Dovepress Long-acting β-adrenoceptor agonists and COPD 300 mcg once daily versus placebo and comparator drugs and performance or participation in single or multi-centre salmeterol, formoterol, and tiotropium using Antiplatelet clinical trials in 2004-2011 from various companies (Alm- Trialists’ Collaboration criteria for cardio-/cerebrovascular irall, Altana, AstraZeneca, Boehringer Ingelheim, Cytos, adverse events. Safety data were pooled from three clinical Novartis, GSK, Revotar Biopharmaceuticals, EpiGenesis, trials.39,43,45 The risk of cardio-/cerebrovascular events was not Corus Pharma, Merck Sharp & Dohme, Fujisawa, Pfizer, significantly increased for indacaterol at both doses versus Medapharma). JB and KMB have received compensations placebo, and the incidence of notable QTc interval changes for serving on advisory boards for AstraZeneca, Almirall, (.60 ms versus baseline) was low with all treatments. In a Cytos, Boehringer Ingelheim, Novartis, and Revotar AG subgroup of patients analyzed by Holter monitoring, there from 2006–2011. was no relevant effect of indacaterol versus placebo on the development of arrhythmias. Mortality was numerically lower with all active treatments than with placebo, with a 70% lower relative risk with indacaterol at both doses versus placebo (P = 0.054). In light of the approved recommended dose of 150 mcg and a maximal recommended dose of 300 mcg once daily, the overall safety data indicate a favorable tolerability profile and a broad therapeutic window for indacaterol. Summary Bronchodilators are the cornerstone of treatment for all COPD severity stages, with a central role in the symptomatic management of COPD. They are given on an as-needed basis or on a regular basis to prevent or reduce symptoms and exacerbations. The principal inhaled bronchodilator treat- ments are β(2)-agonists and anticholinergics, used alone or in combination. There is broad evidence that regular treatment with long-acting bronchodilators is more effective and conve- nient than treatment with short-acting bronchodilators. New data from trials with the novel once-daily β(2)-agonist inda- caterol indicate superior bronchodilation and clinical efficacy over twice-daily LABAs salmeterol and formoterol and at least equipotent bronchodilation as once-daily tiotropium. Therapeutic developments in COPD indicate a change shift from short-acting bronchodilators with multiple dosings per day to reduced dosing frequency and prolonged duration of action, including once-daily treatment. Disclosure JB and KMB have both participated as speakers in scientific meetings or courses organized and financed by various phar- maceutical companies (AstraZeneca, Almirall, GSK, Boeh- ringer, Novartis, Pfizer, Takeda) in 2006-2011. JB and KMB have also been reimbursed for travel expenses for attending and presenting at scientific conferences by various pharma- ceutical companies. The institution where JB and KMB are currently employed has received reimbursement for design International Journal of COPD 2011:6 References 1. Global Initiative for Chronic Obstructive Lung Disease. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: 2008 update. http://www.goldcopd.com/. Accessed March 21, 2011. 2. Sin DD, MacAlister FA, Man SFP, Anthonisen NR. Contemporary management of chronic obstructive pulmonary disease. JAMA. 2003; 290:2301–2312. 3. Tashkin DP, Cooper CB. The role of long-acting bronchodilators in the management of stable COPD. Chest. 2004;125:249–259. 4. Decramer M, Celli B, Kesten S, et al. Effect of tiotropium on outcomes in patients with moderate chronic obstructive pulmonary disease (UPLIFT): a prespecified subgroup analysis of a randomised controlled trial. Lancet. 2009;374:1171–1178. 5. Celli B, Decramer M, Kesten S, et al. Mortality in the 4-year trial of tiotropium (UPLIFT) in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2009;180:948–955. 6. Bourbeau J, Bartlett SJ. Patient adherence in COPD. Thorax. 2008;63: 831–838. 7. Vestbo J, Anderson JA, Calverley PMA, et al. Adherence to inhaled therapy, mortality and hospital admission in COPD. Thorax. 2009;64: 939–943. 8. Cazzola M, Santangelo G, Piccolo A, et al. Effect of salmeterol and formoterol in patients with chronic obstructive pulmonary disease. Pulm Pharmacol. 1994;7:103–107. 9. Cazzola M, Matera MG, Santangelo G, et al. Salmeterol and formoterol in partially reversible severe chronic obstructive pulmonary disease: a dose-response study. Respir Med. 1995;89:357–362. 10. Dahl R, Greefhorst LA, Nowak D, et al. Inhaled formoterol dry powder versus ipratropium bromide in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2001;164:778–784. 11. Matera MG, Cazzola M, Vinciguerra A, et al. A comparison of the bronchodilating effects of salmeterol, salbutamol and ipratropium bromide in patients with chronic obstructive pulmonary disease. Pulm Pharmacol. 1995;8:267–271. 12. Mahler DA, Donohue JF, Barbee RA, et al. Efficacy of salmeterol xinafoate in the treatment of COPD. Chest. 1999;115:957–965. 13. Rennard SI, Anderson W, ZuWallack R, et al. Use of a long-acting inhaled beta2-adrenergic agonist, salmeterol xinafoate, in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2001;163:1087–1092. 14. Cote C, Pearle JL, Sharafkhaneh A, Spangenthal S. Faster onset of action of formoterol versus salmeterol in patients with chronic obstructive pulmonary disease: a multicenter, randomized study. Pulm Pharmacol Ther. 2009;22:44. 15. Bouros D, Kottakis J, Le Gros V, et al. Effects of formoterol and salmeterol on resting inspiratory capacity in COPD patients with poor FEV(1) reversibility. Curr Med Res Op. 2004;20:581–586. 16. Celik G, Kayacan O, Beder S, Durmaz G. Formoterol and salmeterol in partially reversible chronic obstructive pulmonary disease: a cross- over, placebo-controlled comparison of onset and duration of action. Respiration. 1999;66:434–439. submit your manuscript | www.dovepress.com Dovepress 241