Long‐acting beta2‐agonists versus long‐acting muscarinic antagonists in patients with stable COPD: A systematic review and meta‐analysis of randomized controlled trials

Several long‐acting bronchodilators have been developed and are widely used as first‐line treatment in patients with stable chronic obstructive pulmonary disease (COPD). However, the initial choice of therapy is still uncertain. The aim of this study was to examine the clinical efficacy and safety of long‐acting muscarinic antagonist (LAMA) and long‐acting beta2‐agonist (LABA) in patients with stable COPD. We searched several databases and manufacturers’ websites to identify relevant randomized clinical trials for meta‐analysis. Outcomes of interest were trough forced expiratory volume in 1 s (FEV₁), acute exacerbations, transitional dyspnoea index (TDI) score, St George's Respiratory Questionnaire (SGRQ) score and adverse events. Sixteen trials with a total of 22 872 patients were included in this study. Compared with LABA, LAMA were associated with a greater reduction in acute exacerbations (OR: 0.84, 95% CI: 0.74–0.94, P = 0.003) and fewer adverse events (OR: 0.92, 95% CI: 0.86–0.97, P = 0.005). There were no significant differences in trough FEV₁, TDI and SGRQ scores. In patients with stable COPD, LAMA were associated with a greater reduction in acute exacerbations and fewer adverse effects compared with LABA.     

Long-acting Muscarinic Antagonist Versus Inhaled Corticosteroid when Added to Long-acting β-agonist for COPD: A Meta-analysis

The purpose of this study was to systematically review the efficacy and safety of long-acting β-agonist/long-acting muscarinic antagonist (LABA/LAMA) and LABA/inhaled corticosteroid (ICS) combinations in patients with advanced chronic obstructive pulmonary disease (COPD). Randomized clinical trials of at least 12 weeks of duration comparing LABA/LAMA and LABA/ICS combinations were included. We chose forced expiratory volume in 1 second (FEV¹), St. George's Respiratory Questionnaire (SGRQ) score, Transitional Dyspnea Index (TDI), COPD Assessment Test (CAT) score, COPD exacerbations, mortality, and other safety parameters as outcome assessment criteria. We included six randomized controlled trials with a total of 4,319 patients. Most patients did not have a history of exacerbation. LABA/LAMA was associated with greater improvement in FEV¹ than LABA/ICS (mean difference (MD) 0.09L, 95%confidence interval (CI) 0.07 to 0.11L; high certainty). Two treatments appeared clinically equivalent in improving SGRQ (MD ?0.12, 95%CI ?1.16 to 0.92; high certainty), TDI (MD 0.15, 95%CI ?0.05 to 0.35; high certainty), and CAT scores (MD 0.28 95%CI ?0.29 to 0.85; moderate certainty). LABA/LAMA was associated with an absolute reduction of approximately 8% in the incidence of pneumonia compared with LABA/ICS (risk ratio 0.41, 95%CI 0.18 to 0.94; moderate certainty). There was no significant difference in safety and exacerbation outcomes. However, equivalence of two treatments could not be concluded due to imprecision especially for mortality, cardiac serious adverse events, and severe exacerbations. Our findings support the use of dual long-acting bronchodilators for patients with advanced COPD but without frequent exacerbations given the excess risk of pneumonia with LABA/ICS.     

Tolerability of Bisoprolol on Domiciliary Spirometry in COPD

We investigated if serial domiciliary measures of spirometry were sensitive at detecting subtle effects of beta-2 blockade associated with bisoprolol in (n = 17) patients with COPD. After a two-week run in on inhaled corticosteroid (ICS) and long acting beta-2 agonist (LABA): beclometasone/formoterol 100/6 µg, patients’ started additional a long acting muscarinic receptor antagonist: (LAMA) Tiotropium 18 µg, with concomitant weekly dose titration of bisoprolol: 1.25–2.5–5 mg. After a further week of bisoprolol 5 mg, they were stepped back down to (ICS/LABA) for one week. Mean age was 64 years, mean FEV₁ 52% predicted, and mean FEV₁/FVC ratio of 0.46. Compared to baseline am FEV₁ of 1.38 L (95% CI 1.14–1.61 L), both ICS/LABA/LAMA and ICS/LABA in conjunction with bisoprolol showed statistically significant mean falls of 100 ml (1.28 L, 95% CI 1.03–1.53 L), and 120 ml, respectively (1.26 L, 95% CI 1.01–1.51 L); equalling and exceeding the MCID of 100 ml, respectively. These changes were disconnected from symptoms, reliever use and oxygen saturation.     

