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Regular treatment with salmeterol for chronic asthma: serious adverse eventsCates CJ, Cates MJ
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SummarySerious adverse events were increased in clinical trials comparing regular salmeterol to pIaceboIn view of concerns regarding the safety of regular long-acting beta2-agonist inhalers in asthma, this review has gathered all the information available regarding all-cause serious adverse events (both fatal and non-fatal) from clinical trials comparing regular salmeterol to placebo or salbutamol. Compared with placebo, mortality increased with regular salmeterol, but this was not statistically significant. Non-fatal serious adverse events increased with salmeterol in comparison with placebo; for every 188 people treated with salmeterol for 28 weeks, one extra non-fatal event occurred in comparison with placebo. No significant differences were found comparing regular salmeterol with regular salbutamol. In patients who were not taking inhaled corticosteroids the two large surveillance studies showed similar sized increases in the risk of asthma-related death. For patients whose asthma is not well-controlled on moderate doses of inhaled corticosteroids, additional salmeterol can give symptomatic benefit but this may be at the expense of an increased risk of serious adverse events and asthma related mortality; risks which are not clearly abolished by inhaled corticosteroids. Therefore regular salmeterol should be discontinued if no symptomatic benefit is achieved and the manufacturers' advice not to increase the dose of salmeterol during exacerbations should be made clear. Salmeterol should not be used as a substitute for inhaled corticosteroids, and adherence with inhaled steroids should be kept under review if separate inhalers are used.
This is a Cochrane review abstract and plain language summary, prepared and maintained by The Cochrane Collaboration, currently published in The Cochrane Database of Systematic Reviews 2010 Issue 1, Copyright © 2010 The Cochrane Collaboration. Published by John Wiley and Sons, Ltd.. The full text of the review is available in The Cochrane Library (ISSN 1464-780X).
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July 16. 2008 AbstractBackgroundEpidemiological evidence has suggested a link between beta-agonists and increases in asthma mortality. There has been much debate about possible causal links for this association, and whether regular (daily) long-acting beta2-agonists are safe. ObjectivesThe aim of this review is to assess the risk of fatal and non-fatal serious adverse events in trials that randomised patients with chronic asthma to regular salmeterol versus placebo or regular short-acting beta2-agonists. Search strategyTrials were identified using the Cochrane Airways Group Specialised Register of trials. Web sites of clinical trial registers were checked for unpublished trial data and FDA submissions in relation to salmeterol were also checked. The date of the most recent search was August 2009. Selection criteriaControlled parallel design clinical trials on patients of any age and severity of asthma were included if they randomised patients to treatment with regular salmeterol and were of at least 12 weeks duration. Concomitant use of inhaled corticosteroids was allowed, as long as this was not part of the randomised treatment regimen. Data collection and analysisTwo authors independently selected trials for inclusion in the review. Outcome data were extracted by one author and checked by the second author. Unpublished data on mortality and serious adverse events were sought. Main resultsThe review includes 26 trials comparing salmeterol to placebo and 8 trials comparing with salbutamol. These included 62,815 participants with asthma (including 2,599 children). In 6 trials (2,766 patients), no serious adverse event data could be obtained. All cause mortality was higher with regular salmeterol than placebo but the increase was not significant, Peto Odds Ratio 1.33 (95% CI 0.85 to 2.08). Non-fatal serious adverse events were significantly increased when regular salmeterol was compared with placebo, Peto Odds Ratio 1.15 (95% CI 1.02 to 1.29). One extra serious adverse event occurred over 28 weeks for every 188 people treated with regular salmeterol [95% CI: 95 to 2606]. There is insufficient evidence to assess whether the risk in children is higher or lower than in adults. No significant increase in fatal or non-fatal serious adverse events was found when regular salmeterol was compared with regular salbutamol. Individual patient data from the SNS study have been combined with the results of the SMART study, as all the asthma-related deaths in adults occurred in these studies. In patients who were not taking inhaled corticosteroids, compared to regular salbutamol or placebo, there was a significant increase in risk of asthma-related death with regular salmeterol, Odds Ratio 9.52 (95% CI 1.24 to 73.09). The confidence interval for patients taking inhaled corticosteroids is too wide to rule in or out an increase in asthma mortality in this group. Authors' conclusionsIn comparison with placebo, we have found an increased risk of serious adverse events with regular salmeterol. There is also a clear increase in risk of asthma-related mortality in patients not using inhaled corticosteroids in the two large surveillance studies. Although the increase in asthma-related mortality was smaller in patients taking inhaled corticosteroids at baseline, the confidence interval is wide, so it cannot be concluded that the inhaled corticosteroids abolish the risks of regular salmeterol. The adverse effects of regular salmeterol in children remain uncertain due to the small number of children studied. |
