B-agonistas inhalatorios de larga duración ¿Aumentan mortalidad por asma?

Un meta-análisis publicado en la edición del 5 de junio de 2006 del Annals of Internal Medicine sugiere que beta agonistas inhalatorios como el salmeterol y formoterol aumentan el riesgo de exacerbación de asma, necesidad de intubación y muerte.
Los autores reconocen limitaciones de este estudio dado por el bajo número de muertes y el hecho que 28 de los estudios analizados no daban resultados en los "end-points" que búscaban.


Meta-Analysis: Effect of Long-Acting ß-Agonists on Severe Asthma Exacerbations and Asthma-Related Deaths.
Shelley R. Salpeter, MD; Nicholas S. Buckley; Thomas M. Ormiston, MD; and Edwin E. Salpeter, PhD
Ann Intern Med 2006; 144: 901-12
Background: Long-acting ß-agonists may increase the risk for fatal and nonfatal asthma exacerbations.
Purpose: To assess the risk for severe, life-threatening, or fatal asthma exacerbations associated with long-acting ß-agonists.
Data Sources: English- and non–English-language searches of MEDLINE, EMBASE, and Cochrane databases; the U.S. Food and Drug Administration Web site; and references of selected reviews through December 2005.
Study Selection: Randomized, placebo-controlled trials that lasted at least 3 months and evaluated long-acting ß-agonist use in patients with asthma. All trials allowed the use of as-needed short-acting ß-agonists.
Data Extraction: Outcomes measured were Peto odds ratio (OR) and risk difference of severe exacerbations requiring hospitalization, life-threatening exacerbations requiring intubation and ventilation, and asthma-related deaths. The OR for asthma-related deaths was obtained from the Salmeterol Multi-center Asthma Research Trial (SMART).
Data Synthesis: Pooled results from 19 trials with 33 826 participants found that long-acting ß-agonists increased exacerbations requiring hospitalization (OR, 2.6 [95% CI, 1.6 to 4.3]) and life-threatening exacerbations (OR, 1.8 [CI, 1.1 to 2.9]) compared with placebo. Hospitalizations were statistically significantly increased with salmeterol (OR, 1.7 [CI, 1.1 to 2.7]) and formoterol (OR, 3.2 [CI, 1.7 to 6.0]) and in children (OR, 3.9 [CI, 1.7 to 8.8]) and adults (OR, 2.0 [CI, 1.1 to 3.9]). The absolute increase in hospitalization was 0.7% (CI, 0.1% to 1.3%) over 6 months. The risk for asthma-related deaths was increased (OR, 3.5 [CI, 1.3 to 9.3]), with a pooled risk difference of 0.07% (CI, 0.01% to 0.1%).
Limitations: The small number of deaths limited the reliability in assessing this risk, and 28 studies did not report information on the outcomes of interest.
Conclusions: Long-acting ß-agonists have been shown to increase severe and life-threatening asthma exacerbations, as well as asthma-related deaths.