Switching from long‐acting beta‐agonist and inhaled corticosteroid to long‐acting beta‐agonist and long‐acting muscarinic antagonist for chronic obstructive pulmonary disease: a case report of inhaled corticosteroid withdrawal

Chronic obstructive pulmonary disease (COPD) is a medical condition characterised by persistent respiratory symptoms and airflow limitation. For the long‐term management of COPD, inhaled therapies are the main approach to maintenance treatment. In order to improve treatment efficacy and tolerability for patients with COPD, recent clinical trials have focused on the withdrawal of inhaled corticosteroids (ICSs), the use of which has been associated with adverse outcomes, including pneumonia. In this case report, a patient with Global Initiative for Chronic Obstructive Lung Disease grade 3 COPD was switched from a combined inhaled therapy of a long‐acting beta‐agonist (LABA) and ICS to a combination of a LABA and a long‐acting muscarinic antagonist (tiotropium/olodaterol) during hospitalisation for an acute exacerbation of COPD in April 2016. He was subsequently maintained in a stable condition, and was able to live and travel independently. This case report of successful ICS withdrawal suggests that, for moderate‐to‐severe COPD, if it is assessed individually, dual therapy of LABA and long‐acting muscarinic antagonist can be highly effective and well‐tolerated. Treatment compliance and lifestyle modifications have been shown to be critical in optimising treatment outcomes.     

Triple versus LAMA/LABA combination therapy for Japanese patients with COPD: A systematic review and meta-analysis

BackgroundIn symptomatic COPD patients with a history of exacerbations, additional treatment with inhaled corticosteroid (ICS) to long-acting muscarinic antagonist (LAMA) and long-acting beta-agonist (LABA) combination therapy is recommended based on the evidence of low incidence of exacerbations but with a caution for pneumonia. However, ethnic differences may affect the response to drugs. Therefore, we conducted a systematic review and meta-analysis to evaluate the efficacy and safety of this treatment in the Japanese population (PROSPERO: CRD42020191978).MethodsWe searched relevant randomized control trials and analyzed the exacerbations, quality of life, lung function, and adverse events including pneumonia and mortality as the outcomes of interest.ResultsWe identified a total of three RCTs (N = 632). Treatment with ICS/LAMA/LABA triple therapy significantly decreased the exacerbations (rate ratio, 0.56; 95% CI, 0.38 to 0.85) and improved the trough FEV₁ (mean difference, 0.04; 95% CI, 0.01 to 0.07) compared to LAMA/LABA therapy. However, triple therapy showed a significantly higher incidence of pneumonia compared to LAMA/LABA (odds ratio, 3.38; 95% CI, 1.58 to 7.22). Concerning other adverse events including mortality, there were no significant difference between these therapies.ConclusionsIn the current meta-analysis of the Japanese population, we confirmed that triple therapy causes a higher incidence of pneumonia than LAMA/LABA treatment but is a more preferable treatment since it showed a lower incidence of exacerbations and higher trough FEV₁ in patients with symptomatic moderate to severe COPD. However, since the sample sizes were not statistically large enough, further trials involving Japanese patients are needed.     

Patterns of use of long‐acting bronchodilators in patients with COPD: A nationwide follow‐up study of new users in New Zealand

Background and objective

While several studies have found that prescribing practices do not conform to chronic obstructive pulmonary disease (COPD) treatment guidelines, none have examined longitudinal patterns of use of long‐acting beta₂‐agonist (LABA) and long‐acting muscarinic antagonist (LAMA) therapy across an entire country. We undertook a nationwide follow‐up study to describe treatment patterns in new users of long‐acting bronchodilators.

