Clinical Edge

Summaries of Must-Read Clinical Literature, Guidelines, and FDA Actions

LAMA + LABA for Patients with Stable COPD

JAMA; 2017 Oct 3; Horita, Nagashima, et al

Inhaled long-acting muscarinic antagonists (LAMA) combined with long-acting β-agonists (LABA) may be associated with a lower risk of chronic obstructive pulmonary disease (COPD) exacerbation and with greater improvement in forced expiratory volume in the first second of expiration (FEV1), when compared with inhaled LABA combined with inhaled corticosteroids (ICS). Further, this improvement was observed without differences in the incidence of serious adverse events or quality of life, in a recent synopsis of a Cochrane review that included 11 randomized trials and 9,839 patients (74% men; 26% women) aged 61-71 years from 44 countries. Follow-up ranged from 6 to 52 weeks. Among the findings:

  • LAMA + LABA was associated with fewer patients with at least 1 COPD exacerbation events vs LABA + ICS (OR, 0.82), a larger improvement in FEV1 (mean difference, 0.08), and a lower incidence of pneumonia (OR, 0.57).
  • There was no difference between LAMA + LABA and LABA + ICS in rates of serious adverse event rates or all-cause death.
  • Between-group difference for change in St. George Respiratory Questionnaire total score from baseline was not significant.
  • More patients in LAMA + LABA group vs the LABA + ICS group experienced improvement by 4 or more points on the St. George Respiratory Questionnaire, which represents the minimal clinically important difference (OR, 1.25 [95% CI, 1.09 to 1.44]).


Horita N, Nagashima A, Kaneko T. Long-acting β-agonists (LABA) combined with long-acting muscarinic antagonists or LABA combined with inhaled corticosteroids for patients with stable COPD. JAMA. 2017;318(13):1274–1275. doi:10.1001/jama.2017.11903.


Accumulating evidence on outcomes of dual bronchodilator therapy (LAMA/LABA) vs the previous standard, LABA/ICS, represents a landmark shift in the treatment of patients with moderate-to-severe COPD. Until recently, for patients who continued to have symptoms or who had frequent exacerbations on single bronchodilator therapy, combination LABA/ICS inhalers were recommended by the GOLD guidelines and were essentially a “no-brainer” for clinicians. However, an accumulation of evidence over the last few years shows that LAMA/LABAs are more effective than LABA/ICS in COPD at decreasing the rate of exacerbations, at improving FEV1, and at improving symptoms. In addition, LABA/ICS has approximately a 40% greater incidence of development of pneumonia than LAMA/LABA combination therapy. This evidence has led to a change in the 2017 GOLD Guideline recommendations for the treatment of moderate-to-severe COPD, which now recommend LAMA/LABA, before use of ICS/LABA, for symptomatic patients with 1 or fewer non-hospitalized exacerbations in the last year if single long-acting bronchodilator therapy is not sufficient (group B). LAMA/LABA is not recommended for patients who are only mildly symptomatic, but rather, for patients who have a history of more than 1 exacerbation in the last year or 1 or more exacerbations that led to hospitalization who are not sufficiently controlled on a LAMA alone (group C). LABA/ICS is now considered an alternative for this group of patients. The guidelines recommend LAMA + LABA as the therapy of first choice for patients with a high symptom burden and who have had greater than 1 exacerbation in the last year or 1 or more exacerbations that led to hospitalization, with LABA/ICS as an alternative (group D).1—Neil Skolnik, MD

  1. Vogelmeier CF, Criner GJ, Martinez FJ, et al. Global strategy for the diagnosis, management, and prevention of chronic obstructive lung disease 2017 report. Am J Respir Crit Care Med. 2017;195(5): 557-582. doi:10.1164/rccm.201701-0218PP.