conclude that zafirlukast in a dosage of 20 mg twice per day, when added to standard care of acute asthma, reduces the risk of relapse. Also, the use of 160 mg of zafirlukast in the emergency department reduces the rate of extended care. Zafirlukast is a useful treatment adjunct in patients who have acute asthma symptoms.

KARL E. MILLER, M.D.

Silverman RA, et al. Zafirlukast treatment for acute asthma. Evaluation in a randomized, double-blind, multicenter trial. Chest November 2004;126:1480-9.

COPYRIGHT 2005 American Academy of Family Physicians
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