Tools for Practice

#66 Which is the best puffer for initial therapy in COPD?

Which puffer has the greatest impact on clinical outcomes as the first-line long-acting inhaled treatment for COPD?

Tiotropium (or other LAMA) +/- LABA is the best initial long-acting therapy for COPD, followed by a LABA (like salmeterol). Despite widespread use, inhaled steroids increase pneumonia risk and provide little if any benefit in COPD.

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Long-acting antimuscarinic agents (LAMA) versus long-acting beta agonists (LABA) 
  • Cochrane review1 of seven Randomized Controlled Trials (RCTs) of 12,123 patients comparing tiotropium to LABA (formoterol, indacaterol, salmeterol) over 3-12 months. 
    • More patients exacerbation-free with tiotropium72.7% versus 70.5% with LABANumber Needed to Treat (NNT)=46. 
  • INVIGORATE:2 One year RCT (3,444 patients) randomized to tiotropium 18 mcg or indacaterol 150 mcg, each once daily. 
    • More patients exacerbation-free with tiotropium: 65% versus 60% with indacaterol, NNT=20. 
  • No difference in mortality or quality of life.1,2 
LAMA versus LABA plus steroid: 
  • INSPIRE:3 Two year trial (1,323 patients) comparing tiotropium 18 mcg daily to salmeterol/fluticasone 50/500 mcg BID. 
    • No difference in exacerbations, and no clinical difference in quality of life. 
    • While there were differences in some secondary outcomes, drop-out was high (39%) and no outcome data was collected on drop-outs. 
      • Cochrane reviewers4 felt the results were unreliable. 
LAMA + LABA versus LABA plus steroid: 
  • FLAME:5 One year RCT (3,362 patients) comparing indacaterol/glycopyrronium 110/50 mcg once daily versus salmeterol/fluticasone 50/500 mcg BID. 
    • LAMA/LABA versus LABA/steroid had lower: 
      • Exacerbation rate 0.88 (0.82-0.94). 
      • Risk of pneumonia: 3.2% versus 4.8%, NNT=63. 
    • No difference in mortality and no clinical difference in quality of life. 
  • Meta-analysis of eight trials (4,392 patients) showed similar results.6 
LABA versus steroid: 
  • Cochrane review7 (seven studies, 5,997 patients). 
    • No difference in exacerbations and no clinical difference in quality of life. 
    • Steroids caused more pneumonia, and possibly increased mortality (odds ratio 1.17, 95% CI 0.97-1.42).
  • Most trials above were industry funded, generally favoring the sponsor’s drug. 
  • Inhaled steroids increase the risk of pneumonia8 [Number Needed to Harm (NNH)=44] and fractures9 (NNH=83).   
  • Guidelines,10 written before many of these trials were published, recommend tiotropium or LABA as initial therapy. 
updated July 26 2016 by Ricky

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  • G. Michael Allan MD CCFP
  • James McCormack BSc(Pharm) PharmD

1. Chong J, Karner C, Poole P. Cochrane Database Syst Rev. 2012; 9:CD009157.

2. Decramer ML, Chapman KR, Dahl R, et al. Lancet Respir Med. 2013; 1:524-33.

3. Wedzicha JA, Calverley PM, Seemungal TA, et al. Am J Respir Crit Care Med. 2008; 177:19-26.

4. Welsh EJ, Cates CJ, Poole P. Cochrane Database Syst Rev. 2013; 5:CD007891.

5. Wedzicha JA, Banerji D, Chapman KR, et al. N Engl J Med. 2016; 374:2222-34.

6. Horita N, Miyazawa N, Tomaru K, et al. Respirology. 2015; 20:1153-9.

7. Spencer S, Karner C, Cates CJ, et al. Cochrane Database Syst Rev. 2011; 12:CD007033.

8. Festic E, Bansal V, Gupta E, et al. COPD. 2016; 13:312-26.

9. Loke YK, Cavallazzi R, Singh S. Thorax. 2011; 66:699-708.

10. Qaseem A, Wilt TJ, Weinberger SE, et al. Ann Intern Med. 2011; 155:179-91.

Authors do not have any conflicts of interest to declare.