Regular treatment with salmeterol for chronic asthma: serious adverse events

Abstract

Background-Epidemiological evidence has suggested a link between beta 2-agonists and increases in asthma mortality. There has been much debate about possible causal links for this association, and whether regular (daily) long-acting beta 2-agonists are safe. Objectives-The 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 beta 2-agonists. Search methods-We identified trials using the Cochrane Airways Group Specialised Register of trials. We checked websites of clinical trial registers for unpublished trial data and FDA submissions in relation to salmeterol. The date of the most recent search was August 2011. Selection criteria-We included controlled parallel design clinical trials on patients of any age and severity of asthma 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 analysis-Two authors independently selected trials for inclusion in the review. One author extracted outcome data and the second checked them. We sought unpublished data on mortality and serious adverse events.

Meta-analysis of the risk of mortality with salmeterol and the effect of concomitant inhaled corticosteroid therapy

“…While the lack of a statistically significant increase in asthma mortality with salmeterol and ICS therapy provides some reassurance, the analysis lacked statistical power to rule out important associations. This interpretation is consistent with that of the recent Cochrane review16 in which unpublished SNS data were obtained from GSK on the use of ICS at baseline for each of the asthma-related deaths and the proportion of subjects taking baseline ICS. This enabled a combined analysis of the risk of asthma mortality with salmeterol in association with ICS use from the SNS and SMART studies.…”

Meta-analysis of the risk of mortality with salmeterol and the effect of concomitant inhaled corticosteroid therapy

“…While the lack of a statistically significant increase in asthma mortality with salmeterol and ICS therapy provides some reassurance, the analysis lacked statistical power to rule out important associations. This interpretation is consistent with that of the recent Cochrane review16 in which unpublished SNS data were obtained from GSK on the use of ICS at baseline for each of the asthma-related deaths and the proportion of subjects taking baseline ICS. This enabled a combined analysis of the risk of asthma mortality with salmeterol in association with ICS use from the SNS and SMART studies.…”

Regular treatment with formoterol for chronic asthma: serious adverse events

“…The findings of this review are similar to those of our review comparing regular salmeterol to placebo and regular salbutamol (Cates 2008). Both reviews show that, in comparison with placebo, there are significant increases in all-cause SAEs with the use of regular long-acting beta 2 -agonists.…”

Serious Asthma Events with Fluticasone plus Salmeterol versus Fluticasone Alone

“…23 Studies and reviews that have evaluated the safety of SABAs and LABAs have included a discussion of possible causes of the observed increase in the risk of asthma-related death and have noted a concern about whether the risk was greater among specific age or racial groups. 1,8,10,[18][19][20][24][25][26] Data from our trial do not support hypotheses that specific age or racial groups are at greater risk when beta-agonists are used concurrently with inhaled glucocorticoids.…”

Meta-analysis of the risk of mortality with salmeterol and the effect of concomitant inhaled corticosteroid therapy

“…While the lack of a statistically significant increase in asthma mortality with salmeterol and ICS therapy provides some reassurance, the analysis lacked statistical power to rule out important associations. This interpretation is consistent with that of the recent Cochrane review16 in which unpublished SNS data were obtained from GSK on the use of ICS at baseline for each of the asthma-related deaths and the proportion of subjects taking baseline ICS. This enabled a combined analysis of the risk of asthma mortality with salmeterol in association with ICS use from the SNS and SMART studies.…”

Regular treatment with formoterol for chronic asthma: serious adverse events

“…The findings of this review are similar to those of our review comparing regular salmeterol to placebo and regular salbutamol (Cates 2008). Both reviews show that, in comparison with placebo, there are significant increases in all-cause SAEs with the use of regular long-acting beta 2 -agonists.…”

Serious Asthma Events with Fluticasone plus Salmeterol versus Fluticasone Alone

“…23 Studies and reviews that have evaluated the safety of SABAs and LABAs have included a discussion of possible causes of the observed increase in the risk of asthma-related death and have noted a concern about whether the risk was greater among specific age or racial groups. 1,8,10,[18][19][20][24][25][26] Data from our trial do not support hypotheses that specific age or racial groups are at greater risk when beta-agonists are used concurrently with inhaled glucocorticoids.…”

Meta-analysis of the risk of mortality with salmeterol and the effect of concomitant inhaled corticosteroid therapy

“…While the lack of a statistically significant increase in asthma mortality with salmeterol and ICS therapy provides some reassurance, the analysis lacked statistical power to rule out important associations. This interpretation is consistent with that of the recent Cochrane review16 in which unpublished SNS data were obtained from GSK on the use of ICS at baseline for each of the asthma-related deaths and the proportion of subjects taking baseline ICS. This enabled a combined analysis of the risk of asthma mortality with salmeterol in association with ICS use from the SNS and SMART studies.…”

Regular treatment with formoterol for chronic asthma: serious adverse events

“…The findings of this review are similar to those of our review comparing regular salmeterol to placebo and regular salbutamol (Cates 2008). Both reviews show that, in comparison with placebo, there are significant increases in all-cause SAEs with the use of regular long-acting beta 2 -agonists.…”

Serious Asthma Events with Fluticasone plus Salmeterol versus Fluticasone Alone

“…23 Studies and reviews that have evaluated the safety of SABAs and LABAs have included a discussion of possible causes of the observed increase in the risk of asthma-related death and have noted a concern about whether the risk was greater among specific age or racial groups. 1,8,10,[18][19][20][24][25][26] Data from our trial do not support hypotheses that specific age or racial groups are at greater risk when beta-agonists are used concurrently with inhaled glucocorticoids.…”