The effects of long-acting bronchodilators on total mortality in patients with stable chronic obstructive pulmonary disease

Abstract

BackgroundChronic obstructive pulmonary disease (COPD) is the 4th leading cause of mortality worldwide. Long-acting bronchodilators are considered first line therapies for patients with COPD but their effects on mortality are not well known. We performed a comprehensive systematic review and meta-analysis to evaluate the effects of long-acting bronchodilators on total mortality in stable COPD.MethodsUsing MEDLINE, EMBASE and Cochrane Systematic Review databases, we identified high quality randomized controlled trials of tiotropium, formoterol, salmeterol, formoterol/budesonide or salmeterol/fluticasone in COPD that had a follow-up of 6 months or longer and reported on total mortality. Two reviewers independently abstracted data from the original trials and disagreements were resolved by iteration and consensus.ResultsTwenty-seven trials that included 30,495 patients were included in the review. Relative risk (RR) for total mortality was calculated for each of the study and pooled together using a random-effects model. The combination of inhaled corticosteroid (ICS) and long-acting beta-2 agonist (LABA) therapy was associated with reduced total mortality compared with placebo (RR, 0.80; p = 0.005). Neither tiotropium (RR, 1.08; p = 0.61) nor LABA by itself (RR, 0.90; p = 0.21) was associated with mortality.ConclusionsA combination of ICS and LABA reduced mortality by approximately 20%. Neither tiotropium nor LABA by itself modifies all-cause mortality in COPD.

Tratamento farmacológico da DPOC

“…The first meta-analysis compared the use of LABAs in isolation with the use of LABA-IC combinations and found that the addition of ICs to the habitual therapy did not reduce mortality. (51) The second (72) concluded that only LABA-IC combinations had a beneficial effect on mortality, and that effect was small (relative risk = 0.80 [95% CI: 0.69-0.94]), a result that remained consistent even after the exclusion of patients investigated in another study included in the meta-analysis. (34) Of the 22 articles analyzed in the present systematic review, only 7 demonstrated beneficial effects on mortality.…”

From the authors

“…The present systematic review is limited by the paucity of data on budesonide, in a similar manner to our previous analysis on the outcome of pneumonia [2]. However, the subsequent availability of data on budesonide allowed us to conduct appropriate intention to treat meta-analysis on pneumonia, without censoring participants [3]. This analysis demonstrated no conclusive differences between inhaled fluticasone and budesonide on the risk of pneumonia.…”

“…In contrast, the use of HRT was driven largely by observational studies [5] and colecoxib by short-term (,6 month) clinical trials powered on (arthritic) symptom-based end-points, rather than hard outcomes such as mortality [6]. Thus, the comparison of ICS with these two drugs is unfair and needlessly raises anxiety over the safety of ICS, which when used appropriately are safe [3]. Secondly, M.A.…”

“…[1,2]. In combination with long-acting b 2 -agonists (LABAs), ICS further reduce exacerbations and enhance quality of life of patients with COPD and may even reduce mortality [3,4]. In contrast, the use of HRT was driven largely by observational studies [5] and colecoxib by short-term (,6 month) clinical trials powered on (arthritic) symptom-based end-points, rather than hard outcomes such as mortality [6].…”

Chronic Obstructive Pulmonary Disease in Primary Care - From Diagnosis to Therapy

“…In severe cases the only fixed combination of LABA and ICS, given twice a day and for several years, has also been shown to reduce mortality compared to placebo (Baker et al, 2009;Kliber et al, 2010;Nannini et al, 2007a;Wilt et al, 2007). However, the benefit is very modest, so that combination therapy (LABA + ICS, with or without tiotropium) does not appear to significantly improve clinically important outcomes (such as mortality, hospitalizations, severe exacerbations) than treatment with single products (Baker et al, 2009;Kliber et al, 2010;Nannini et al, 2007b;Puhan et al, 2009;Rodrigo et al, 2009;Welsh et al, 2010;Wilt et al, 2007). The association between LABA and tiotropium does not demonstrate advantages when compared with tiotropium alone (Wang et al, 2011).…”