1. 1 Once-daily indacaterol versus twice-daily salmeterol for COPD ; a placebo-controlled comparison R2 정명화 Eur Respir J 2011; 37: 273–279

2. 2 *Backgroun d* COPD : 10% of the world’s population aged 40. Long-acting inhaled bronchodilators is recommended element in managing the symptoms of patients with COPD. Twice daily (Beta 2-agonists formoterol and salmeterol) or once daily (the anticholinergic tiotropium) are recommanded. Indacaterol : ultra-long-acting b2-agonist bronchodilator 24-h efficacy,maintenance treatment.

3. 3 *Method* Patients 142 centers in 15 countries, between November 2007 and January 2009. Males and females aged 40 yrs with a clinical diagnosis of moderate-to-severe COPD and a smoking history of >20 pack- yrs were enrolled in the study. FEV1 : 30% ~ 80% Predicted. FeV1/ FVC < 0.7, measured within 30 min of inhaling 400 mg salbutamol Patients with a history of asthma. 3 3

4. 4 Study design *Method* Patients were randomised to receive double-blind. 1) Indacaterol (150 ug once daily via single-dose dry-powder inhaler, morning) 2) Salmeterol (50 ug twice daily -morning and evening- via inhaler) or placebo for 26 weeks. Patients were permitted concomitant medication with inhaled corticosteroids (ICS), if dose and regimen were stable for 1 month Patients with ICS and long-acting b2-agonist were switched to the equivalent ICS monotherapy Salbutamol was provided for use as needed (but not,6 h before study assessments). 4

5. 5 Assessments *Method* The primary objective was to confirm the superiority of 150 mg indacaterol over placebo with respect to 24-h post-dose ‘‘trough’’ FEV1 after day 2, 12,26weeks. Secondary objectives were to compare the effect of indacaterol versus salmeterol and salmeterol versus placebo on trough FEV1 after day 2, 12,26weeks. Health status was assessed by St George’s Respiratory questionnaire (SGRQ) at weeks 4, 8, 12 and 26. Dyspnea was assessed by Transition dyspnea index (TDI) and at weeks 4, 8, 12 and 26. 5

6. 6 Assessments *Method* Patients recorded their symptoms, pretreatment, peak expiratory flow (PEF) morning and evening, use of as- needed salbutamol ‘‘days of poor COPD control’’ was based on an end-point (score >=2 on a 0–3 scale, 2 of cough, wheeze, production/colour of sputum and breathlessness. ) The effect of indacaterol relative to placebo on SGRQ score at week12 and on percentage days of poor COPD control were predefined important secondary end-point Adverse effect : vital signs,ECGs,QT interval, Blood samples (K, Glucose ), any event 6

7. 7 Statistical analysis *Method* Patients: randomly 1:1:1 ratio (with stratification for smoking status) using an automated system ANCOVA was used to analized Efficacy variables 7

8. 8 *RESULT*

9. 9 9 Disposition of Pt.

10. 10 Patient characteristics

11. 11 Spirometry

12. 12 Symptom change

13. 13 Symptom change SGRQ score <, = -4

14. 14 Symptom change

15. 15 Symptom change * TDI increases >= 1* Placebo 39.5–45.7% Salmeterol 48.7–53.6% Indacaterol 56.6–60.5% 2.26 1.71 2.79 1.87 2.13 1.90

16. 16 Safety 8.8,% 5.7% 7.8%Serious adverse events Cough after inhalation17.6,% 0.9% 2.5%

17. 17 *Discussion* Once daily b2-agonist >twice-daily b2-agonist > more frequently dose short-acting bronchodilator 150ug once indacaterol >12 h after salmeterol (FeV1, morning PEF,SGRQ,TDI, decrease using of salbutamol), during the 6- month period. Indacaterol is similar to provided by once-daily tiotropium. Safety and tolerability were similar across the treatment groups. infections and infestations : Indacaterol 300~600ug > indacaterol 150ug Cough following inhalation was fairly common, but did not appear troublesome 17

18. 18 *Conclusion* This comparative studies show that indacaterol is a more effective bronchodilator than salmeterol 18