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Respiratory medicine
Research
Comparative safety and effectiveness of long-acting inhaled agents for treating chronic obstructive pulmonary disease: a systematic review and network meta-analysis
  1. Andrea C Tricco1,2,
  2. Lisa Strifler1,
  3. Areti-Angeliki Veroniki1,
  4. Fatemeh Yazdi3,
  5. Paul A Khan1,
  6. Alistair Scott1,
  7. Carmen Ng1,
  8. Jesmin Antony1,
  9. Kelly Mrklas1,4,
  10. Jennifer D'Souza1,
  11. Roberta Cardoso1,
  12. Sharon E Straus1,5
  1. 1Knowledge Translation Program, Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, Ontario, Canada
  2. 2Epidemiology Division, Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada
  3. 3Ottawa Hospital Research Institute, Center for Practice Changing Research Building, The Ottawa Hospital-General Campus, Ottawa, Ontario, Canada
  4. 4Alberta Health Services, Edmonton, Alberta, Canada
  5. 5Department of Geriatric Medicine, University of Toronto, 27 Kings College Circle, Toronto, Ontario, Canada
  1. Correspondence to Dr Sharon E Straus; sharon.straus{at}utoronto.ca

Abstract

Objective To compare the safety and effectiveness of long-acting β-antagonists (LABA), long-acting antimuscarinic agents (LAMA) and inhaled corticosteroids (ICS) for managing chronic obstructive pulmonary disease (COPD).

Setting Systematic review and network meta-analysis (NMA).

Participants 208 randomised clinical trials (RCTs) including 134 692 adults with COPD.

Interventions LABA, LAMA and/or ICS, alone or in combination, versus each other or placebo.

Primary and secondary outcomes The proportion of patients with moderate-to-severe exacerbations. The number of patients experiencing mortality, pneumonia, serious arrhythmia and cardiovascular-related mortality (CVM) were secondary outcomes.

Results NMA was conducted including 20 RCTs for moderate-to-severe exacerbations for 26 141 patients with an exacerbation in the past year. 32 treatments were effective versus placebo including: tiotropium, budesonide/formoterol, salmeterol, indacaterol, fluticasone/salmeterol, indacaterol/glycopyrronium, tiotropium/fluticasone/salmeterol and tiotropium/budesonide/formoterol. Tiotropium/budesonide/formoterol was most effective (99.2% probability of being the most effective according to the Surface Under the Cumulative RAnking (SUCRA) curve). NMA was conducted on mortality (88 RCTs, 97 526 patients); fluticasone/salmeterol was more effective in reducing mortality than placebo, formoterol and fluticasone alone, and was the most effective (SUCRA=71%). NMA was conducted on CVM (37 RCTs, 55 156 patients) and the following were safest: salmeterol versus each OF placebo, tiotropium and tiotropium (Soft Mist Inhaler (SMR)); fluticasone versus tiotropium (SMR); and salmeterol/fluticasone versus tiotropium and tiotropium (SMR). Triamcinolone acetonide was the most harmful (SUCRA=81%). NMA was conducted on pneumonia occurrence (54 RCTs, 61 551 patients). 24 treatments were more harmful, including 2 that increased risk of pneumonia versus placebo; fluticasone and fluticasone/salmeterol. The most harmful agent was fluticasone/salmeterol (SUCRA=89%). NMA was conducted for arrhythmia; no statistically significant differences between agents were identified.

Conclusions Many inhaled agents are available for COPD, some are safer and more effective than others. Our results can be used by patients and physicians to tailor administration of these agents.

Protocol registration number PROSPERO # CRD42013006725.

  • Pulmonary Disease
  • Chronic Obstructive
  • Pulmonary Emphysema
  • Network Meta-analysis
  • Systematic Review

This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/

https://doi.org/10.1136/bmjopen-2015-009183

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