Clinical Question: Is guideline-driven care of patients with asthma using stepwise increases in salmeterol-fluticasone therapy more effective than using fluticasone alone?

Setting: Outpatient (any)

Study Design: Randomized controlled trial (double-blinded)

Allocation: Uncertain

Synopsis: This year-long study involved 3,421 patients between 12 and 80 years of age who had at least a six-month history of asthma, had fewer than 10 pack-years of tobacco use, and had not used oral or long-acting beta agonists in the two weeks before enrollment. The study began with a four-week run-in period during which patients continued their usual treatment.

Patients without two well-controlled weeks were randomized (concealment of allocation not described) to receive salmeterol-fluticasone or fluticasone propionate alone. Each treatment group also was stratified according to the use of inhaled corticosteroids for the six months before enrollment. In this phase, dosages of medication were increased until asthma was totally controlled or until maximum dosages of medication were used (i.e., salmeterol-fluticasone, 50/500 mcg twice a day; fluticasone, 500 mcg twice a day). The patients then were maintained on the dosage needed to achieve total control (or the maximum dose) for the rest of the year.

Total asthma control was defined as seven of eight weeks with no daytime symptoms; no use of rescue medications; a morning peak expiratory flow of at least 80 percent of predicted; and no nighttime awakenings, no exacerbations, no emergency department visits, and no adverse events related to the medication. Well-controlled asthma was defined similarly, except as follows: no more than two days with a symptom score higher than 1, and the use of rescue medication on no more than two days and no more than four doses per week. These definitions came from the Global Initiative for Asthma and the National Institutes of Health. The primary study objective, assessed by intention to treat, was to determine the proportion of patients who achieved well-controlled asthma.

Significant improvement was noted in the group receiving salmeterol-fluticasone compared with the group receiving fluticasone alone throughout all phases of the study, regardless of their baseline steroid use. One concern of this study, however, was that the guidelines called for an automatic dosage escalation of products manufactured by the study sponsor to achieve total asthma control.

Bottom Line: Patients with asthma who are treated with stepwise increases in salmeterol-fluticasone are more likely to achieve total control or be well controlled by the end of 12 weeks and at the end of one year than patients using fluticasone alone. (Level of Evidence: 1b)