Asthma: fatal exacerbations with long-acting beta2 agonist therapy without concomitant steroid therapy.
(1) In France, two long-acting inhaled beta2 agonists (salmeterol and formoterol) are marketed for long term symptomatic treatment of asthma, in combination with antiinflammatory treatment with an inhaled steroid. (2) A double-blind placebo-controlled trial of salmeterol in about 26 000 patients was stopped prematurely in 2003 due to an excess of serious asthma attacks and asthma-related deaths in the salmeterol group. There were 13 asthma-related deaths after 28 weeks of salmeterol therapy, versus only three in the placebo group, for a relative risk of about 4 and a 95% confidence interval of 1.2 to 15.3. (3) This increased mortality was mainly observed in the subgroup of patients who were not using a steroid (53% of all patients). Nine of these patients died while taking salmeterol versus none on placebo. (4) Three smaller trials showed an increase in severe asthma attacks in patients using formoterol without a steroid. For example, in one trial nine of 271 patients on formoterol had severe asthma attacks, versus two of 277 patients on placebo. A meta-analysis of 19 placebo-controlled trials of long-acting beta2 agonists showed an increase in severe asthma attacks in both adults and children. Exacerbations have also been attributed to salmeterol, including in patients using a steroid. (5) In practice, for long-term treatment, long-acting beta2 agonists must never be used without concomitant inhaled steroid therapy.
D000280:Administration, Inhalation; D000318:Adrenergic beta-Agonists / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D000328:Adult; D000420:Albuterol / Q000008:administration & dosage / Q000009:adverse effects* / Q000031:analogs & derivatives / Q000627:therapeutic use; D001249:Asthma / Q000188:drug therapy* / Q000401:mortality; D002648:Child; D002986:Clinical Trials as Topic; D004359:Drug Therapy, Combination; D004983:Ethanolamines / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D005602:France; D006801:Humans; D015201:Meta-Analysis as Topic; D013256:Steroids / Q000627:therapeutic use*
D000318:Adrenergic beta-Agonists; D004983:Ethanolamines; D013256:Steroids; D000420:Albuterol