Methods

National health and pharmaceutical dispensing data were used to identify patients aged ≥45 years who initiated LABA and/or LAMA therapy for COPD between 1 February 2006 and 31 December 2013. Dispensings of LABAs, LAMAs and inhaled corticosteroids (ICSs) were aggregated into episodes of use of therapeutic regimens. Kaplan–Meier curves, sunburst plots and sequence index plots were generated to summarize, respectively, the duration of the first regimen, the sequences in which unique regimens were used and the patterns of use and non‐use during follow‐up.

Results

The study cohort included 83 435 patients with 290 400 person‐years of follow‐up. The most commonly initiated regimen was a LABA with an ICS. ICS use was inconsistent with international guidelines: over‐ and under‐treatment occurred in patients with infrequent and frequent exacerbations, respectively, and ICS monotherapy was common. The median duration of the first regimen was 46 days. Many patients used multiple regimens over time and periods of non‐use were common.

Conclusion

In this nationwide study, patterns of use of LABAs, LAMAs and ICSs were complex and often did not comply with treatment guidelines. Further work is required to address the discrepancy between guidelines and prescribing practices.

     

Comparison of tiotropium plus formoterol to tiotropium alone in stable chronic obstructive pulmonary disease: a meta-analysis

Background and objective: It is not clear whether combination therapy with tiotropium plus formoterol has greater efficacy, without increasing the burden of adverse events, compared with tiotropium alone. This meta‐analysis was performed to evaluate the differences in efficacy and adverse events associated with combination therapy compared with tiotropium alone, in patients with stable COPD. Methods: MEDLINE, EMBASE, CINAHL and the Cochrane trials database were searched for this analysis. Randomized controlled trials of 2 or more weeks of treatment with tiotropium plus formoterol or arformoterol, compared with tiotropium alone, were reviewed. Studies were pooled to yield odds ratio (OR) or weighted mean differences (WMD), with 95% confidence interval (CI). Results: Eight trials, involving 1868 randomized patients, met the inclusion criteria. Treatment with tiotropium plus formoterol significantly improved the average FEV₁ (WMD 105 mL, 95% CI: 69–142), average FVC (WMD 135 mL, 95% CI: 96–174) and trough FEV₁ (WMD 53 mL, 95% CI: 30–76), compared with tiotropium alone, although the difference was not statistically significant for trough FVC. The mean change in transitional dyspnoea index (TDI) was markedly greater with tiotropium plus formoterol (WMD 1.50, 95% CI: 1.01–1.99) than with tiotropium alone, and there was a similar difference in the proportion of patients with a clinically significant change in TDI (OR 2.34, 95% CI: 1.58–3.46). There tended to be fewer adverse events and COPD exacerbations with tiotropium plus formoterol, compared with tiotropium alone, but the differences were not statistically significant. Conclusions: Tiotropium plus formoterol significantly improved lung function and symptom scores compared with tiotropium alone. There was a trend towards a reduction in adverse events, although the difference was not statistically significant. Long‐term trials are necessary to evaluate the effects of tiotropium plus formoterol and to clarify the role of combination therapy, compared with tiotropium alone.     

Comparison of three combined pharmacological approaches with tiotropium monotherapy in stable moderate to severe COPD: a systematic review

