Zafirlukast

Silverman RA, Nowak RM, Korenblat PE, et al. Zafirlukast treatment for acute asthma. Chest 2004; 126:1480-1489.

* Clinical Question

Does high-dose zafirlukast reduce the need for hospital admission in patients with an acute asthma exacerbation, and does 1 month of zafirlukast prevent relapse?

* Bottom Line

A high dose of zafirlukast (Accolate) slightly reduces the number of patients who have an extended stay in the emergency department (number needed to treat [NNT]=20). Continuing zafirlukast at a dose of 20 mg twice a day slightly improves outpatient outcomes, as well (NNT=20 to prevent relapse). Other studies have shown that inhaled corticosteroids are better long-term monotherapy for patients with asthma than leukotriene inhibitors. It is difficult to say whether this approach should be widely adopted--although the results are intriguing, I'd like to see at least one confirmatory study. This approach is, however, simple and relatively inexpensive. (LOE=lb)

Study Design Randomized controlled trial (double-blinded)

Allocation Concealed

Setting Emergency department (ED)

Synopsis

Zafirlukast is a leukotriene inhibitor, and the authors of this study speculate that its anti-inflammatory effect may improve outcomes in adolescents and adults with an acute exacerbation of asthma. Patients aged 12 to 65 years presenting with acute asthma were considered for inclusion if they had an forced expiratory volume at 1 second

(FEV[I.sub.1]) of less than 70% of predicted at admission to the ED and 25 minutes after a single dose of inhaled albuterol. They were excluded if they smoked; were pregnant; had recently used steroids or leukotriene inhibitors; needed intubation; or had pneumonia, fever, or any serious comorbidity.

Patients (n=641) were randomized (allocation apparently concealed) to zafirlukast 160 mg in a single dose, zafirlukast 20 mg in a single dose, or placebo in a 1:1:2 ratio. All patients received 60 mg oral prednisone and additional doses of nebulized albuterol at 60, 120, and 180 minutes. After 3.5 hours in the ED, patients were re-evaluated, and it was determined whether they were ready for discharge or required additional care. Although physicians were encouraged to use standard criteria for this decision, the final decision was theirs alone.

Patients discharged from the ED after 4 hours entered a second phase of the study. Those who received any dose of zafirlukast continued to receive 20 mg twice per day (n=276), while patients who received placebo in the ED received matching placebo twice per day (n=270). All patients received 7 days of prednisone 20 mg twice a day, were given an albuterol inhaler, and told to resume any previous asthma medications other than leukotriene inhibitors.

The primary outcomes were the likelihood of relapse in the outpatient setting, defined as any unscheduled visit to the outpatient clinic or ED during the subsequent month, and the rate of requiring care beyond 4 hours in the ED for the initial visit (extended care). Patients kept a symptom diary during the month of outpatient followup, which was completed by 86% in the zafirlukast group and 81% in the placebo group. Groups were balanced at the start of the study, and analysis was by intention to treat.

Patients receiving 160 mg of zafirlukast (drug cost, approximately $10) were slightly less likely to require extended care in the ED than those receiving 20 mg or placebo (9.9%, 16.5%, and 15.0%, respectively; P=.05; number needed to treat [NNT]=20). Because we are not told how many patients actually required hospitalization, I suspect that there was no difference. During the outpatient follow-up period, patients who continued to receive zafirlukast were slightly less likely to relapse (23.6% vs 28.9%; P=.05; NNT=20). Regarding secondary outcomes, patients receiving the high-dose zafirlukast had a lower dyspnea score after 3.5 hours in the ED than those receiving either low-dose zafirlukast or placebo, and those taking zafirlukast during the outpatient follow-up period had small advantages over those taking placebo in the symptom diary scores, although these were of questionable clinical significance.

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