Level 2: Mid-level evidence

A recent systematic review evaluated 19 randomized placebo-controlled trials of long-acting beta-agonist (LABA) use for at least three months in 33,826 patients with asthma (Ann Intern Med. 2006;144:904-912). Mean trial duration was six months (range 3-12 months), and overall follow-up was 16,848 patient-years. Dropout rates were 20.3% with LABA and 22.6% with placebo.

In a meta-analysis of 12 trials with 5,091 patients, hospitalization for asthma exacerbation occurred in 1.72% of LABA patients compared with 0.6% of those on placebo (NNH 89). Life-threatening asthma exacerbation occurred in 0.32% of LABA patients compared with 0.17% of placebo recipients (NNH 666), based on meta-analysis of seven trials (N=29,981). Comparing LABA vs. placebo, there were 15 vs. 3 asthma-related deaths in 14 trials with reported asthma-related deaths (NNH 1,428); in a sensitivity analysis assuming no deaths in 28 additional trials, the absolute increase in risk was 0.6% (NNH 1,666).

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The FDA has updated product labels for all LABAs regarding the possible increased risk of severe asthma episodes and death (FDA MedWatch. 2005 Nov 18; full-text available online without charge at www.fda.gov/medwatch/safety/2005/safety05.htm#LABA. Accessed March 15, 2007). The Medication Guide with this information is given to patients when prescriptions are filled or refilled. An accompanying public health advisory (www.fda.gov/cder/drug/advisory/LABA.htm. Accessed March 15, 2007) recommends that LABAs should be used only if asthma control is inadequate with other medications, including low- to medium-dose corticosteroids. LABAs should not be used as first-line therapy for asthma or as treatment for worsening symptoms, and they do not relieve sudden wheezing (so short-acting bronchodilators should be available at all times). Additionally, asthma medicines (including LABAs) should not be stopped by patients unless cessation has been discussed with a health-care professional.