BackgroundGuidelines recommend the use of inhaled long-acting bronchodilators, inhaled corticosteroids (ICS) and their combinations for maintenance treatment of moderate to severe COPD. However, there are limited data supporting combination therapy.MethodsThis systematic review assessed the efficacy of three therapeutic approaches: tiotropium plus long-acting beta2-agonist (LABA) (“dual” therapy), LABA/ICS (“combined” therapy), and tiotropium plus LABA/ICS (“triple” therapy), all compared with tiotropium monotherapy. Randomized controlled trials were identified after a search of different databases of published and unpublished trials.ResultsTwenty trials (6803 participants) were included. “Dual” therapy showed significant improvements in forced volume in the first second (FEV₁), health-related quality of life (HRQoL), and dyspnea. However, it failed to reduce the risk of COPD exacerbations. Compared with tiotropium, “combined” therapy presented modest but significant effects on FEV₁, HRQoL, and dyspnea. Again, there was no significant difference in exacerbations, but it was associated with a significant increase of serious adverse effects (SAE) (number need to treat for harm [NNTH] = 20; 95% CI: 11–119). Finally, “triple therapy” increased FEV₁, improved HRQoL (both benefits exceeded minimal important differences) and decrease COPD exacerbations in anon-significant way. (Odds ratio [OR] = 0.57; 95% CI: 0.24 to 1.37, p = 0.21).Conclusions“Dual” and “triple” therapy seem like the most promising for patients with moderate to very severe COPD. However, data are still scarce and studies too short to generate a strong recommendation. Future studies should examine long-term efficacy and safety.     

Effectiveness of Treatment With Dual Bronchodilation (LABA/LAMA) Compared With Combination Therapy (LABA/ICS) for Patients With COPD: A Population-Based Study

BackgroundInitiation of treatment of COPD with a combination of a long-acting beta-agonist (LABA) and an inhaled corticosteroid (ICS) is frequent irrespective of the risk of exacerbations.MethodWe performed a retrospective, population-based, observational study aimed at comparing the effectiveness of a LABA/long-acting antimuscarinic agent (LAMA) and LABA/ICS in patients with COPD over a one-year follow-up. Data were obtained from an administrative healthcare claims database. The primary outcome was the risk of first exacerbation. A sensitivity analysis was conducted in a propensity-score matched population.ResultsThe population consisted of 14,046 COPD patients; 11,329 (80.6%) initiated LABA/ICS and 2717 (19.4%) LABA/LAMA. The matched population included 1650 patients in each arm. During follow-up, 69.6% patients in the LABA/ICS group and 64.4% in the LABA/LAMA group presented an exacerbation. The mean time to the first exacerbation was 6.03 months (95% confidence interval (CI): 5.94–6.12) for LABA/ICS and 6.4 months (95%CI: 6.21–6.59) for LABA/LAMA; p < 0.001. The time to scalation to triple therapy was also significantly prolonged in LABA/LAMA. Similar results were obtained in the matched population. LABA/LAMA was associated with a significantly lower risk of exacerbations and escalation to triple therapy compared to LABA/ICS, except in patients with frequent exacerbations and high blood eosinophils in which no differences were observed in the time to first exacerbation.ConclusionInitiation of treatment with LABA/LAMA was associated with a lower risk of exacerbation and escalation to triple therapy compared to LABA/ICS in the majority of patients with COPD in primary care.     

Treatment efficacy of LAMA versus placebo for stable chronic obstructive pulmonary disease: A systematic review and meta-analysis

BackgroundFour long-acting muscarinic antagonists (LAMAs), tiotropium, glycopyrronium, aclidinium, and umeclidinium, are currently available for the treatment of stable chronic obstructive pulmonary disease (COPD). However, no integrated analysis has sought to determine the effectiveness of these LAMAs. Thus, we conducted a systematic review and meta-analysis to evaluate the efficacy and safety of LAMA versus placebo in patients with stable COPD.MethodsA literature search of relevant randomized control trials that administered LAMA to stable COPD patients was conducted, and the exacerbations, quality of life (QoL), dyspnea score, lung function, and adverse event of patients were evaluated.ResultsA total of 33 studies were included in this meta-analysis. LAMA significantly decreased the frequency of exacerbations compared to the placebo (OR 0.75; 95% CI 0.66 to 0.85; P < 0.001). The mean changes in the St George's Respiratory Questionnaire score (mean difference, ?3.61; 95% CI, ?4.27 to ?2.95; P < 0.00001), transitional dyspnea index score (mean difference 1.00; 95% CI 0.83 to 1.17; P < 0.00001), and trough FEV₁ (mean difference 0.12; 95% CI 0.11 to 0.13; P < 0.0001) indicated significantly greater improvement in the LAMA group than the placebo group. The number of withdrawals due to adverse events in the LAMA group was significantly fewer than that in the placebo group (OR -0.02; 95% CI -0.03 to ?0.01; P = 0.002).ConclusionLAMA is superior to placebo due to lower frequency of exacerbations and adverse events, as well as higher trough FEV₁, QoL, and dyspnea score for stable COPD.     

Impact of Long-Acting Bronchodilators and Exposure to Inhaled Corticosteroids on Mortality in COPD: A Real-Life Retrospective Cohort Study

Introduction

We performed a real-life retrospective analysis to assess the impact of long-acting bronchodilator therapy and associated exposure to inhaled corticosteroids (ICS) on all-cause and cardiovascular mortality in patients with chronic obstructive pulmonary disease (COPD).

Methods

We used record linkage data from patients with a diagnosis of COPD in Tayside, Scotland, between 2001 and 2010. All-cause and cardiovascular mortality were assessed using Cox proportional hazard regression.

Results

A total of 4,133 patients were included, mean FEV₁ of 59.5 %, mean age of 68.9 years and mean follow-up of 4.6 years. There were 623 who were exposed to long-acting bronchodilators only and 3,510 to long-acting bronchodilators plus ICS. 1,372 patients (33 %) died during the study period. Compared with controls taking only long-acting bronchodilators either alone or in combination, all-cause mortality was reduced in patients taking long-acting muscarinic antagonist (LAMA) + ICS as dual therapy: adjusted hazard ratio 0.62 (95 % CI 0.45–0.85), but not by long-acting beta-agonist (LABA) + ICS: adjusted hazard ratio 1.02 (95 % CI 0.80–1.31). Cardiovascular mortality was not reduced by dual therapy with either LABA or LAMA and concomitant ICS exposure. All-cause and cardiovascular mortality were both reduced in patients taking triple therapy with LABA + LAMA + ICS: adjusted hazard ratio 0.51 (95 % CI 0.41–0.64) and 0.56 (95 % CI 0.35–0.90), respectively.

Conclusion

In patients exposed to ICS, concomitant use of LAMA alone as dual therapy or in combination with LABA as triple therapy were associated with reductions in all-cause mortality, while concomitant use of LABA without LAMA conferred no reduction. Moreover, only triple therapy was found to confer benefits on cardiovascular mortality.     

Indacaterol/glycopyrronium affects lung function and cardiovascular events in patients with chronic obstructive pulmonary diseases: A meta-analysis

BackgroundBronchodilators are the cornerstone for treating patients with chronic obstructive pulmonary diseases (COPD), although some studies have shown that dual bronchodilators may exacerbate incidence of adverse cardiovascular events. Here, we evaluated the cardiopulmonary safety of indacaterol/glycopyrronium (IND/GLY) using a meta-analysis.MethodsWe searched PubMed, OVID, Cochrane Library and Web of Science databases, using “indacaterol/glycopyrronium”, “indacaterol/glycopyrrolate”, “IND/GLY”, “QVA149”, “chronic obstructive pulmonary diseases”, “COPD”, “chronic obstructive airway disease”, “chronic obstructive lung disease” as key words. Acute exacerbation of COPD and FEV₁ as indicators of pulmonary function and occurrence of hypertension, atrial fibrillation, myocardial infarction and heart failure as indicators of cardiovascular safety.ResultsA total of 23 articles, comprising 21,238 participants, were included in the analysis. FEV₁ values were significantly different compared to IND/GLY and single bronchodilator therapy (LABA or LAMA), with the MD 0.11 L (95%CI: 0.10–0.13, P<0.01). Hypertension was more frequent in the IND/GLY, than the single bronchodilator therapy group, although this difference was insignificant (IND/GLY vs LABA, RR=1.88, P = 0.09; IND/GLY vs LAMA, RR=1.42, P = 0.08; IND/GLY vs LABA+ICS, RR=1.85, P = 0.23). In addition, IND/GLY did not significantly increase the risk of myocardial infarction (IND/GLY vs LAMA or double therapy, total RR: 1.49, 95%CI: 0.72–3.08, P = 0.28), atrial fibrillation (IND/GLY vs LAMA, RR: 1.62, 95%CI: 0.64–4.10, P = 0.31) and heart failure (IND/GLY vs LAMA, RR: 0.40, 95%CI: 0.07–2.33, P = 0.31) in COPD patients.ConclusionsIND/GLY significantly reduced incidence of acute COPD exacerbations, and slowed down the decline of FEV₁. Adequate safety measures are needed to control incidence of adverse cardiovascular events.     

The efficacy and safety of tiotropium in Chinese patients with stable chronic obstructive pulmonary disease: A meta-analysis

Background and objective: Tiotropium is the only long‐acting inhaled anticholinergic bronchodilator currently available in China, but information about its clinical effect in this population is limited. This meta‐analysis assessed the efficacy and safety of tiotropium in Chinese patients with stable COPD. Methods: An electronic search of the literature was undertaken to identify randomized controlled trials (RCTs) of tiotropium in Chinese patients, which were then assessed for inclusion in a meta‐analysis. The efficacy and safety of tiotropium was compared with placebo and ipratropium, using the outcomes of FEV₁, FEV₁%, symptoms, frequency of exacerbations, adverse events and safety. Results: Eleven RCTs recruiting 1006 patients were included in the meta‐analysis. Compared with both placebo and ipratropium, tiotropium significantly improved FEV₁[weighted mean difference (WMD) = 304 mL, 95% CI 271–337], FEV₁% (WMD = 8.35%, 95% CI 5.40–11.31) and symptoms [relative risk (RR) = 2.00, 95% CI 1.61–2.49]. Tiotropium significantly reduced the risk of exacerbations (RR = 0.07, 95% CI 0.01–0.54) compared with placebo, and there was a non‐significant reduction in the risk of exacerbations compared with ipratropium (RR = 0.70, 95% CI 0.13–3.75). Tiotropium was well tolerated with a similar safety profile to placebo and ipratropium (RR = 1.16, 95% CI 0.76–1.77, P = 0.49). Conclusions: Tiotropium improved pulmonary function and symptoms, reduced exacerbations and was well tolerated and safe. On the basis of its efficacy and safety profile, tiotropium appears to be a reasonable first‐line choice for the management of Chinese patients with stable COPD. Additional long‐term RCTs are required to further evaluate the efficacy and safety of tiotropium.     

Economic evaluation of treating chronic obstructive pulmonary disease with inhaled corticosteroids and long-acting beta2-agonists in a health maintenance organization

OBJECTIVES: In light of recent results from observational studies showing prolonged survival in subjects taking long-acting beta2-agonists (LABA) and/or inhaled corticosteroids (ICS) for chronic obstructive pulmonary disease (COPD), we investigated their cost-effectiveness (CE). METHODS: Costs and survival data were collected for a sample of members enrolled in a large Health Maintenance Organization in the United States. An observational study design was used to evaluate cumulative costs and health benefits of LABA, ICS, ICS+LABA, or comparison drugs. Survival was estimated using a parametric regression model. Costs were adjusted for censoring and prognostic factors. CE was evaluated over a time horizon of 36 months and the remaining lifetime of subjects. RESULTS: Over 36 months, life expectancy and costs were: 2.4 years (95% confidence interval (CI): 2.3; 2.5) and $28,030 (CI: $23,400; $33,570) for not receiving ICS or LABA; 2.6 years (CI: 2.6; 2.7) and $35,170 (CI: $29,970; $40,620) for ICS alone; 2.6 years (CI: 2.5; 2.7) and $27,380 (CI: $21,780; $32,510) for LABA alone; and, 2.7 years (CI: 2.6; 2.8) and $33,780 (CI: $28,700; $39,440) for subjects treated with ICS+LABA. The lifetime analysis showed similar trends. CONCLUSIONS: There is an acute need to find effective, life-extending treatments for persons with COPD. ICS, LABA or their combination represent promising treatment options and are currently being tested in randomized trials. If the impact on survival seen in these trials compares to that seen in observational studies, LABA and the combination treatment are likely to be cost-effective in the United States.     

Efficacy and Safety of an Aclidinium Bromide Treatment for 12 Weeks or Longer in Patients with Moderate-To-Severe COPD: A Meta-Analysis

Background: Bronchodilators are commonly used to manage patients with stable chronic obstructive pulmonary disease (COPD). This meta-analysis assessed the efficacy of aclidinium bromide with respect to clinical events, health-related quality of life and symptom scales, pulmonary function, and safety among patients with stable COPD. Methods: A comprehensive search of MEDLINE, EMBASE, CINAHL and the Cochrane Library databases was undertaken to identify randomized controlled trials (RCTs) that compared aclidinium with placebo, treatment over at least 12 weeks. Trials were measured using either odds ratios (OR) or mean differences (MD) with 95% confidence intervals (CI). Results: Seven studies, containing 7001 patients, were included in this meta-analysis. Compared with placebo, aclidinium bromide reduced the incidence of exacerbation-related hospitalizations (OR 0.64; 95% CI 0.47 to 0.89) and improved quality of life as measured by a lower total George's Respiratory Questionnaire [SGRQ] score (MD ?2.34; 95% CI ?3.18 to ?1.51) and attenuated dyspnea symptom as assessed by changes in the Transitional Dyspnea Index [TDI] (MD 0.76; 95% CI 0.43 to 1.10). Similar changes were observed with regard to trough FEV₁ and FVC and peak FEV₁ and FVC. No significant differences were observed with regard to all-cause mortality, COPD exacerbations, non-fatal serious adverse events or cardiac adverse events. Conclusions: Aclidinium reduced the incidence of exacerbation-related hospitalizations and improved quality of life, COPD symptoms and pulmonary function. In addition, aclidinium did not increase the incidence of non-fatal serious adverse events, cardiac adverse events, or COPD exacerbations and was not associated with increased mortality.     

Emergency Hospital Care for Exacerbation of COPD: Is Inhaled Maintenance Therapy Modified?

Background: The impact of hospital emergency care and inward admission for acute exacerbations of COPD on inhaled maintenance treatment is not well known. Objective: Therefore, we evaluated the impact of short-stay emergency hospital care and inward admission for acute exacerbation of COPD (eCOPD) on inhaled maintenance treatment prescribed at discharge. Design: Prospective observational cohort study of patients presenting with eCOPD at emergency departments in 16 hospitals of the Spanish healthcare system. The ethics committee at each hospital approved the study and patients provided an informed consent before inclusion. We classified the patients according to the severity of COPD: mild/moderate (FEV₁ ≥ 50% predicted) or severe/very severe (FEV₁ < 50% predicted) and need of inward hospitalisation. We analysed changes to maintenance treatment on discharge according to GOLD strategy. Results: 1559 patients, 65% required hospitalisation. The most common maintenance treatment was inhaled corticoids (ICS) (80.9%) followed by long-acting beta-agonists (LABA) (75.4%). The most common combination was triple therapy (LABA+ LAMA+ICS) (56.2%) followed by LABA+ICS dual therapy (18.2%) regardless of the severity of COPD. In more than 60% of patients treatment was not changed at discharge. The most common change in treatment was a reduction when discharge was from emergency care and an increase after hospitalisation (-21.6% and +19.5% in severe/very severe COPD, respectively). Conclusions: Emergency hospital care for eCOPD does not usually induce changes in inhaled maintenance treatment for COPD regardless of the duration of the hospital stay.     

The safety of long‐acting beta‐agonists: More evidence is needed

There is controversy regarding the possibility that long‐acting beta‐agonists (LABA) may paradoxically contribute adversely to asthma mortality. While studies and meta‐analyses indicate increased risk, epidemiological data indicate a slow fall in asthma mortality since the introduction of LABA. Advocates for LABA propose that mandatory simultaneous use of inhaled corticosteroids satisfactorily reduce any potential risk. In the face of lingering doubts, others propose that LABA should be withdrawn from use. In this pro–con article, Kazani et al. provide the rationale for a modified randomized controlled trial that would define the level of risk more clearly, and provide the basis for a clear judgment to be made. Sears argues that current knowledge about the risks associated with LABA, especially when prescribed as monotherapy, provides sufficient evidence for clinicians and licensing authorities alike, and that the logistics and likely outcomes for a large prospective study are unjustified.     

Fixed‐dose combination of umeclidinium and vilanterol for patients with chronic obstructive pulmonary disease: A systematic review

Chronic obstructive pulmonary disease (COPD) is a common respiratory disease that is predicted to be one of the leading causes of death worldwide. Pharmacologic treatment options of COPD are bronchodilators, using either long‐acting β2‐agonists (LABAs), or long‐acting muscarinic antagonists (LAMAs), or a combination of two. Anoro Ellipta (umeclidinium + vilanterol) dry powder inhaler, a fixed‐dose combination of LAMA and LABA, was Food and Drug Administration (FDA) approved in 2013 for COPD. The objective of this study is to evaluate the efficacy and safety of once daily umeclidinium/vilanterol (62.5 mcg/25 mcg) in COPD patients, focusing on pharmacodynamic and pharmacokinetic characteristics, efficacy and safety in clinical studies and cost. Literature search was done through PubMed (2004‐2017) using the terms umeclidinium, vilanterol, COPD, LABA and LAMA. Recent and significant clinical trials about the monocomponents and their combination were identified, in addition to reviews, guidelines for COPD, data from manufacturer and FDA product labels. The search was limited to English language studies on human subjects. Clinical data published on the combination of umeclidinium/vilanterol in patients with COPD have shown greater improvements in lung function compared to monotherapies. However, further studies comparing umeclidinium/vilanterol FDC (ANORO) to other LABA/LAMA combinations are needed.     

Missing Potential Opportunities to Reduce Repeat COPD Exacerbations

Introduction

Long-acting beta-agonists (LABA) and/or inhaled corticosteroids (ICS) have been shown to reduce COPD exacerbation risk. Using data from a large integrated health-care system, we sought to examine whether these medication classes were initiated after an exacerbation of COPD.

Methods

We identified patients who experienced an inpatient or outpatient COPD exacerbation within the Veterans Affairs Integrated Service Network (VISN)-20. We assessed the addition of a new inhaled therapy (an ICS, LABA or both) within 180 days after the exacerbation. We assessed independent predictors of adding treatment using logistic regression.

Results

We identified 45,780 patients with COPD, of whom 2,760 patients experienced an exacerbation of COPD. Of these individuals, 2,570 (93.1 %) were on either none or only one long-acting medication studied (LABA or ICS). In the subsequent 180-day period after their exacerbation, only 875 (34.1 %) patients had at least one of these additional therapies dispensed from a VA pharmacy. Among patients who were treated in the outpatient setting, older age [OR 0.98/year, 95 % CI (0.97–0.99)], current tobacco use [OR 0.74, 95 % CI (0.60–0.90)], greater use of ipratropium bromide [OR 0.97/canister, 95 % CI (0.96–0.98)], prior COPD exacerbation [OR 0.55, 95 % CI (0.46–0.67)], depression [OR 0.77, 95 % CI (0.61–0.98)], CHF [OR 0.74, 95 % CI (0.57–0.97)], and diabetes (OR 0.77 (0.60–0.99)] were associated with lower odds of additional therapy. Patients who were treated in the hospital had similar associated predictors.

Conclusion

Among patients treated for an exacerbation of COPD, we found relatively few were subsequently prescribed inhaled therapies known to reduce exacerbations.